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Li J, Gao Q, Liu H, Liu S, Wang Y, Sun X, Zheng J, Yang H, Hu B. Integrating 16S rDNA sequencing analysis and targeted metabolomics to explore the mechanism of Xiexin Tang in treating atherosclerosis mice induced by high-fat diet. J Pharm Biomed Anal 2025; 259:116760. [PMID: 40014894 DOI: 10.1016/j.jpba.2025.116760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/01/2025]
Abstract
Xiexin Tang (XXT) is a classic Chinese medicine formula that can be used to treat Atherosclerosis (AS). This study aimed to investigate the mechanism by which XXT regulated AS lipid levels. Firstly, the mixture components of XXT were analyzed by High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Then, the AS model based on Apolipoprotein E knockout (ApoE-/-) mice was established. Cytokines related to lipid metabolism and bile acid metabolism were detected by Quantitative Real-time PCR (qRT-PCR). 16S rDNA gene sequencing was performed to analyze differential bacterial populations, and the mechanism of XXT regulation of bile acids affecting lipid metabolism was further explored by targeted metabolomics. Further, antibiotic-treated mice were used to investigate the role of gut microbiota in the anti-AS effect of XXT. The results showed that XXT attenuated the lipid levels and reversed the abnormal elevation of cytokines, such as hepatic lipid metabolism and inflammatory reaction in AS mice. XXT also repaired the gut barrier damage and reversed gut microbiota disorders in AS mice. Furthermore, the metabolic levels of bile acids were reshaped by XXT. Whereas, in the absence of gut microbiota, XXT failed to attenuate lipid levels and inhibit the expression of cytokines related to inflammation and bile acid metabolism in AS mice and failed to play a role in ultimately treating AS. In conclusion, XXT could effectively inhibit the inflammatory reaction and lipid accumulation in AS mice, and this effect was closely related to its remodeling of gut microbiota to regulate bile acid metabolism.
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MESH Headings
- Animals
- Drugs, Chinese Herbal/pharmacology
- Atherosclerosis/drug therapy
- Atherosclerosis/metabolism
- Mice
- Gastrointestinal Microbiome/drug effects
- Metabolomics/methods
- Lipid Metabolism/drug effects
- Diet, High-Fat/adverse effects
- Male
- Bile Acids and Salts/metabolism
- Mice, Inbred C57BL
- Chromatography, High Pressure Liquid/methods
- Tandem Mass Spectrometry/methods
- RNA, Ribosomal, 16S/genetics
- Mice, Knockout, ApoE
- Disease Models, Animal
- DNA, Ribosomal/genetics
- Cytokines/metabolism
- Mice, Knockout
- Liver/metabolism
- Liver/drug effects
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Affiliation(s)
- Junling Li
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Qianru Gao
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Hongtao Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Songlin Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Yanchun Wang
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Xiongjie Sun
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Junping Zheng
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Huabing Yang
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China.
| | - Baifei Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China.
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2
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Chong-Nguyen C, Yilmaz B, Coles B, Sokol H, MacPherson A, Siepe M, Reineke D, Mosbahi S, Tomii D, Nakase M, Atighetchi S, Ferro C, Wingert C, Gräni C, Pilgrim T, Windecker S, Blasco H, Dupuy C, Emond P, Banz Y, Losmanovà T, Döring Y, Siontis GCM. A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology. Eur J Clin Invest 2025; 55:e14381. [PMID: 39797472 DOI: 10.1111/eci.14381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025]
Abstract
BACKGROUND The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored. METHODS Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes. RESULTS Thirteen studies were included in the review: five human, three animal and five in vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E. coli. CONCLUSIONS TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.
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Affiliation(s)
| | - Bahtiyar Yilmaz
- Department of Visceral Surgery and Medicine, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Bernadette Coles
- Velindre University NHS Trust Library and Knowledge Service, Cardiff, UK
| | - Harry Sokol
- Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique-Hopitaux de Paris (APHP), Paris, France
| | - Andrew MacPherson
- Department of Visceral Surgery and Medicine, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Matthias Siepe
- Department of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - David Reineke
- Department of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Selim Mosbahi
- Department of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Daijiro Tomii
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Masaaki Nakase
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Sarah Atighetchi
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Cyril Ferro
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Christoph Wingert
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Christoph Gräni
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Thomas Pilgrim
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Stephan Windecker
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Hélène Blasco
- Faculté de médecine, Equipe neurogénétique et neurométabolomique, INSERM U930, Université François Rabelais, Tours, France
| | - Camille Dupuy
- Faculté de médecine, Equipe neurogénétique et neurométabolomique, INSERM U930, Université François Rabelais, Tours, France
| | - Patrick Emond
- Faculté de médecine, Equipe neurogénétique et neurométabolomique, INSERM U930, Université François Rabelais, Tours, France
| | - Yara Banz
- Institute of Tissue Medicine and Pathology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Tereza Losmanovà
- Institute of Tissue Medicine and Pathology, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Yvonne Döring
- Department of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität, Munich, Germany
| | - George C M Siontis
- Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland
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3
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Wang W, Zhang K, Zhang K, Wu R, Tang Y, Li Y. Gut microbiota promotes cholesterol gallstone formation through the gut-metabolism-gene axis. Microb Pathog 2025; 203:107446. [PMID: 40118296 DOI: 10.1016/j.micpath.2025.107446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 02/17/2025] [Accepted: 02/28/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND Gallstone disease, arising from the interplay between host metabolism and gut microbiota, represents a significant health concern. Dysbiosis of the gut microbiome and disruptions in circadian rhythm contribute to the pathogenesis of gallstones. This study conducted a comprehensive analysis of gut microbiota and metabolites derived from stool and serum samples of 28 patients with cholesterol gallstones (CGS) and 19 healthy controls, employing methodologies such as 16S rRNA sequencing, metaproteomics, metabolomics, and host genetic analysis. Additionally, a retrospective cohort study was utilized to assess the efficacy of probiotics or ursodeoxycholic acid (UDCA) in preventing CGS formation post-bariatric surgery. RESULTS In CGS patients, gut microbiota diversity shifted, with harmful bacteria rising and beneficial ones declining. The altered microbiota primarily affected amino acid, lipid, nucleotide, and carbohydrate metabolism. Metabolic abnormalities were noted in amino acids, glucose, lipids, and bile acids with decreased levels of ursodeoxycholic, glycosodeoxycholic, and glycolithocholic acids, and increased glycohyodeoxycholic and allocholic acids. Glutamine and alanine levels dropped, while phenylalanine and tyrosine rosed. Animal studies confirmed gene changes in gallbladder tissues related to bile acid, energy, glucose, and lipid metabolism. Importantly, UDCA and probiotics effectively reduced CGS risk post-bariatric surgery, especially when combined. CONCLUSIONS Multi-omics can clarify CGS pathology, by focusing on the gut-metabolism-gene axis, paving the way for future studies on CGS prevention and treatment through gut microbiota or metabolic interventions.
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Affiliation(s)
- Wei Wang
- Department of Interventional, The Second Hospital of Shandong University, Shandong, 250033, China
| | - Kai Zhang
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Shandong, 250033, China
| | - Kun Zhang
- Shanghai Biotree Biotech Co., Ltd., Shanghai, China
| | - Rui Wu
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Shandong, 250033, China
| | - Yu Tang
- Department of Geriatrics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
| | - Yuliang Li
- Department of Interventional, The Second Hospital of Shandong University, Shandong, 250033, China.
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4
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Dissayabutra T, Chuaypen N, Somnark P, Boonkaew B, Udomkarnjananun S, Kittiskulnam P, Charoenchittang P, Prombutara P, Tangkijvanich P. Characterization of gut dysbiosis and intestinal barrier dysfunction in patients with metabolic dysfunction-associated steatotic liver disease and chronic kidney disease: a comparative study. Sci Rep 2025; 15:15481. [PMID: 40319096 PMCID: PMC12049563 DOI: 10.1038/s41598-025-00237-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 04/25/2025] [Indexed: 05/07/2025] Open
Abstract
The mechanistic role of gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD) is increasingly recognized. Despite their close association, comparative data regarding gut dysbiosis in these disorders are limited. This study included 22 healthy controls and 180 patients (90 MASLD, 60 CKD, and 30 both diseases with sex- and age-matched). Fecal bacterial 16 S ribosomal RNA sequencing and butyryl-CoA: acetate CoA transferase (BCoAT) gene expression were analyzed. Plasma intestinal fatty acid binding protein (I-FABP), representing intestinal barrier dysfunction, was assessed using the ELISA method. Our data showed that alpha and beta diversities of gut microbiota differed between MASLD and healthy controls. However, only beta diversities were different between CKD and healthy individuals. The MASLD and CKD groups displayed fewer SCFA-producing genera, particularly Bifidobacterium, than healthy controls. Fecal BCoAT levels were inversely correlated with eGFR and I-FABP levels. Patients with CKD had significantly enriched pathogenic bacteria, reduced BCoAT, and increased I-FABP levels versus MASLD. Combining significant bacterial genera discriminated MASLD from CKD with high diagnostic accuracy (AUC of 0.90). Among patients with both diseases, gut microbial alterations showed mixed characteristics of MASLD and CKD. These data highlighted the shared and distinct gut dysbiosis and related biomarkers, which could provide a better understanding of MASLD and CKD pathogenesis.
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Affiliation(s)
- Thasinas Dissayabutra
- Metabolic Diseases in Gut and Urinary System Research Unit (MeDGURU), Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Natthaya Chuaypen
- Metabolic Diseases in Gut and Urinary System Research Unit (MeDGURU), Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pornjira Somnark
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Bootsakorn Boonkaew
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Suwasin Udomkarnjananun
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Piyawan Kittiskulnam
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Division of Internal Medicine-Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Pimpisa Charoenchittang
- Department of Computer Science, Faculty of Science, Kasetsart University, Bangkok, Thailand
- Mod Gut Co., Ltd., Bangkok, Thailand
| | - Pinidphon Prombutara
- Mod Gut Co., Ltd., Bangkok, Thailand
- Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, 10330, Thailand.
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5
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Weiting S, Chen W, Xiao L, Yanqiu H. Enhanced acid reduction in lactic acid bacteria: Breeding through irradiation-induced mutation and functional assessment. Int J Food Microbiol 2025; 435:111161. [PMID: 40157173 DOI: 10.1016/j.ijfoodmicro.2025.111161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 03/04/2025] [Accepted: 03/17/2025] [Indexed: 04/01/2025]
Abstract
High concentrations of citric acid (CA), malic acid (MA), and tartaric acids (TA) are the primary contributors to the sour taste of fruit and fruit products. However, lactic acid bacteria that are capable of efficiently degrading these organic acids are scarce. Here, three brands of sauerkraut (Xinxi, X; Yuyuan, Y; and Zou Youcai, Z) with various doses of 60Co γ-irradiation could be treated to induce mutations in their associated lactic acid bacteria and then the abilities of the resulting microbial communities to degrade CA, MA, and TA were evaluated. Sauerkraut X treated with 0.4 kGy irradiation demonstrated the greatest ability of acid reduction. Metagenomic analyses of irradiated (0.4 kGy) and non-irradiated bacterial communities from sauerkraut X revealed a slight decrease in microbial diversity due to irradiation, with a substantial decline in the relative abundance of Lactiplantibacillus xiangfangensis. Concurrently, the relative abundance of dominant acid-reducing lactic acid bacteria such as Levilactobacillus brevis, Pediococcus ethanolidurans, and Lentilactobacillus parafarraginis increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed an increase in metabolism-related genes after irradiation, indicating that fatty acid synthesis and aspartate metabolism might be key pathways involved in the enhanced degradation of CA, MA, and TA. Analysis using the Carbohydrate-Active enzymes Database (CAZy) database revealed that glycoside hydrolase (GH) and glycosyltransferase (GT) genes were the most abundant carbohydrate-associated enzyme genes in the bacterial community of sauerkraut X. This finding proved that the oligosaccharides and monosaccharides produced by GH and GT might indirectly affect rates of organic acid degradation. Three highly effective acid-reducing lactic acid bacteria from the microbial community of irradiated sauerkraut X a were isolated and identified via 16S rRNA sequencing as Pediococcus ethanolidurans, Levilactobacillus brevis, and Loigolactobacillus coryniformis. The individual strains showed degradation rates as high as 92.02 % for citric acid (Pediococcus ethanolidurans), 83.04 % for malic acid (Levilactobacillus brevis), and 90.33 % for TA (Loigolactobacillus coryniformis). This study provides a theoretical basis and technical support for the development of enhanced microbial strains that can reduce the acid content of fruit materials.
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Affiliation(s)
- Shan Weiting
- Institute of Food and Processing, Liaoning Academy of Agricultural Sciences, Shenyang 110866, People's Republic of China; Department of Food Science, Shenyang Agricultural University, Shenyang 110866, People's Republic of China
| | - Wang Chen
- Institute of Food and Processing, Liaoning Academy of Agricultural Sciences, Shenyang 110866, People's Republic of China; Department of Food Science, Shenyang Agricultural University, Shenyang 110866, People's Republic of China.
| | - Li Xiao
- Institute of Food and Processing, Liaoning Academy of Agricultural Sciences, Shenyang 110866, People's Republic of China
| | - Han Yanqiu
- Institute of Food and Processing, Liaoning Academy of Agricultural Sciences, Shenyang 110866, People's Republic of China
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6
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Quinn-Bohmann N, Carr AV, Diener C, Gibbons SM. Moving from genome-scale to community-scale metabolic models for the human gut microbiome. Nat Microbiol 2025; 10:1055-1066. [PMID: 40217129 DOI: 10.1038/s41564-025-01972-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 02/26/2025] [Indexed: 05/08/2025]
Abstract
Metabolic models of individual microorganisms or small microbial consortia have become standard research tools in the bioengineering and systems biology fields. However, extending metabolic modelling to diverse microbial communities, such as those in the human gut, remains a practical challenge from both modelling and experimental validation perspectives. In complex communities, metabolic models accounting for community dynamics, or those that consider multiple objectives, may provide optimal predictions over simpler steady-state models, but require a much higher computational cost. Here we describe some of the strengths and limitations of microbial community-scale metabolic models and argue for a robust validation framework for developing personalized, mechanistic and accurate predictions of microbial community metabolic behaviours across environmental contexts. Ultimately, quantitatively accurate microbial community-scale metabolic models could aid in the design and testing of personalized prebiotic, probiotic and dietary interventions that optimize for translationally relevant outcomes.
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Affiliation(s)
- Nick Quinn-Bohmann
- Institute for Systems Biology, Seattle, WA, USA
- Molecular Engineering Graduate Program, University of Washington, Seattle, WA, USA
| | - Alex V Carr
- Institute for Systems Biology, Seattle, WA, USA
- Molecular Engineering Graduate Program, University of Washington, Seattle, WA, USA
| | - Christian Diener
- Institute for Systems Biology, Seattle, WA, USA.
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria.
| | - Sean M Gibbons
- Institute for Systems Biology, Seattle, WA, USA.
- Molecular Engineering Graduate Program, University of Washington, Seattle, WA, USA.
- Department of Bioengineering, University of Washington, Seattle, WA, USA.
- Department of Genome Sciences, University of Washington, Seattle, WA, USA.
- eScience Institute, University of Washington, Seattle, WA, USA.
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7
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Inan S, Wilson RP, Tükel Ç. IUPHAR review: From gut to brain: The role of gut dysbiosis, bacterial amyloids, and metabolic disease in Alzheimer's disease. Pharmacol Res 2025; 215:107693. [PMID: 40086611 DOI: 10.1016/j.phrs.2025.107693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/06/2025] [Accepted: 03/07/2025] [Indexed: 03/16/2025]
Abstract
Gut microbial dysbiosis, or altered gut microbial communities, in Alzheimer's Disease suggests a pathogenic role for gut inflammation and microbial products in shaping a neuroinflammatory environment. Similarly, metabolic diseases, such as obesity and diabetes, are also associated with an increased risk of Alzheimer's Disease. As the metabolic landscape shifts during gut inflammation, and gut inflammation in turn impacts metabolic processes, we explore how these interconnected pathways may contribute to the progression of Alzheimer's Disease. Additionally, we discuss the role of bacterial amyloids produced by gut microbes, which may exacerbate amyloid aggregation in the brain and contribute to neurodegenerative processes. Furthermore, we highlight potential therapeutic strategies aimed at reducing gut inflammation, improving metabolic health, and decreasing amyloid content as a means to mitigate Alzheimer's Disease progression. These approaches, targeting the gut-brain-metabolic axis, could offer promising avenues for delaying or preventing cognitive decline in affected individuals.
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Affiliation(s)
- Saadet Inan
- Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
| | - R Paul Wilson
- Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Çagla Tükel
- Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
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8
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Nageswaran V, Carreras A, Reinshagen L, Beck KR, Steinfeldt J, Henricsson M, Ramezani Rad P, Peters L, Strässler ET, Lim J, Verhaar BJ, Döring Y, Weber C, König M, Steinhagen-Thiessen E, Demuth I, Kränkel N, Leistner DM, Potente M, Nieuwdorp M, Knaus P, Kuebler WM, Ferrell M, Nemet I, Hazen SL, Landmesser U, Bäckhed F, Haghikia A. Gut Microbial Metabolite Imidazole Propionate Impairs Endothelial Cell Function and Promotes the Development of Atherosclerosis. Arterioscler Thromb Vasc Biol 2025; 45:823-839. [PMID: 40143816 PMCID: PMC12017598 DOI: 10.1161/atvbaha.124.322346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 03/05/2025] [Indexed: 03/28/2025]
Abstract
BACKGROUND The microbially produced amino acid-derived metabolite imidazole propionate (ImP) contributes to the pathogenesis of type 2 diabetes. However, the effects of ImP on endothelial cell (EC) physiology and its role in atherosclerotic coronary artery disease are unknown. Using both human and animal model studies, we investigated the potential contributory role of ImP in the development of atherosclerosis. METHODS Plasma levels of ImP were measured in patients undergoing elective cardiac angiography (n=831) by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. Odds ratios and corresponding 95% confidence intervals for coronary artery disease were calculated based on the ImP quartiles using both univariable and multivariable logistic regression models. The effects of ImP on functional properties of ECs were assessed using HAECs (human aortic endothelial cells). In a mouse model of carotid artery injury, the impact of ImP on vascular regeneration was examined. Additionally, atheroprone Apoe-/- mice fed a high-fat diet were treated with and without ImP (800 µg), and aortic atherosclerotic lesion area was evaluated after 12 weeks. Next-generation sequencing, Western blot analysis, small interfering RNA-based gene knockdown, and tamoxifen-inducible Cre-loxP experiments were performed to investigate ImP-mediated molecular mechanisms. RESULTS Plasma ImP levels in subjects undergoing cardiac evaluation were associated with increased risk of prevalent coronary artery disease. We found that ImP dose dependently impaired migratory and angiogenic properties of human ECs and promoted an increased inflammatory response. Long-term exposure to ImP compromised the repair potential of the endothelium after an arterial insult. In atheroprone Apoe-/- (apolipoprotein E-/-) mice, ImP increased atherosclerotic lesion size. Mechanistically, ImP attenuated insulin receptor signaling by suppressing the PI3K (phosphoinositide 3-kinase)/AKT pathway leading to sustained activation of the FOXO1 (forkhead box protein O1) transcription factor. Genetic inactivation of endothelial FOXO1 signaling in ImP-treated mice enhanced the angiogenic activity and preserved the vascular repair capacity of ECs after carotid injury. CONCLUSIONS Our findings reveal a hitherto unknown role of the microbially produced histidine-derived metabolite ImP in endothelial dysfunction and atherosclerosis, suggesting that ImP metabolism is a potential therapeutic target in atherosclerotic cardiovascular disease.
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Affiliation(s)
- Vanasa Nageswaran
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- Friede Springe-Cardiovascular Prevention Center at Charité, Charité-Universitätsmedizin Berlin, Germany (V.N., J.S., E.S.-T., N.K., U.L., A.H.)
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Germany (V.N., P.K.)
- University Hospital St. Josef-Hospital Bochum, Cardiology and Rhythmology, Ruhr University Bochum, Germany (V.N., L.R., A.H.)
| | - Alba Carreras
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Sweden (A.C., K.R.B., M.H., F.B.)
| | - Leander Reinshagen
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- University Hospital St. Josef-Hospital Bochum, Cardiology and Rhythmology, Ruhr University Bochum, Germany (V.N., L.R., A.H.)
| | - Katharina R. Beck
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Sweden (A.C., K.R.B., M.H., F.B.)
| | - Jakob Steinfeldt
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- Friede Springe-Cardiovascular Prevention Center at Charité, Charité-Universitätsmedizin Berlin, Germany (V.N., J.S., E.S.-T., N.K., U.L., A.H.)
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Germany (J.S., U.L., A.H.)
| | - Marcus Henricsson
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Sweden (A.C., K.R.B., M.H., F.B.)
| | - Pegah Ramezani Rad
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
| | - Lisa Peters
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- Institute of Physiology, Charité-Universitätsmedizin Berlin, corporate member of the Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany (L.P., W.M.K.)
- Institute of Biology, Freie Universität Berlin, Germany (L.P.)
| | - Elisabeth T. Strässler
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
| | - Joseph Lim
- Angiogenesis and Metabolism Laboratory, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Germany (J.L., M.P.)
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (J.L., M.P.)
| | - Barbara J.H. Verhaar
- Department of Internal Medicine-Geriatrics, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center (UMC), the Netherlands (B.J.H.V., M.N.)
- Department of Vascular Medicine, Amsterdam UMC, the Netherlands (B.J.H.V., M.N.)
| | - Yvonne Döring
- Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilian University of Munich, Germany (Y.D., C.W.)
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Switzerland (Y.D.)
- Department for BioMedical Research (DBMR), University of Bern, Switzerland (Y.D.)
- German Center for Cardiovascular Research (DZHK), Partner Site Munich, Germany (Y.D., C.W.)
| | - Christian Weber
- Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilian University of Munich, Germany (Y.D., C.W.)
- German Center for Cardiovascular Research (DZHK), Partner Site Munich, Germany (Y.D., C.W.)
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, the Netherlands (C.W.)
- Munich Cluster for Systems Neurology, Germany (C.W.)
| | - Maximilian König
- Department of Internal Medicine D–Geriatrics, University Medicine Greifswald, Germany (M.K.)
| | - Elisabeth Steinhagen-Thiessen
- Friede Springe-Cardiovascular Prevention Center at Charité, Charité-Universitätsmedizin Berlin, Germany (V.N., J.S., E.S.-T., N.K., U.L., A.H.)
- Department of Endocrinology and Metabolic Diseases (including Division of Lipid Metabolism), Charité-Universitätsmedizin Berlin, corporate member of the Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany (E.S.-T., I.D.)
| | - Ilja Demuth
- Department of Endocrinology and Metabolic Diseases (including Division of Lipid Metabolism), Charité-Universitätsmedizin Berlin, corporate member of the Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany (E.S.-T., I.D.)
- Charité–Universitätsmedizin Berlin, Berlin Institute of Health Center for Regenerative Therapies, Germany (I.D.)
| | - Nicolle Kränkel
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- Friede Springe-Cardiovascular Prevention Center at Charité, Charité-Universitätsmedizin Berlin, Germany (V.N., J.S., E.S.-T., N.K., U.L., A.H.)
| | - David M. Leistner
- German Center for Cardiovascular Research (DZHK), Partner Site Frankfurt Rhine-Main, Germany (D.M.L.)
- Department of Medicine, Cardiology and Angiology, Goethe University Hospital, Frankfurt, Germany (D.M.L.)
| | - Michael Potente
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- Angiogenesis and Metabolism Laboratory, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Germany (J.L., M.P.)
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (J.L., M.P.)
| | - Max Nieuwdorp
- Department of Internal Medicine-Geriatrics, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center (UMC), the Netherlands (B.J.H.V., M.N.)
- Department of Vascular Medicine, Amsterdam UMC, the Netherlands (B.J.H.V., M.N.)
| | - Petra Knaus
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Germany (V.N., P.K.)
- Berlin-Brandenburg School for Regenerative Therapies, Germany (P.K.)
- International Max-Planck Research School for Biology and Computation, Berlin, Germany (P.K.)
| | - Wolfgang M. Kuebler
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- Institute of Physiology, Charité-Universitätsmedizin Berlin, corporate member of the Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany (L.P., W.M.K.)
- German Center for Lung Research (DZL), Berlin, Germany (W.M.K.)
- Keenan Research Centre for Biomedical Science at St. Michael’s, Toronto, Canada (W.M.K.)
- Departments of Surgery and Physiology, University of Toronto, Canada (W.M.K.)
| | - Marc Ferrell
- Departments of Cardiovascular and Metabolic Sciences, and Cardiovascular Medicine, Cleveland Clinic, OH (M.F., I.N., S.L.H.)
| | - Ina Nemet
- Departments of Cardiovascular and Metabolic Sciences, and Cardiovascular Medicine, Cleveland Clinic, OH (M.F., I.N., S.L.H.)
| | - Stanley L. Hazen
- Departments of Cardiovascular and Metabolic Sciences, and Cardiovascular Medicine, Cleveland Clinic, OH (M.F., I.N., S.L.H.)
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, OH (S.L.H.)
| | - Ulf Landmesser
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- Friede Springe-Cardiovascular Prevention Center at Charité, Charité-Universitätsmedizin Berlin, Germany (V.N., J.S., E.S.-T., N.K., U.L., A.H.)
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Germany (J.S., U.L., A.H.)
| | - Fredrik Bäckhed
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Sweden (A.C., K.R.B., M.H., F.B.)
- Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden (F.B.)
| | - Arash Haghikia
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin, Berlin, Germany (V.N., L.R., J.S., P.R.R., E.T.S., N.K., U.L., A.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (V.N., L.R., P.R.R., L.P., E.T.S., N.K., M.P., W.M.K., U.L., A.H.)
- Friede Springe-Cardiovascular Prevention Center at Charité, Charité-Universitätsmedizin Berlin, Germany (V.N., J.S., E.S.-T., N.K., U.L., A.H.)
- University Hospital St. Josef-Hospital Bochum, Cardiology and Rhythmology, Ruhr University Bochum, Germany (V.N., L.R., A.H.)
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Germany (J.S., U.L., A.H.)
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9
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Xin ZZ, Ma K, Che YZ, Dong JL, Xu YL, Zhang XT, Li XY, Zhang JY. Differences in Microbial Community Structure Determine the Functional Specialization of Gut Segments of Ligia exotica. Microorganisms 2025; 13:808. [PMID: 40284644 PMCID: PMC12029659 DOI: 10.3390/microorganisms13040808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 03/24/2025] [Accepted: 03/31/2025] [Indexed: 04/29/2025] Open
Abstract
Ligia feed on seashore algae and remove organic debris from the coastal zone, thereby playing an important role in the intertidal ecosystem. Nevertheless, the specific roles of distinct gut segments in the gut transit remain unclear. We collected and identified Ligia exotica specimens in the coast of Aoshanwei, Qingdao, Shandong Province, and analyzed their foreguts and hindguts for 16S rRNA, metagenomics, metabolomics, and proteomics. The concentrations of common metabolites, NO3--N and NH4+-N, and the contents of C and N were measured. The gut transit decreased the abundances of the dominant phyla Cyanobacteria but increased Proteobacteria, Firmicutes, and Actinobacteria, and Planctomycetes and Bacteroidetes remained relatively constant. The foregut gut microbiota is involved in the carbohydrates and amino acids metabolism, as well as the decomposition of polysaccharides. The hindgut gut microbiota performs a variety of functions, including carbohydrate and amino acid metabolism, fermentation, cell motility, intracellular transport, secretion, and vesicular translocation, and the decomposition of polysaccharides, disaccharides, and oligosaccharides. The results of omics analyses and molecular experiments demonstrated that the metabolic processes involving amino acids and carbohydrates are more active in the foregut, whereas the fermentation, absorption, and assimilation processes are more active in the hindgut. Taken together, the differences in microbial community structure determine the functional specialization of different gut segments, i.e., the foregut appears to be the primary site for digesting food, while the hindgut further processes and absorbs nutrients and then excretes them.
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Affiliation(s)
- Zhao-Zhe Xin
- Laboratory of Aquatic Parasitology, School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao 266237, China
| | | | | | | | | | | | | | - Jin-Yong Zhang
- Laboratory of Aquatic Parasitology, School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao 266237, China
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10
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Ahn JS, Kim S, Han EJ, Hong ST, Chung HJ. Increasing spatial working memory in mice with Akkermansia muciniphila. Commun Biol 2025; 8:546. [PMID: 40175647 PMCID: PMC11965532 DOI: 10.1038/s42003-025-07975-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 03/20/2025] [Indexed: 04/04/2025] Open
Abstract
Recent research has shown the gut microbiome's impact on memory, yet limitations hinder the identification of specific microbes linked to cognitive function. We measured spatial working memory in individual mice before and after fecal microbiota transplantation (FMT) to develop a targeted analysis that identifies memory-associated strains while minimizing host genetic effects. Transplantation of human fecal into C57BL/6 mice yielded varied outcomes: some mice showed significant improvements while others had negligible changes, indicating that these changes are due to differences in FMT colonization. Metagenomic analysis, stratified by memory performance, revealed a positive correlation between the abundance of Akkermansia muciniphila and improved memory. Moreover, administering two A. muciniphila strains, GMB 0476 and GMB 2066, to wild-type mice elevated spatial working memory via BDNF activation. Our findings indicate that specific gut microbes, particularly A. muciniphila, may modulate memory and represent potential targets for therapeutic intervention in cognitive enhancement.
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Affiliation(s)
- Ji-Seon Ahn
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea
| | - Sura Kim
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk, 54907, Republic of Korea
| | - Eui-Jeong Han
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea
| | - Seong-Tshool Hong
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk, 54907, Republic of Korea.
| | - Hea-Jong Chung
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea.
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
- Department of Bio-Analysis Science, University of Science & Technology, Daejeon, 34113, Republic of Korea.
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11
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Guo MC, Wu BC, Luo CY, Sa W, Wang L, Li ZH, Shang QH. The Effects of Fungal Pathogen Infestation on Soil Microbial Communities for Morchella sextelata Cultivation on the Qinghai-Xizang Plateau. J Fungi (Basel) 2025; 11:264. [PMID: 40278085 PMCID: PMC12029088 DOI: 10.3390/jof11040264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/14/2025] [Accepted: 03/26/2025] [Indexed: 04/26/2025] Open
Abstract
Fungi infestation as a disease has serious impacts on the cultivation of Morchella species. To investigate the effects of fungi infestation on the microbial diversity and community structure of soil when cultivating Morchella sextelata, we sampled soil samples of Morchella cultivars in the Qinghai-Xizang Platea and used metagenome sequencing technology to identify the disease fungi and analyze the differences in microbial diversity and structure between disease-infested and healthy soils. The disease fungi identified were Tricharina gilva and Peziza lohjaoensis, and the microbial diversity of T. gilva-infected soil was higher than that of healthy soil, while the diversity of P. lohjaoensis-infected soil was lower. Interestingly, whether infected with T. gilva or P. lohjaoensis, the soil microbial community was changed, and the dominant phyla and genera were different in different soil samples. When infected with P. lohjaoensis, the dominant phyla with relatively high abundances included Proteobacteria, Bacteroidetes, and Ascomycota, with average relative abundances of 44%, 18%, and 15%, respectively, and the dominant genera with high relative abundances encompassed Pseudomonadaceae, Terfezia, and Pedobacter, with average relative abundances of 8%, 9%, and 5%, respectively. Following infection with T. gilva, the dominant phyla with higher relative abundances were Proteobacteria, Acidobacteria, and Bacteroidetes, with average relative abundances of 46%, 15%, and 12%, respectively, and the dominant genera with high relative abundances included Hydrogenophaga, Sphingomonas, and Polaromonas, with average relative abundances of 9%, 3%, and 2%, respectively. Additionally, we found that lipid-metabolism-related genes were less abundant in the soil infected with P. lohjaoensis than in the other soil samples, and glycoside hydrolase diversity was lower in the soil infected with T. gilva than in other healthy soils. The results showed that the effects of different disease fungi on soil microbial communities and functional genes were different, which provided a theoretical basis for the sustainable cultivation of Morchella.
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Affiliation(s)
- Ming-Chen Guo
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810086, China; (M.-C.G.); (B.-C.W.); (W.S.); (L.W.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an 710069, China; (C.-Y.L.); (Z.-H.L.)
| | - Bo-Chun Wu
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810086, China; (M.-C.G.); (B.-C.W.); (W.S.); (L.W.)
| | - Cai-Yun Luo
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an 710069, China; (C.-Y.L.); (Z.-H.L.)
| | - Wei Sa
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810086, China; (M.-C.G.); (B.-C.W.); (W.S.); (L.W.)
| | - Le Wang
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810086, China; (M.-C.G.); (B.-C.W.); (W.S.); (L.W.)
| | - Zhong-Hu Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an 710069, China; (C.-Y.L.); (Z.-H.L.)
| | - Qian-Han Shang
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810086, China; (M.-C.G.); (B.-C.W.); (W.S.); (L.W.)
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12
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Tan F, Zheng Y, Wang C, Huang J, Liu X, Su W, Chen X, Yang Z. Effects of Chenpi Jiaosu on serum metabolites and intestinal microflora in a dyslipidemia population: a randomized controlled pilot trial. Front Endocrinol (Lausanne) 2025; 16:1552117. [PMID: 40225325 PMCID: PMC11985429 DOI: 10.3389/fendo.2025.1552117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Accepted: 02/10/2025] [Indexed: 04/15/2025] Open
Abstract
Introduction Dyslipidemia is a critical risk factor for atherosclerosis and cardiovascular/cerebrovascular events, necessitating effective long-term management. However, conventional lipid-lowering drugs such as statins and fibrates are limited by adverse effects, including hepatotoxicity and myopathy, which restrict their prolonged use. Traditional Chinese medicine (TCM) and natural health products offer potential alternatives with multi-target mechanisms and improved safety profiles. Tangerine Peel Enzyme Drink (CPJS), a fermented health product derived from tangerine peel, has demonstrated lipid-modulating properties. This study aimed to evaluate the efficacy and safety of CPJS in improving dyslipidemia and explore its underlying metabolic and microbiological mechanisms. Methods A randomized, double-blind, parallel-controlled clinical trial was conducted with 72 participants (55 completers). Participants were divided into CPJS and control groups, receiving an 8-week intervention. Primary outcomes included changes in body weight and serum triglycerides (TG), while safety was assessed via liver/kidney function, creatine kinase, blood, and urine tests. Serum metabolomics (93 differential metabolites identified) and intestinal microbiota analysis were performed to elucidate metabolic pathways and microbial shifts. KEGG enrichment analysis mapped metabolites to biological pathways, such as lipid and amino acid metabolism. Results The CPJS group exhibited significant reductions in body weight and TG levels post-intervention (p < 0.05), with no adverse effects observed in safety biomarkers. Metabolomic profiling revealed alterations in fatty acyl, glycerophospholipid, and organic acid metabolites, indicating CPJS modulates lipid metabolism and energy homeostasis. KEGG analysis linked these changes to pathways including triglyceride degradation and amino acid metabolism. Additionally, CPJS increased specific gut microbial taxa associated with lipid regulation, suggesting a microbiome-mediated mechanism. Discussion CPJS demonstrates efficacy in improving dyslipidemia through dual mechanisms: direct modulation of triglyceride metabolism and indirect regulation via gut microbiota. Its safety profile aligns with findings from natural products like Cyclocarya paliurus and tempeh, which mitigate lipid abnormalities without hepatotoxicity. The multi-target action of CPJS mirrors TCM principles, where compounds like quercetin and flavonoids in CPJS may synergistically inhibit cholesterol synthesis and enhance lipid clearance. However, further research is needed to isolate active components and validate microbial contributions. Compared to synthetic drugs, CPJS offers a safer adjunct therapy, addressing limitations of current pharmacotherapies. Future studies should explore dose-response relationships and long-term outcomes in diverse populations.
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Affiliation(s)
- Fei Tan
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuying Zheng
- Guangdong Engineering Research Center of Commercialization of Medical Institution Preparations and Traditional Chinese Medicines, Engineering Technology Research Center of Commercialization of Linnan Special Medical Institution Preparations, Experimental Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Clinical Research Academy of Chinese Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Engineering Research Center of Commercialization of Medical Institution Preparations and Traditional Chinese Medicines, Guangzhou, China
- Guangdong Engineering Technology Research Center of Commercialization of Linnan Special Medical Institution Preparations, Guangzhou, China
| | - Chengcheng Wang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiaying Huang
- The TCM Department of Longyuan Daguan Community Health Service Center, Shenzhen Longgang Orthopaedics Hospital, Shenzhen, China
| | - Xin Liu
- Production department, Guangzhou Baiyunshan Guanghua Pharmaceutical co, LTD, Guangzhou, China
| | - Weiwei Su
- School of Life Sciences, Sun Yat-sen University, Guangzhou, China
| | - Xinyan Chen
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhimin Yang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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13
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Wan J, Tian P, Liu X, Zhang H. Analysis of the Changes in Physicochemical Properties and Microbial Communities During Fermentation of Sweet Fermented Rice. Foods 2025; 14:1121. [PMID: 40238242 PMCID: PMC11988636 DOI: 10.3390/foods14071121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 03/20/2025] [Accepted: 03/21/2025] [Indexed: 04/18/2025] Open
Abstract
As a traditional rice wine, sweet fermented rice (SFR) is widely loved because of its unique flavor and high nutritional value. However, the physicochemical properties, microbial community composition, and metabolic pathway changes during the fermentation process of sweet wine have not been evaluated, and these changes can lead to unstable SFR quality. In this study, we used high-throughput sequencing technology to analyze and elucidate the dynamic changes in the microbial community, metabolic pathways, and carbohydrate enzyme functions in traditional SFR fermentation broth. The results revealed that Rhizopus abundance = 160,943.659 and Wickerhamomyces abundance = 241,660.954 were the predominant fungal genera in the fermentation process from the beginning (A0) to the end (A43) of SFR fermentation. The results of the diversity analysis revealed that the structure and composition of the microbial communities first increased but then decreased. Metabolic pathway analysis showed that energy production and conversion, carbohydrate transport, and amino acid transport were the most active metabolic pathways in fermentation. Moreover, the three primary functions of glycosyltransferases (GTs), glycoside hydrolases (GHs), and carbohydrate-binding modules (CBMs) in carbohydrate enzyme analysis were involved in the whole fermentation process. This study only provides some insight into the dynamic changes in the microbial population of SFR single samples prepared under fixed conditions. It provides a reference for optimizing the physicochemical properties of SFR fermentation broth, controlling the microbial community structure, optimizing fermentation conditions, and improving product quality.
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Affiliation(s)
| | | | | | - Hanyao Zhang
- Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China; (J.W.); (P.T.); (X.L.)
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14
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de Luca Silva B, Cendoroglo MS, Colleoni GWB. Gut Microbiota and Metabolic Biomarkers Associated With Longevity. Nutr Rev 2025:nuaf027. [PMID: 40036950 DOI: 10.1093/nutrit/nuaf027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025] Open
Abstract
The dynamic balance between pro- and anti-inflammatory networks decreases as individuals age, and intestinal dysbiosis can initiate and maintain low-grade systemic inflammation. Interactions between the microbiota and humans occur from the beginning of life and, in general, the diversity of microbiota decreases with aging. The microbiome produces different metabolites with systemic effects, including immune system regulation. This understanding will be useful in controlling inflammation and preventing metabolic changes. Therefore, this review aims to identify the main metabolites synthesized by the intestinal microbiota to be used as biomarkers associated with longevity. This is a narrative review using scientific articles published in the last 10 years in the following databases: PubMed, Scielo, and Lilacs, using the Boolean operators "and" or "or." For this review, we identified 5 articles. The main metabolites described in the literature to date are organic acids, bile acids (BAs), short-chain fatty acids, branched-chain amino acids, trimethylamine N-oxide (TMAO), and derivatives of tryptophan and indole. Among these, the only ones not yet well characterized in studies on longevity were BAs and TMAO. Glutamate and p-cresol were also highlighted in the literature, with a negative association with longevity. The others showed an association, mostly positive, and can be used as potential biomarkers correlated with healthy aging and, if better studied, as targets for intervention to promote health and well-being.
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Affiliation(s)
- Beatriz de Luca Silva
- Geriatrics and Gerontology Discipline, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP 04025-002, Brazil
| | - Maysa Seabra Cendoroglo
- Geriatrics and Gerontology Discipline, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP 04025-002, Brazil
| | - Gisele W B Colleoni
- Geriatrics and Gerontology Discipline, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP 04025-002, Brazil
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15
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Jena PK, Arditi M, Rivas MN. Gut Microbiota Alterations in Patients With Kawasaki Disease. Arterioscler Thromb Vasc Biol 2025; 45:345-358. [PMID: 39846163 PMCID: PMC11998981 DOI: 10.1161/atvbaha.124.321201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 12/09/2024] [Accepted: 01/09/2025] [Indexed: 01/24/2025]
Abstract
The intestinal microbiota influences many host biological processes, including metabolism, intestinal barrier functions, and immune responses in the gut and distant organs. Alterations in its composition have been associated with the development of inflammatory disorders and cardiovascular diseases, including Kawasaki disease (KD). KD is an acute pediatric vasculitis of unknown etiology and the leading cause of acquired heart disease in children in the United States. The presence of gastrointestinal symptoms in the acute phase of KD has been associated with an increased risk of treatment resistance and the development of coronary artery aneurysms. Studies report alterations in fecal bacterial communities of patients with KD, characterized by the blooming of pathogenic bacteria and decreased relative abundance of short-chain fatty acid-producing bacteria. However, causality and functionality cannot be established from these observational patient cohorts of KD. This highlights the need for more advanced and rigorous studies to establish causality and functionality in both experimental models of KD vasculitis and patient cohorts. Here, we review the evidence linking an altered gut microbiota composition to the development of KD, assess the potential mechanisms involved in this process, and discuss the potential therapeutic value of these observations.
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Affiliation(s)
- Prasant K. Jena
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Guerin Children’s, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Moshe Arditi
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Guerin Children’s, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Magali Noval Rivas
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Guerin Children’s, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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16
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Wiese ML, Frost F, Bahls M, von Rheinbaben S, Rühlemann M, Bang C, Franke A, Nauck M, Bülow R, Völker U, Völzke H, Ittermann T, Lerch MM, Aghdassi AA. Dietary Diversity, Rather Than Quality, Parallels a Reduction in Metabolic Syndrome and a Favorable Gut Microbiome: The Dietary Diversity Score. JOURNAL OF THE AMERICAN NUTRITION ASSOCIATION 2025; 44:256-266. [PMID: 39556796 DOI: 10.1080/27697061.2024.2423775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/24/2024] [Accepted: 10/28/2024] [Indexed: 11/20/2024]
Abstract
OBJECTIVE Diet plays a crucial role in the development of metabolic syndrome (MetS). While dietary recommendations primarily focus on quality of food intake, the relevance and mechanisms of dietary diversity for the prevention of obesity and metabolic diseases are unclear. Here, we investigate the respective associations of dietary diversity and quality with MetS and gut microbiota composition. METHODS Pooled data from 2 independent population-based cohorts of the Study of Health in Pomerania (n = 6753) were used. Based on a validated food frequency questionnaire a novel dietary diversity score (DDS) and an established dietary quality score (DQS) were calculated. Both were correlated with anthropometric data and clinical components of MetS as well as with intestinal microbial composition (16S rRNA gene sequencing). RESULTS DDS was associated with a healthier metabolic phenotype and lower MetS risk in both cross-sectional (odds ratio [OR], 0.90; 95% CI, 0.82-0.93; p < 0.001) and longitudinal analyses of 5-year follow-up data (OR, 0.89; 95% CI, 0.79-0.99; p = 0.029). In contrast, there were hardly any favorable associations between DQS and MetS, neither cross-sectionally nor longitudinally. DDS explained 42.6% more beta diversity variation in gut microbiota than DQS and was linked to a more favorable microbial composition (e.g., less Escherichia/Shigella [q = 0.00576] and greater Ruminococcaceae [q = 0.01263] abundance). CONCLUSIONS Dietary diversity, as determined by the novel DDS, reduces MetS risk, whereas dietary quality was less important in that regard. Greater dietary diversity was paralleled by greater microbiota diversity and a healthier gut microbiome. Future dietary recommendations should emphasize dietary diversity rather than absolute consumption of nutritional components.
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Affiliation(s)
- Mats L Wiese
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Fabian Frost
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Martin Bahls
- Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
- German Centre for Cardiovascular Research (DZHK), Greifswald, Germany
| | | | - Malte Rühlemann
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Corinna Bang
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Matthias Nauck
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Robin Bülow
- Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
| | - Uwe Völker
- Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
| | - Henry Völzke
- German Centre for Cardiovascular Research (DZHK), Greifswald, Germany
- Institute for Community Medicine, University of Greifswald, Greifswald, Germany
| | - Till Ittermann
- German Centre for Cardiovascular Research (DZHK), Greifswald, Germany
- Institute for Community Medicine, University of Greifswald, Greifswald, Germany
| | - Markus M Lerch
- University Hospital, Ludwig Maximilians University Munich, Munich, Germany
| | - Ali A Aghdassi
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
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17
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Zhang L, Yin Y, Jin S. Gut microbial metabolites: The bridge connecting diet and atherosclerosis, and next-generation targets for dietary interventions. Microbiol Res 2025; 292:128037. [PMID: 39752807 DOI: 10.1016/j.micres.2024.128037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/05/2024] [Accepted: 12/19/2024] [Indexed: 01/19/2025]
Abstract
Mounting evidence indicates that gut microbial metabolites are central hubs linking the gut microbiota to atherosclerosis (AS). Gut microbiota enriched with pathobiont bacteria responsible for producing metabolites like trimethylamine N-oxide and phenylacetylglutamine are related to an increased risk of cardiovascular events. Furthermore, gut microbiota enriched with bacteria responsible for producing short-chain fatty acids, indole, and its derivatives, such as indole-3-propionic acid, have demonstrated AS-protective effects. This study described AS-related gut microbial composition and how microbial metabolites affect AS. Summary findings revealed gut microbiota and their metabolites-targeted diets could benefit AS treatment. In conclusion, dietary interventions centered on the gut microbiota represent a promising strategy for AS treatment, and understanding diet-microbiota interactions could potentially be devoted to developing novel anti-AS therapies.
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Affiliation(s)
- Liyin Zhang
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, Hubei 430077, China
| | - Yao Yin
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, Hubei 430077, China
| | - Si Jin
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, Hubei 430077, China.
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18
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Li S, Liu Y, Yang X, Yang Y, Peng J, Xu Y, Wei J. Spatiotemporal composition and diversity of endophyte communities in Dracaena cambodiana on Hainan Island. Front Microbiol 2025; 16:1540669. [PMID: 40092035 PMCID: PMC11906717 DOI: 10.3389/fmicb.2025.1540669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 02/14/2025] [Indexed: 03/19/2025] Open
Abstract
Introduction Dracaena cambodiana produces a red resin known as Dragon's blood, which is used worldwide in traditional medicine and as a dye. The role of endophytes in the resin-formation process remains underexplored. Understanding the endophyte communities and their functional roles in resin production could enable the development of efficient induction techniques for resin production. Methods In this study, ITS and metagenomic sequencing analyzed endophyte communities' characteristics and functional traits in different tissues and D. cambodiana across multiple wild populations on Hainan Island. Results We identified distinct fungal genera that were dominant in different tissues. Following injury, we observed significant changes in the expression of endophytic fungal genes. These changes indicated that metabolic pathways associated with resin metabolism, sucrose metabolism, signal transduction, and phenylalanine metabolism were likely involved in resin formation. Additionally, several glycosylation gene families were upregulated in the post-injury endophytic communities, which suggests a role in flavonoid transport and the reduction of autotoxic effects. Discussion Our results suggest that endophytes play a vital role in the resin-formation process of D. cambodiana. Isolating specific endophytes or using synthetic communities could potentially improve resin yields and avoid pathogenic fungi, ensuring safety. The findings from this study provide a theoretical basis for the development of high-efficiency resin induction techniques by targeting the dynamic changes in endophyte communities across tissues, regions, and resin formation stages.
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Affiliation(s)
- Sipeng Li
- Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine and Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou, China
| | - Yang Liu
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education and National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Yang
- Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine and Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou, China
| | - Yun Yang
- Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine and Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou, China
| | - Junxiang Peng
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education and National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanhong Xu
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education and National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianhe Wei
- Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine and Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education and National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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19
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Ma ZF, Fu C, Lee YY. The Modulatory Role of Bioactive Compounds in Functional Foods on Inflammation and Metabolic Pathways in Chronic Diseases. Foods 2025; 14:821. [PMID: 40077524 PMCID: PMC11899172 DOI: 10.3390/foods14050821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 02/24/2025] [Accepted: 02/24/2025] [Indexed: 03/14/2025] Open
Abstract
Chronic diseases are major contributors to global morbidity and mortality. More than 70% of deaths worldwide are caused by chronic diseases, including cardiovascular diseases (CVDs), obesity, type 2 diabetes, and cancer. These diseases are characterised by chronic low-grade inflammation and metabolic dysregulation. Incorporating functional foods into daily diet has been suggested as a complementary strategy to promote health and lower the risk of non-communicable diseases. Functional foods, known as foods that confer health benefits beyond basic nutrition, have been reported to exhibit preventive and therapeutic benefits such as anti-inflammatory properties for human health. Therefore, the aim of this state-of-the-art review will synthesise the findings from recent and high-quality studies that investigated the modulatory role of some commonly reported bioactive active compounds, such as polyphenols, omega-3 fatty acids, probiotics, and prebiotics, in inflammation and metabolic pathways.
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Affiliation(s)
- Zheng Feei Ma
- Centre for Public Health and Wellbeing, School of Health and Social Wellbeing, College of Health, Science and Society, University of the West of England, Bristol BS16 1QY, UK
| | - Caili Fu
- Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu 15200, Malaysia
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20
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Alharbi SM, Al-Sulami N, Al-Amrah H, Anwar Y, Gadah OA, Bahamdain LA, Al-Matary M, Alamri AM, Bahieldin A. Metagenomic Characterization of the Maerua crassifolia Soil Rhizosphere: Uncovering Microbial Networks for Nutrient Acquisition and Plant Resilience in Arid Ecosystems. Genes (Basel) 2025; 16:285. [PMID: 40149437 PMCID: PMC11942469 DOI: 10.3390/genes16030285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/04/2025] [Accepted: 02/20/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives:Maerua crassifolia, a threatened medicinal species endemic to drylands, exhibits a pronounced drought sensitivity. Despite the critical role of microorganisms, particularly bacteria and fungi, the microbial consortia in M. crassifolia's rhizosphere remain underexplored. Methods: Metagenomic whole genome shotgun sequencing (WGS) was employed to elucidate the taxonomic composition of bacterial and fungal communities inhabiting the soil rhizosphere of M. crassifolia. Results: The data revealed a marked predominance of bacterial genomes relative to fungal communities, as evidenced by non-redundant gene analysis. Notably, arbuscular mycorrhizal fungi (AMF), specifically Rhizophagus clarus, Rhizophagus irregularis and Funneliformis geosporum, are key rhizosphere colonizers. This study confirmed the presence of phosphate-solubilizing bacteria (PSB), such as Sphingomonas spp., Cyanobacteria and Pseudomonadota, underscoring the critical role of these microorganisms in the phosphorus cycle. Additionally, the study uncovered the presence of previously uncharacterized species within the phylum Actinobacteria, as well as unidentified taxa from the Betaproteobacteria, Gemmatimonadota and Chloroflexota phyla, which may represent novel microbial taxa with potential plant growth-promoting properties. Conclusions: Findings suggest a complex, symbiotic network where AMF facilitate phosphorus uptake through plant-root interactions. In a tripartite symbiosis, PSB enhance inorganic phosphorus solubilization, increasing bioavailability, which AMF assimilate and deliver to plant roots, optimizing nutrition. This bacterial-fungal interplay is essential for plant resilience in arid environments. Future investigations should prioritize the isolation and characterization of underexplored microbial taxa residing in the rhizosphere of M. crassifolia, with particular emphasis on members of the Actinobacteria, Betaproteobacteria, Gemmatimonadota and Chloroflexota phyla to uncover their roles in nutrient acquisition and sustainability.
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Affiliation(s)
| | - Nadiah Al-Sulami
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia (H.A.-A.); (Y.A.); (M.A.-M.); (A.M.A.)
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21
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Ohlsson C, Lawenius L, Jiang Y, Horkeby K, Wu J, Nilsson KH, Koskela A, Tuukkanen J, Movérare-Skrtic S, Henning P, Sjögren K. The beneficial effects of a probiotic mix on bone and lean mass are dependent on the diet in female mice. Sci Rep 2025; 15:6182. [PMID: 39979617 PMCID: PMC11842756 DOI: 10.1038/s41598-025-91056-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/18/2025] [Indexed: 02/22/2025] Open
Abstract
Bone mass and lean mass decrease with age and these changes are associated with increased fracture risk and sarcopenia. Previous studies demonstrated that a probiotic mixture of Lacticaseibacillus paracasei DSM13434, Lactiplantibacillus plantarum DSM 15312 and DSM 15313 (L. Mix) prevents bone loss in ovariectomized (ovx) female mice. The purpose of the present study is to test if the beneficial effect of L. Mix is modified by the diet. Female mice were fed either a high-fat (HFD, 60% kcal from fat) or a low-fat (LFD, 10% kcal from fat) diet and subjected to either sham or ovx surgery and treated with L. Mix for 12 weeks. L. Mix treatment increased total body bone mineral density (p ≤ 0.01), by increasing cortical bone area, and total body lean mass (p = 0.035) in mice on LFD but not in mice on HFD. Metagenome sequencing of cecal content showed that L. Mix treatment increased the relative abundance of Lacticaseibacillus paracasei and, Lactiplantibacillus plantarum, demonstrating successful treatment. In addition, the probiotic treatment affected the overall gut microbiota composition and functionality. These findings demonstrate that the L. Mix in combination with a healthy diet is beneficial for musculoskeletal health in female mice.
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Affiliation(s)
- Claes Ohlsson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lina Lawenius
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Yiwen Jiang
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Karin Horkeby
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jianyao Wu
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Karin H Nilsson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Antti Koskela
- Department of Anatomy and Cell Biology, Faculty of Medicine, Translational Medicine Research Unit, University of Oulu, Oulu, Finland
| | - Juha Tuukkanen
- Department of Anatomy and Cell Biology, Faculty of Medicine, Translational Medicine Research Unit, University of Oulu, Oulu, Finland
| | - Sofia Movérare-Skrtic
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Petra Henning
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Klara Sjögren
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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22
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Sun T, Song B, Li B. Gut microbiota and atrial cardiomyopathy. Front Cardiovasc Med 2025; 12:1541278. [PMID: 39968343 PMCID: PMC11832500 DOI: 10.3389/fcvm.2025.1541278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 01/20/2025] [Indexed: 02/20/2025] Open
Abstract
Atrial cardiomyopathy is a multifaceted heart disease characterized by structural and functional abnormalities of the atria and is closely associated with atrial fibrillation and its complications. Its etiology involves a number of factors, including genetic, infectious, immunologic, and metabolic factors. Recent research has highlighted the critical role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, and this is consistent with the gut-heart axis having major implications for cardiac health. The aim of this work is to bridge the knowledge gap regarding the interactions between the gut microbiota and atrial cardiomyopathy, with a particular focus on elucidating the mechanisms by which gut dysbiosis may induce atrial remodeling and dysfunction. This article provides an overview of the role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, including changes in the composition of the gut microbiota and the effects of its metabolites. We also discuss how diet and exercise affect atrial cardiomyopathy by influencing the gut microbiota, as well as possible future therapeutic approaches targeting the gut-heart axis. A healthy gut microbiota can prevent disease, but ecological dysbiosis can lead to a variety of symptoms, including the induction of heart disease. We focus on the pathophysiological aspects of atrial cardiomyopathy, the impact of gut microbiota dysbiosis on atrial structure and function, and therapeutic strategies exploring modulation of the microbiota for the treatment of atrial cardiomyopathy. Finally, we discuss the role of gut microbiota in the treatment of atrial cardiomyopathy, including fecal microbiota transplantation and oral probiotics or prebiotics. Our study highlights the importance of gut microbiota homeostasis for cardiovascular health and suggests that targeted interventions on the gut microbiota may pave the way for innovative preventive and therapeutic strategies targeting atrial cardiomyopathy.
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Affiliation(s)
- Tingting Sun
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
| | - Beibei Song
- Department of Cardiology, Zibo Central Hospital, Zibo, China
| | - Bo Li
- Department of Cardiology, Zibo Central Hospital, Zibo, China
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23
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Chu G, Gao C, Wang Q, Zhang W, Tian T, Chen W, Gao M. Effect of light intensity on nitrogen removal, enzymatic activity and metabolic pathway of algal-bacterial symbiosis in rotating biological contactor treating mariculture wastewater. BIORESOURCE TECHNOLOGY 2025; 417:131872. [PMID: 39581480 DOI: 10.1016/j.biortech.2024.131872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 11/18/2024] [Accepted: 11/22/2024] [Indexed: 11/26/2024]
Abstract
An algal-bacterial symbiosis (ABS) system was developed on a rotating biological contactor treating mariculture wastewater, and its nitrogen removal, enzymatic activity and metabolic pathways were investigated under different light intensities. The nitrogen removal efficiency increased when light intensities ranged from 20 to 80 μE/(m2·s) but declined under 100 μE/(m2·s). Higher enzymatic activities under 80 μE/(m2·s) facilitated nitrogen conversion, light utilization, ATP supply and photosynthesis. Reactive oxygen species accumulation activated antioxidant pathways under 20 and 100 μE/(m2·s). Functional bacteria including Sedimentitalea, Thauera and Dechloromonas as well as Chlorella sorokinian, Dunaliella, Pleurosira laevis and Microcystis were enriched under 80 μE/(m2·s). Abundant photosynthesis-related genes (petC, Lca3/4 and atpH/A) supported energy supply and electron transport. Conversely, lower proportions of IDH3, gltB, and acnA/B under 20 and 100 μE/(m2·s) hindered tricarboxylic acid cycle, reducing NADPH and energy production. These results enhance the understanding on the effect of light intensity on ABS system treating mariculture wastewater.
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Affiliation(s)
- Guangyu Chu
- Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China; Shandong Provincial Key Laboratory of Marine Environment and Geological Engineering, Ocean University of China, Qingdao 266100, China; College of Environmental Science and Engineering, Ocean University of China, Qingdao 266100, China
| | - Chang Gao
- Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China; Shandong Provincial Key Laboratory of Marine Environment and Geological Engineering, Ocean University of China, Qingdao 266100, China
| | - Qianzhi Wang
- Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China; College of Environmental Science and Engineering, Ocean University of China, Qingdao 266100, China
| | - Wenchen Zhang
- Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China
| | - Taotao Tian
- Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China
| | - Wenzheng Chen
- Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China
| | - Mengchun Gao
- Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China; College of Environmental Science and Engineering, Ocean University of China, Qingdao 266100, China.
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24
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Cámara-Martos F, Bolívar A, Rabasco-Vílchez L, Lafont-Déniz F, Luque-Ojeda JL, Pérez-Rodríguez F. Exploring the bioaccessibility, in vitro colonic fermentation, and the impact on the intestinal microbiota of allyl-and benzyl-isothiocyanate from white and Ethiopian mustard. Food Res Int 2025; 203:115781. [PMID: 40022320 DOI: 10.1016/j.foodres.2025.115781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/28/2024] [Accepted: 01/16/2025] [Indexed: 03/03/2025]
Abstract
The aim of this research was to study the formation and bioaccessibility of allyl- and benzyl-isothiocyanate (ITC) resulting from the gastrointestinal digestion (small and large intestine) of green parts from Ethiopian and white mustard. In addition, a GC-MS methodology was validated to determine these compounds in bioaccessible and non-bioaccessible fraction. Plant clumps were divided into two batches: fresh and freeze-dried samples. ITC bioaccessibility was low in the small intestine, with values ranged between 11 and 53 % and mean values of 26 %. These results are in agreement with the fact that ITCs are poorly water-soluble compounds. Bioaccessibility values for lyophilised samples were lower than those obtained in fresh samples. This could be due to the degradation of the precursor glucosinolates (sinigrin and glucotropaeolin respectively). The simulation of the colonic fermentation reduced allyl - and benzyl - ITC levels from the non-bioaccessible fraction of Ethiopian and white mustard (values between 0.009 and 0.087 mg/g). In both cases, ITCs concentration dropped dramatically, i.e. with a ten-fold reduction. Nevertheless, this result does not necessarily indicate that ITCs have not been produced in the large intestine. Bacterial microbiota plays a key role in generating ITCs; however, ITCs are not always the final products of this process. The metagenomic analysis of colonic samples revealed that ITCs and cruciferous matrix significantly influenced the composition of gut microbiota, inhibiting potentially pathogenic bacteria such as Enterobacter and Klebsiella, while promoting beneficial bacteria such as Bifidobacterium, Faecalibacterium, Blautia, and Ruminococcus. Interestingly, ITCs-rich environments selected bacterial species (i.e. Enterobacter ludwigii) and promoted metabolic pathways involved in glucosinolate/ITCs metabolism.
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Affiliation(s)
- F Cámara-Martos
- Departamento de Bromatología y Tecnología de los Alimentos, Universidad de Córdoba, Campus Universitario de Rabanales, Edificio C-1 14014 Córdoba, Spain.
| | - A Bolívar
- Departamento de Bromatología y Tecnología de los Alimentos, Universidad de Córdoba, Campus Universitario de Rabanales, Edificio C-1 14014 Córdoba, Spain; UIC Zoonosis y Enfermedades Emergentes ENZOEM, ceiA3, Universidad de Córdoba 14014 Córdoba, Spain
| | - L Rabasco-Vílchez
- Departamento de Bromatología y Tecnología de los Alimentos, Universidad de Córdoba, Campus Universitario de Rabanales, Edificio C-1 14014 Córdoba, Spain; UIC Zoonosis y Enfermedades Emergentes ENZOEM, ceiA3, Universidad de Córdoba 14014 Córdoba, Spain
| | - F Lafont-Déniz
- Servicios Centrales de Apoyo a la Investigación (SCAI), Universidad de Córdoba, Campus Universitario de Rabanales, Edificio Ramón y Cajal 14014 Córdoba, Spain
| | - J L Luque-Ojeda
- Estación Experimental del Zaidín (EEZ - CSIC), C/Prof. Albareda 1 18008 Granada, Spain
| | - F Pérez-Rodríguez
- Departamento de Bromatología y Tecnología de los Alimentos, Universidad de Córdoba, Campus Universitario de Rabanales, Edificio C-1 14014 Córdoba, Spain; UIC Zoonosis y Enfermedades Emergentes ENZOEM, ceiA3, Universidad de Córdoba 14014 Córdoba, Spain
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25
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Babalola OO, Enagbonma BJ. Dataset of shotgun metagenomic evaluation of Sorghum bicolor rhizosphere microbiome in soils preceded by Glycine max. Data Brief 2025; 58:111270. [PMID: 39906131 PMCID: PMC11791250 DOI: 10.1016/j.dib.2025.111270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/20/2024] [Accepted: 12/30/2024] [Indexed: 02/06/2025] Open
Abstract
The dataset presents the microbial diversity, community structure, and functional potential of the rhizosphere microbiome associated with Sorghum bicolor in response to crop rotation involving a Glycine max precursor. Soil samples were collected from the rhizospheres of two Sorghum bicolor cultivars, Avenger and NS55, cultivated in soils previously used for Glycine max and cultivated in soils that have not previously been used for Glycine max cultivation, as follows: i) Sorghum bicolor Avenger (SA1, SA2, and SA3) cultivated in soils previously used for Glycine max, ii) Sorghum bicolor NS55 (SN1, SN2, and SN3) grown in soils that had been cultivated with Glycine max, iii) Sorghum bicolor Avenger (RA1, RA2, and RA3) cultivated in soils not previously used for Glycine max, iv) Sorghum bicolor NS55 (RN1, RN2, and RN3) grown in soils not previously cultivated with Glycine max. Thereafter, the shotgun sequencing was done to assess the microbial composition and functional genes from the extracted DNA. The effective metagenome after QC of the twelve samples include SA1 (99.72%), SA2 (99.50%), SA3 (99.68%), SN1 (99.75%), SN2 (99.76%), SN3 (99.70%), RA1 (99.72%), RA2 (99.77%), RN3 (99.72%), RN1 (99.67%), RN2 (99.68%), and RN3 (99.54%). Information from the metagenome sequences is accessible under the bioproject numbers PRJNA1166458 (SA1, SA2, and SA3), PRJNA1166463 (SN1, SN2, and SN3), PRJNA1166623 (RA1, RA2, and RA3), PRJNA1166627 (RN1, RN2 and RN3). Actinomycetota and Function unknown dominated the microbiomes across all cropping systems. The insights gained from this dataset hold promise for advancing sustainable agricultural practices, particularly through optimizing crop rotations, developing microbial bioinoculants, and enhancing soil health. Furthermore, the functional data and the function unknown from this dataset could enrich our understanding of microbial roles in nutrient cycling, plant growth promotion, and stress mitigation, which are critical for addressing challenges in food security and environmental sustainability.
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Affiliation(s)
- Olubukola Oluranti Babalola
- Food Security and Safety Focus Area, Faculty of Natural and Agricultural Sciences, North-West University, Private Mail Bag X2046, Mmabatho 2735, South Africa
| | - Ben Jesuorsemwen Enagbonma
- Food Security and Safety Focus Area, Faculty of Natural and Agricultural Sciences, North-West University, Private Mail Bag X2046, Mmabatho 2735, South Africa
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26
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Khuu MP, Paeslack N, Dremova O, Benakis C, Kiouptsi K, Reinhardt C. The gut microbiota in thrombosis. Nat Rev Cardiol 2025; 22:121-137. [PMID: 39289543 DOI: 10.1038/s41569-024-01070-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2024] [Indexed: 09/19/2024]
Abstract
The gut microbiota has emerged as an environmental risk factor that affects thrombotic phenotypes in several cardiovascular diseases. Evidence includes the identification of marker species by sequencing studies of the gut microbiomes of patients with thrombotic disease, the influence of antithrombotic therapies on gut microbial diversity, and preclinical studies in mouse models of thrombosis that have demonstrated the functional effects of the gut microbiota on vascular inflammatory phenotypes and thrombus formation. In addition to impaired gut barrier function promoting low-grade inflammation, gut microbiota-derived metabolites have been shown to act on vascular cell types and promote thrombus formation. Therefore, these meta-organismal pathways that link the metabolic capacities of gut microorganisms with host immune functions have emerged as potential diagnostic markers and novel drug targets. In this Review, we discuss the link between the gut microbiota, its metabolites and thromboembolic diseases.
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Affiliation(s)
- My Phung Khuu
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Nadja Paeslack
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Olga Dremova
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Corinne Benakis
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
| | - Klytaimnistra Kiouptsi
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
| | - Christoph Reinhardt
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.
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27
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Giakomidi D, Ishola A, Nus M. Targeting gut microbiota to regulate the adaptive immune response in atherosclerosis. Front Cardiovasc Med 2025; 12:1502124. [PMID: 39957996 PMCID: PMC11825770 DOI: 10.3389/fcvm.2025.1502124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 01/20/2025] [Indexed: 02/18/2025] Open
Abstract
Atherosclerosis, the leading cause of death worldwide, is a chronic inflammatory disease leading to the accumulation of lipid-rich plaques in the intima of large and medium-sized arteries. Accumulating evidence indicates the important regulatory role of the adaptive immune system in atherosclerosis during all stages of the disease. The gut microbiome has also become a key regulator of atherosclerosis and immunomodulation. Whilst existing research extensively explores the impact of the microbiome on the innate immune system, only a handful of studies have explored the regulatory capacity of the microbiome on the adaptive immune system to modulate atherogenesis. Building on these concepts and the pitfalls on the gut microbiota and adaptive immune response interaction, this review explores potential strategies to therapeutically target the microbiome, including the use of prebiotics and vaccinations, which could influence the adaptive immune response and consequently plaque composition and development.
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Affiliation(s)
- Despina Giakomidi
- Cardiovascular Division, Department of Medicine, Heart and Lung Research Institute (HLRI), University of Cambridge, Cambridge, United Kingdom
- British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, United Kingdom
| | - Ayoola Ishola
- Cardiovascular Division, Department of Medicine, Heart and Lung Research Institute (HLRI), University of Cambridge, Cambridge, United Kingdom
| | - Meritxell Nus
- Cardiovascular Division, Department of Medicine, Heart and Lung Research Institute (HLRI), University of Cambridge, Cambridge, United Kingdom
- British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, United Kingdom
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28
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Leon-Gomez P, Romero VI. Human papillomavirus, vaginal microbiota and metagenomics: the interplay between development and progression of cervical cancer. Front Microbiol 2025; 15:1515258. [PMID: 39911706 PMCID: PMC11794528 DOI: 10.3389/fmicb.2024.1515258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 12/26/2024] [Indexed: 02/07/2025] Open
Abstract
Persistent infection with oncogenic human papillomavirus (HPV) types, such as HPV 16 or 18, is a major factor in cervical cancer development. However, only a small percentage of infected women develop cancer, indicating that other factors are involved. Emerging evidence links vaginal microbiota with HPV persistence and cancer progression. Alterations in microbial composition, function, and metabolic pathways may contribute to this process. Despite the potential of metagenomics to explore these interactions, studies on the vaginal microbiota's role in cervical cancer are limited. This review systematically examines the relationship between cervical microbiota, HPV, and cervical cancer by analyzing studies from PubMed, EBSCO, and Scopus. We highlight how microbial diversity influences HPV persistence and cancer progression, noting that healthy women typically have lower microbiota diversity and higher Lactobacillus abundance compared to HPV-infected women, who exhibit increased Gardenella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., associated with dysbiosis. We discuss how microbial diversity is associated with HPV persistence and cancer progression, noting that studies suggest healthy women typically have lower microbiota diversity and higher Lactobacillus abundance, while HPV-infected women exhibit increased Gardnerella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., indicative of dysbiosis. Potential markers such as Gardnerella and Prevotella have been identified as potential microbiome biomarkers associated with HPV infection and cervical cancer progression. The review also discusses microbiome-related gene expression changes in cervical cancer patients. However, further research is needed to validate these findings and explore additional microbiome alterations in cancer progression.
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Affiliation(s)
- Paul Leon-Gomez
- College of Biological and Environmental Sciences, Universidad San Francisco de Quito, Quito, Ecuador
| | - Vanessa I. Romero
- College of Biological and Environmental Sciences, Universidad San Francisco de Quito, Quito, Ecuador
- School of Medicine, Universidad San Francisco de Quito, Quito, Ecuador
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29
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Wang Y, Li R, Wang C, Sun T, Zhang H, Zhao F, Liu J, Hao Y, Xie X. The intestinal microbial community and function of Riptortus pedestris at different developmental stages and its effects on development. Front Microbiol 2025; 16:1517280. [PMID: 39935633 PMCID: PMC11813222 DOI: 10.3389/fmicb.2025.1517280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/09/2025] [Indexed: 02/13/2025] Open
Abstract
Introduction Riptortus pedestris is a destructive pest that threatens multiple leguminous crops in China. The intestinal microbiota plays a crucial role in the growth and reproduction of host insects. However, the composition and function of the gut microbiota at different developmental stages remain unclear. Methods Here, metagenomic sequencing was performed to clarify the gut microbial diversity and function in 2nd-, 3rd-, 4th-, and 5th- instar nymphs (2 N-5 N) and female adults (FAs) of R. pedestris and the effects of vital gut bacteria on development was detected. The gut bacteria have the stage specificity, indicating their function in the development of R. pedestris. Results Enterococcus and Caballerronia were the predominant bacteria present during the development of the 2 N-FAs. In addition, the microbial abundances in the 3 N and 4 N guts were significantly greater than those in the others guts. Furthermore, 5 N harbored the abundant microbiota Burkholderia-Paraburkholderia-Caballeronia. The metabolic pathways were significantly enriched from 2 N to FAs. Carbohydrate metabolism, including glycoside hydrolases (GHs) and glycosyl transferases (GTs), occurs throughout the entire developmental stage. Many antibiotic resistance genes (ARGs) were detected from 2 N to FAs. The bacteria from Pseudomonadota and Bacillota presented a broad spectrum of antibiotic resistance. Excitingly, Burkholderia bacteria eliminated by antibiotic treatment were unable to molt normally, and their lifespan was shortened in nymphs, indicating that the gut microbiota had a significant effect on nymph development. Conclusion In summary, our results, for the first time, systematically illustrate the abundance and function across the gut microbiota from the different developmental stages of R. pedestris and demonstrate that the genera Burkholderia are crucial during the development of R. pedestris. This study provides the basis for stinkbug management strategies that focus on the pivotal gut microbiota.
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Affiliation(s)
- Yanbin Wang
- Institute of Wheat Research, Shanxi Agricultural University, Linfen, Shanxi, China
| | - Rong Li
- Institute of Wheat Research, Shanxi Agricultural University, Linfen, Shanxi, China
| | - Chunjing Wang
- College of Plant Protection, Shanxi Agricultural University, Taigu, Shanxi, China
| | - Ting Sun
- College of Plant Protection, Shanxi Agricultural University, Taigu, Shanxi, China
| | - Hongjuan Zhang
- Institute of Wheat Research, Shanxi Agricultural University, Linfen, Shanxi, China
| | - Fang Zhao
- Institute of Wheat Research, Shanxi Agricultural University, Linfen, Shanxi, China
| | - Jiehui Liu
- Institute of Wheat Research, Shanxi Agricultural University, Linfen, Shanxi, China
| | - Yuqiong Hao
- Key Laboratory of Sustainable Dryland Agriculture (Coconstruction by Ministry and Province) Ministry of Agriculture and Rural Affairs, Institute of Wheat Research, Shanxi Agricultural University, Linfen, Shanxi, China
| | - Xiansheng Xie
- Institute of Wheat Research, Shanxi Agricultural University, Linfen, Shanxi, China
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30
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Butkovich LV, Vining OB, O'Malley MA. New approaches to secondary metabolite discovery from anaerobic gut microbes. Appl Microbiol Biotechnol 2025; 109:12. [PMID: 39831966 PMCID: PMC11747023 DOI: 10.1007/s00253-024-13393-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 01/22/2025]
Abstract
The animal gut microbiome is a complex system of diverse, predominantly anaerobic microbiota with secondary metabolite potential. These metabolites likely play roles in shaping microbial community membership and influencing animal host health. As such, novel secondary metabolites from gut microbes hold significant biotechnological and therapeutic interest. Despite their potential, gut microbes are largely untapped for secondary metabolites, with gut fungi and obligate anaerobes being particularly under-explored. To advance understanding of these metabolites, culture-based and (meta)genome-based approaches are essential. Culture-based approaches enable isolation, cultivation, and direct study of gut microbes, and (meta)genome-based approaches utilize in silico tools to mine biosynthetic gene clusters (BGCs) from microbes that have not yet been successfully cultured. In this mini-review, we highlight recent innovations in this area, including anaerobic biofoundries like ExFAB, the NSF BioFoundry for Extreme & Exceptional Fungi, Archaea, and Bacteria. These facilities enable high-throughput workflows to study oxygen-sensitive microbes and biosynthetic machinery. Such recent advances promise to improve our understanding of the gut microbiome and its secondary metabolism. KEY POINTS: • Gut microbial secondary metabolites have therapeutic and biotechnological potential • Culture- and (meta)genome-based workflows drive gut anaerobe metabolite discovery • Anaerobic biofoundries enable high-throughput workflows for metabolite discovery.
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Affiliation(s)
- Lazarina V Butkovich
- Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA
| | - Oliver B Vining
- Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA
| | - Michelle A O'Malley
- Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
- U.S. Department of Energy Joint Genome Institute (JGI), Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
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31
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Chong S, Lin M, Chong D, Jensen S, Lau NS. A systematic review on gut microbiota in type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2025; 15:1486793. [PMID: 39897957 PMCID: PMC11782031 DOI: 10.3389/fendo.2024.1486793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 12/18/2024] [Indexed: 02/04/2025] Open
Abstract
Aims/hypothesis The gut microbiota play crucial roles in the digestion and degradation of nutrients, synthesis of biological agents, development of the immune system, and maintenance of gastrointestinal integrity. Gut dysbiosis is thought to be associated with type 2 diabetes mellitus (T2DM), one of the world's fastest growing diseases. The aim of this systematic review is to identify differences in the composition and diversity of the gut microbiota in individuals with T2DM. Methods A systematic search was conducted to identify studies reporting on the difference in gut microbiota composition between individuals with T2DM and healthy controls. Relevant studies were evaluated, and their characteristics and results were extracted using a standardized data extraction form. The studies were assessed for risk of bias and their findings were reported narratively. Results 58 observational studies published between 2010 and 2024 were included. Beta diversity was commonly reported to be different between individuals with T2DM and healthy individuals. Genera Lactobacillus, Escherichia-Shigella, Enterococcus, Subdoligranulum and Fusobacteria were found to be positively associated; while Akkermansia, Bifidobacterium, Bacteroides, Roseburia, Faecalibacteirum and Prevotella were found to be negatively associated with T2DM. Conclusions This systematic review demonstrates a strong association between T2DM and gut dysbiosis, as evidenced by differential microbial abundances and altered diversity indices. Among these taxa, Escherichia-Shigella is consistently associated with T2DM, whereas Faecalibacterium prausnitzii appears to offer a protective effect against T2DM. However, the heterogeneity and observational nature of these studies preclude the establishment of causative relationships. Future research should incorporate age, diet and medication-matched controls, and include functional analysis of these gut microbes. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42023459937.
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Affiliation(s)
- Serena Chong
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- South West Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Mike Lin
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Garvan Institute of Research, Sydney, NSW, Australia
| | - Deborah Chong
- Animal Health Laboratory, Department of Natural Resources and Environment Tasmania, Tasmania, TAS, Australia
| | - Slade Jensen
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- Infectious Disease and Microbiology, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- School of Medicine Antibiotic Resistance and Mobile Elements Groups, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
| | - Namson S. Lau
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- South West Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
- Liverpool Diabetes Collaboration, Ingham Institute of Applied Medical Research, Sydney, NSW, Australia
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32
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Wu XR, He XH, Xie YF. Characteristics of gut microbiota dysbiosis in patients with colorectal polyps. World J Gastrointest Oncol 2025; 17:98872. [PMID: 39817124 PMCID: PMC11664624 DOI: 10.4251/wjgo.v17.i1.98872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/05/2024] [Accepted: 09/19/2024] [Indexed: 12/12/2024] Open
Abstract
This editorial, inspired by a recent study published in the World Journal of Gastrointestinal Oncology, covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of Klebsiella, Parvimonas, and Clostridium increase, while those of Bifidobacterium and Lactobacillus decrease. This dysbiosis may promote the formation and recurrence of polyps. Similar microbial changes have also been observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome, indicating the role of increased pathogens and decreased probiotics in these conditions. Regulating the gut microbiota, particularly by increasing probiotic levels, may help prevent polyp recurrence and promote gut health. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.
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Affiliation(s)
- Xian-Rong Wu
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
| | - Xiao-Hong He
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
| | - Yong-Fang Xie
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
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Ito E, Ohki T, Toya N, Emoto T, Yamashita T, Sugiyama T, Yamada T, Mori H, Toyoda A, Hirata KI. Metagenomic Analysis of Gut Microbiota for Abdominal Aortic Aneurysm. Ann Vasc Dis 2025; 18:24-00105. [PMID: 39877321 PMCID: PMC11771153 DOI: 10.3400/avd.oa.24-00105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 12/02/2024] [Indexed: 01/31/2025] Open
Abstract
Objectives: The pathophysiological mechanism of abdominal aortic aneurysm (AAA) remains unclear. We previously reported that Bifidobacterium adolescentis levels were reduced in the feces of patients with AAA by 16S ribosomal ribonucleic acid (RNA) gene sequencing. In this study, we increased the number of cases and conducted metagenomic analyses to examine bacterial genes associated with the pathophysiology of AAA. Methods: For gut microbiota data, feces from 55 patients with AAA and 52 patients with no history of AAA, lower extremity artery disease, or coronary artery disease (control group) were collected. Metagenomic analysis was performed by collecting raw stool samples from patients. For intestinal microbiota analysis, metagenomic analysis of the fecal samples was performed. Results: Oral bacteria, including Actinomyces oris (p <0.0001), Streptococcus salivarius (p <0.001), Lactobacillus salivarius (p <0.001), and Streptococcus sp. (p <0.001), were increased in the feces of patients with AAA. In addition, bacterial genes related to alpha lipoic acid (ALA) biosynthesis (M00882, M00883, and M00884, p <0.0001) were decreased in patients with AAA. Conclusions: In the feces of patients with AAA, there was an increase in oral bacteria, and the expression of bacterial genes related to ALA biosynthesis was reduced. The results suggest the possibility of developing gut microbial drug treatments for AAA.
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Affiliation(s)
- Eisaku Ito
- Division of Vascular Surgery, The Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Takao Ohki
- Division of Vascular Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Naoki Toya
- Division of Vascular Surgery, The Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Takuo Emoto
- Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tomoya Yamashita
- Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tomomi Sugiyama
- School of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan
| | - Takuji Yamada
- School of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan
| | - Hiroshi Mori
- Advanced Genomics Center, National Institute of Genetics, Mishima, Sizuoka, Japan
| | - Atsushi Toyoda
- Advanced Genomics Center, National Institute of Genetics, Mishima, Sizuoka, Japan
| | - Ken-Ichi Hirata
- Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
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Leng X, Wei X, Wang J, Yao X, Zhang M, Sun D, Liang J, Chi L, Cheng Y. Impacts of intestinal microbiota metabolite trimethylamine N-oxide on cardiovascular disease: a bibliometric analysis. Front Microbiol 2025; 15:1491731. [PMID: 39834376 PMCID: PMC11743947 DOI: 10.3389/fmicb.2024.1491731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 12/16/2024] [Indexed: 01/22/2025] Open
Abstract
Background Trimethylamine N-oxide (TMAO), a metabolite dependent on intestinal microbiota, is closely related to the emergence, progression, and prognosis of cardiovascular disease (CVD), and has received increasing attention in recent years. Objective The current research hotspots and future development trends in TMAO and CVD field are found through bibliometrics analysis, which provides reference for further study. Methods The bibliometrics tools VOSviewer and CiteSpace were used to analyze the publications from the Web of Science Core Collection (WOSCC) database. The articles published from 2004 to 2024 about the relationship between TMAO and CVD were retrieved. Bibliometric analysis includes annual publications, countries/regions, institutions, authors and co-cited authors, journals and cited-journals, references and keywords. Results After searching and screening, 1,466 publications were included for subsequent bibliometric analysis. Since 2014, the number of publications exposing the relationship between TMAO and CVD has increased rapidly, as has the frequency of citations. China, USA and Italy are the countries that publish the most relevant research. Cleveland Clinic is the leading institution in this field. Stanley L Hazen, Zeneng Wang and W H Wilson Tang are the most prolific authors in this field, and the latter two have the closest academic cooperation. American Journal of Clinical Nutrition and Journal of the American Heart Association are influential journals that publish research in this field. "Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk" is the most frequently cited article. Keyword analysis shows that gut microbiota, metabolism, phosphatidylcholine and atherosclerosis (AS) are the hotspots in this field. Conclusion This study summarizes the research situation of TMAO and CVD in the past 20 years, focusing on the effect of TMAO on pathogenesis of AS, predictive value of TMAO on CVD risk, and dietary and drug intervention for TMAO. Probiotics and natural products may be the research focus of preventing and treating CVD by intervening TMAO in the future.
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Affiliation(s)
- Xiaohui Leng
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
- Yantai Yuhuangding Hospital, Yantai, China
| | - Xiunan Wei
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jun Wang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiaodong Yao
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Miaomiao Zhang
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Dajuan Sun
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Junwei Liang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lili Chi
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yan Cheng
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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35
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Jiang Y, Wang Y, Che L, Yang S, Zhang X, Lin Y, Shi Y, Zou N, Wang S, Zhang Y, Zhao Z, Li S. GutMetaNet: an integrated database for exploring horizontal gene transfer and functional redundancy in the human gut microbiome. Nucleic Acids Res 2025; 53:D772-D782. [PMID: 39526401 PMCID: PMC11701528 DOI: 10.1093/nar/gkae1007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 10/09/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024] Open
Abstract
Metagenomic studies have revealed the critical roles of complex microbial interactions, including horizontal gene transfer (HGT) and functional redundancy (FR), in shaping the gut microbiome's functional capacity and resilience. However, the lack of comprehensive data integration and systematic analysis approaches has limited the in-depth exploration of HGT and FR dynamics across large-scale gut microbiome datasets. To address this gap, we present GutMetaNet (https://gutmetanet.deepomics.org/), a first-of-its-kind database integrating extensive human gut microbiome data with comprehensive HGT and FR analyses. GutMetaNet contains 21 567 human gut metagenome samples with whole-genome shotgun sequencing data related to various health conditions. Through systematic analysis, we have characterized the taxonomic profiles and FR profiles, and identified 14 636 HGT events using a shared reference genome database across the collected samples. These HGT events have been curated into 8049 clusters, which are annotated with categorized mobile genetic elements, including transposons, prophages, integrative mobilizable elements, genomic islands, integrative conjugative elements and group II introns. Additionally, GutMetaNet incorporates automated analyses and visualizations for the HGT events and FR, serving as an efficient platform for in-depth exploration of the interactions among gut microbiome taxa and their implications for human health.
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Affiliation(s)
- Yiqi Jiang
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
| | - Yanfei Wang
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
| | - Lijia Che
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
| | - Shuo Yang
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
| | - Xianglilan Zhang
- State Key Laboratory of Pathogen and Biosafety, 20 East Street, Fengtai District, Beijing, 100071, China
| | - Yu Lin
- State Key Laboratory of Pathogen and Biosafety, 20 East Street, Fengtai District, Beijing, 100071, China
- Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, Beijing, 100029, China
| | - Yucheng Shi
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
| | - Nanhe Zou
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
| | - Shuai Wang
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
| | - Yuanzheng Zhang
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
| | - Zicheng Zhao
- OmicLab Limited, Unit 917, 19 Science Park West Avenue, New Territories, Hong Kong
| | - Shuai Cheng Li
- City University of Hong Kong Shenzhen Research Institute, 8 Yue Xing Yi Road, Nanshan District, Shenzhen, 518057, China
- Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong
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Zhao Y, Sun Y, Han Y, Li J, Ding N, Shibata T, Wu Q. Effect of micro-granular activated carbon on bacteriophage MS2 removal and fouling control in flat-plate MBR. ENVIRONMENTAL RESEARCH 2025; 264:120408. [PMID: 39577717 DOI: 10.1016/j.envres.2024.120408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/12/2024] [Accepted: 11/19/2024] [Indexed: 11/24/2024]
Abstract
Pathogenic microorganisms pose a severe risk to the aquatic environment and human health. Membrane bioreactors (MBRs) have attracted much attention due to their simultaneous biological treatment and virus retention, but membrane fouling is the main obstacle. This study explored the effect of micro-granular activated carbon (μGAC) on bacteriophage MS2 removal efficiency and membrane fouling in a flat-plate MBR. The results showed that the μGAC addition with a particle size of 180-300 μm improved the removal of MS2 (LRVMBR of 4.77 log) and enhanced the removal of COD and ammonia nitrogen. The μGAC integrated MBR (μGAC-MBR) exhibited a higher MS2 retention rate by the membrane filter layers with an average LVRMem of 2.03 log compared to that of a control reactor (C-MBR) of 1.89 log. Meanwhile, the total membrane filter layer resistance of μGAC-MBR was significantly lower than that of C-MBR, particularly in terms of cake layer resistance and organic pore-blocking exclusion. The μGAC addition slightly reduced MS2 adsorption by the activated sludge while significantly altering the extracellular polymeric substances (EPS) profiles. The fluorescent components in the bound EPS and PN/PS ratio of the activated sludge were reduced. We found that μGAC enhanced membrane surface roughness and hydrophilicity. Notably, the μGAC significantly influenced the quorum sensing (QS) systems, reducing the abundance and synthesis of AHL-related genes. The synthase luxI in the AHL-QS system was reduced by 93.21% in μGAC-MBR. The AHL-QS system is closely related to biofilm formation, and the total EPS of the surface filer layer of μGAC-MBR decreased by 57.73%, and PN in LB-EPS and TB-EPS decreased by 91.33% and 54.44% compared with C-MBR, indicating a significant reduction in biofilm formation. This study exhibited a new perspective on promoting MS2 removal with the synergistic effect of alleviating fouling in the MBR process.
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Affiliation(s)
- Yikan Zhao
- Department of Environmental Science and Engineering, State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, 100048, China
| | - Yingxue Sun
- Department of Environmental Science and Engineering, State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, 100048, China.
| | - Yuting Han
- Department of Environmental Science and Engineering, State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, 100048, China
| | - Jiahao Li
- Department of Environmental Science and Engineering, State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, 100048, China
| | - Ning Ding
- Department of Environmental Science and Engineering, State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, 100048, China.
| | - Toshiyuki Shibata
- Kubota Environmental Engineering (Shanghai) Co., Ltd., Shanghai, 200070, China
| | - Qianyuan Wu
- Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental Safety, Key Laboratory of Microorganism Application and Risk Control of Shenzhen, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China
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37
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Abdulrahim AO, Doddapaneni NSP, Salman N, Giridharan A, Thomas J, Sharma K, Abboud E, Rochill K, Shreelakshmi B, Gupta V, Lakkimsetti M, Mowo-Wale A, Ali N. The gut-heart axis: a review of gut microbiota, dysbiosis, and cardiovascular disease development. Ann Med Surg (Lond) 2025; 87:177-191. [PMID: 40109640 PMCID: PMC11918638 DOI: 10.1097/ms9.0000000000002789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 11/20/2024] [Indexed: 03/22/2025] Open
Abstract
Background Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality worldwide and there are strong links existing between gut health and cardiovascular health. Gut microbial diversity determines gut health. Dysbiosis, described as altered gut microbiota, causes bacterial translocations and abnormal gut byproducts resulting in systemic inflammation. Objective To review the current literature on the relationships between gut microbiota, dysbiosis, and CVD development, and explore therapeutic methods to prevent dysbiosis and support cardiovascular health. Summary Dysbiosis increases levels of pro-inflammatory substances while reducing those of anti-inflammatory substances. This accumulative inflammatory effect negatively modulates the immune system and promotes vascular dysfunction and atherosclerosis. High Firmicutes to Bacteroidetes ratios, high trimethylamine-n-oxide to short-chain fatty acid ratios, high indole sulfate levels, low cardiac output, and polypharmacy are all associated with worse cardiovascular outcomes. Supplementation with prebiotics and probiotics potentially alleviates some CVD risk. Blood and stool samples may be used in clinical practice to quantify and qualify gut bacterial ratios and byproducts, assess patients' risk for adverse cardiovascular outcomes, and track their gut health progress. Further research is required to set population-based cutoffs for normal and abnormal gut microbiota and byproduct ratios.
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Affiliation(s)
| | | | - Nadhra Salman
- Department of Internal Medicine, Baqai Medical University, Karachi, Pakistan
| | | | | | - Kavya Sharma
- Maharishi Markandeshwar Medical College and Hospital, Himachal Pradesh, India
| | - Elias Abboud
- Faculty of Medicine, University of Saint Joseph, Beirut, Lebanon
| | | | - B Shreelakshmi
- Navodaya Medical College Hospital & Research Centre, Karnataka, India
| | | | | | | | - Noor Ali
- Dubai Medical College, Dubai, United Arab Emirates
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Ren D, Liu S, Qin H, Huang M, Bai X, Han X, Zhang S, Mao J. Metagenomics-based insights into the microbial community dynamics and flavor development potentiality of artificial and natural pit mud. Food Microbiol 2025; 125:104646. [PMID: 39448156 DOI: 10.1016/j.fm.2024.104646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 08/25/2024] [Accepted: 09/23/2024] [Indexed: 10/26/2024]
Abstract
Strong-flavor Baijiu (SFB) production has relied on pit mud (PM) as a starter culture. The maturation time of natural PM (NPM) is about 30 years, so artificial PM (APM) with a shorter maturation time has attracted widespread attention. This study reveals the microbial and functional dissimilarities of APM and NPM, and helps to elucidate the different metabolic roles of microbes during substrate degradation and flavor formation. Significant differences in the microbial community were observed between APM and NPM, manifesting as variations in the abundance of core microorganisms. Total of 187 high-quality metagenome-assembled genomes (MAGs) were obtained based on the metagenomic binning technology, mainly including Firmicutes (n = 106), Bacteroidota (n = 15) and Chloroflexota (n = 14). Furthermore, the relative concentration of flavor compounds in 4-year APM was similar to those in 30-year NPM, but different from those in 100-year NPMs. Methanosarcina, Methanobacterium, Methanoculleus, Anaerolineae bacterium and Aminobacterium were the key bacteria responsible for the flavor differences. From a functional perspective, amino acid and carbohydrate metabolism were key functions of PM microbial, and showed differences between APM and NPM. Finally, substrate degradation and flavor generation pathways were found to exist in multiple microorganisms. Combine the relative abundance of microorganisms with the absolute abundance of enzymes, Clostridium, Lactobacillus, Petrimonas, Methanoculleus, Prevotella, Methanobacterium, Methanosarcina, Methanothrix, Proteiniphilum, Bellilinea, Anaerolinea, Anaeromassilibacillus, Syntrophomonas and Brevefilum were identified as the key microorganisms in APM and NPM.
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Affiliation(s)
- Dongliang Ren
- State Key Laboratory of Food Science and Resources, National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Shuangping Liu
- State Key Laboratory of Food Science and Resources, National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; Shaoxing Key Laboratory of Traditional Fermentation Food and Human Health, Jiangnan University (Shaoxing) Industrial Technology Research Institute, Shaoxing, 312000, China; National Engineering Research Center of Huangjiu, Zhejiang Guyuelongshan Shaoxing Wine CO., LTD, Shaoxing, 312000, Zhejiang, China.
| | - Hui Qin
- National Engineering Research Center of Solid-state Brewing. Luzhou Laojiao Group Co. Ltd, Luzhou, 646000, China
| | - Mengyang Huang
- National Engineering Research Center of Solid-state Brewing. Luzhou Laojiao Group Co. Ltd, Luzhou, 646000, China
| | - Xiaolin Bai
- State Key Laboratory of Food Science and Resources, National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Xiao Han
- State Key Laboratory of Food Science and Resources, National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; Shaoxing Key Laboratory of Traditional Fermentation Food and Human Health, Jiangnan University (Shaoxing) Industrial Technology Research Institute, Shaoxing, 312000, China; National Engineering Research Center of Huangjiu, Zhejiang Guyuelongshan Shaoxing Wine CO., LTD, Shaoxing, 312000, Zhejiang, China
| | - Suyi Zhang
- National Engineering Research Center of Solid-state Brewing. Luzhou Laojiao Group Co. Ltd, Luzhou, 646000, China.
| | - Jian Mao
- State Key Laboratory of Food Science and Resources, National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; Shaoxing Key Laboratory of Traditional Fermentation Food and Human Health, Jiangnan University (Shaoxing) Industrial Technology Research Institute, Shaoxing, 312000, China; National Engineering Research Center of Huangjiu, Zhejiang Guyuelongshan Shaoxing Wine CO., LTD, Shaoxing, 312000, Zhejiang, China.
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39
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Arioglu‐Tuncil S, Deemer D, Lindemann SR, Tunçil YE. Coconut ( Cocos nucifera L.) and Carob ( Ceratonia siliqua L.) Flours Dietary Fibers Differentially Impact Fecal Microbiota Composition and Metabolic Outputs In Vitro. Food Sci Nutr 2025; 13:e4724. [PMID: 39867837 PMCID: PMC11762452 DOI: 10.1002/fsn3.4724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 12/12/2024] [Accepted: 12/17/2024] [Indexed: 01/28/2025] Open
Abstract
Alternative flours can reveal beneficial health effects. The aim of this study was to evaluate and compare the effects of dietary fibers (DFs) of coconut and carob flours on colonic microbiota compositions and function. Coconut flour DFs were found to be dominated by mannose-containing polysaccharides by gas chromatography (GC)/MS and spectrophotometer, whereas glucose and uronic acid were the main monosaccharide moieties in carob flour DFs. In vitro fecal fermentation analysis revealed that coconut flour DFs result in the generation of microbial butyrate as much as inulin does, which is known to be a butyrogenic prebiotic, but at a slower rate. Supportingly, coconut flour DFs promoted butyrate-producing bacteria including Roseburia and Coprococcus, whereas carob flour DFs stimulated Prevotella-related OTUs. In addition, higher microbial diversity was achieved at the end of the fermentation of coconut flour DFs by the fecal microbiota. This study clearly shows that alternative flours have distinct functionalities in terms of colonic microbiota composition and function, and coconut flour could be used as an alternative flour for the development of functional food products targeting colonic health.
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Affiliation(s)
- Seda Arioglu‐Tuncil
- Nutrition and Dietetics Department, Nezahat Keleşoğlu Health Sciences FacultyNecmettin Erbakan UniversityKonyaTürkiye
| | - Dane Deemer
- Whistler Center for Carbohydrate Research, Department of Food SciencePurdue UniversityWest LafayetteIndianaUSA
| | - Stephen R. Lindemann
- Whistler Center for Carbohydrate Research, Department of Food SciencePurdue UniversityWest LafayetteIndianaUSA
- Department of Nutrition Science and Department of Biological SciencePurdue UniversityWest LafayetteIndianaUSA
| | - Yunus E. Tunçil
- Food Engineering Department, Engineering FacultyNecmettin Erbakan UniversityKonyaTürkiye
- Edical and Cosmetic Plants Application and Research CenterNecmettin Erbakan UniversityKonyaTürkiye
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40
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Salvado R, Lugones-Sánchez C, Santos-Minguez S, González-Sánchez S, Quesada JA, Benito R, Rodríguez-Sánchez E, Gómez-Marcos MA, Guimarães-Cunha P, Hernandez-Rivas JM, Mira A, García-Ortiz L. Sex Differences in Gut Microbiota and Their Relation to Arterial Stiffness (MIVAS Study). Nutrients 2024; 17:53. [PMID: 39796488 PMCID: PMC11723250 DOI: 10.3390/nu17010053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 12/18/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Recent research highlights the potential role of sex-specific variations in cardiovascular disease. The gut microbiome has been shown to differ between the sexes in patients with cardiovascular risk factors. OBJECTIVES The main objective of this study is to analyze the differences between women and men in the relationship between gut microbiota and measures of arterial stiffness. METHODS We conducted a cross-sectional study in Spain, selecting 180 subjects (122 women, 58 men) aged between 45 and 74. Subjects with arterial stiffness were identified by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV) above 12 mm/s, cardio-ankle vascular index (CAVI) above nine, or brachial-ankle pulse wave velocity (ba-PWV) above 17.5 m/s. All other cases were considered subjects without arterial stiffness. The composition of the gut microbiome in fecal samples was determined by 16S rRNA sequencing. RESULTS We found that women have a more diverse microbiome than men (Shannon, p < 0.05). There is also a significant difference in gut microbiota composition between sexes (Bray-Curtis, p < 0.01). Dorea, Roseburia, and Agathobacter, all of them short-chain fatty-acid producers, were more abundant in women's microbiota (log values > 1, p-value and FDR < 0.05). Additionally, Blautia was more abundant in women when only the subjects with arterial stiffness were considered. According to logistic regression, Roseburia was negatively associated with arterial stiffness in men, while Bifidobacterium and Subdoligranulum were positively related to arterial stiffness. CONCLUSIONS In the Spanish population under study, women had higher microbiome diversity and potentially protective genera. The host's gender determines the influence of the same bacteria on arterial stiffness. TRIAL REGISTRATION NUMBER NCT03900338.
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Affiliation(s)
- Rita Salvado
- Primary Care Research Unit of Salamanca (APISAL), Salamanca Primary Healthcare Management, Castilla y León Regional Health Authority (SACyL), Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain; (C.L.-S.); (S.G.-S.); (M.A.G.-M.); (L.G.-O.)
| | - Cristina Lugones-Sánchez
- Primary Care Research Unit of Salamanca (APISAL), Salamanca Primary Healthcare Management, Castilla y León Regional Health Authority (SACyL), Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain; (C.L.-S.); (S.G.-S.); (M.A.G.-M.); (L.G.-O.)
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), 37005 Salamanca, Spain
| | - Sandra Santos-Minguez
- Cancer Research Centre, Institute of Molecular and Cellular Biology of Cancer (IBMCC), Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca—CSIC, 37007 Salamanca, Spain; (S.S.-M.); (J.M.H.-R.)
| | - Susana González-Sánchez
- Primary Care Research Unit of Salamanca (APISAL), Salamanca Primary Healthcare Management, Castilla y León Regional Health Authority (SACyL), Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain; (C.L.-S.); (S.G.-S.); (M.A.G.-M.); (L.G.-O.)
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), 37005 Salamanca, Spain
| | - José A. Quesada
- Clinical Medicine Department, Miguel Hernandez University, 03550 Alicante, Spain;
- Network of Research on Chronicity, Primary Care and Health Promotion (RICAPPS), 03550 Alicante, Spain
| | - Rocío Benito
- Cancer Research Centre, Institute of Molecular and Cellular Biology of Cancer (IBMCC), Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca—CSIC, 37007 Salamanca, Spain; (S.S.-M.); (J.M.H.-R.)
| | - Emiliano Rodríguez-Sánchez
- Primary Care Research Unit of Salamanca (APISAL), Salamanca Primary Healthcare Management, Castilla y León Regional Health Authority (SACyL), Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain; (C.L.-S.); (S.G.-S.); (M.A.G.-M.); (L.G.-O.)
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), 37005 Salamanca, Spain
- Department of Medicine, University of Salamanca (USAL), 37007 Salamanca, Spain
| | - Manuel A. Gómez-Marcos
- Primary Care Research Unit of Salamanca (APISAL), Salamanca Primary Healthcare Management, Castilla y León Regional Health Authority (SACyL), Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain; (C.L.-S.); (S.G.-S.); (M.A.G.-M.); (L.G.-O.)
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), 37005 Salamanca, Spain
- Department of Medicine, University of Salamanca (USAL), 37007 Salamanca, Spain
| | - Pedro Guimarães-Cunha
- Unidade Local de Saúde do Alto Ave, Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, 4835-044 Guimarâes, Portugal
- Life and Health Sciences Research Institute (IICVS), School of Medicine, Minho University, 4704-553 Braga, Portugal
| | - Jesús M. Hernandez-Rivas
- Cancer Research Centre, Institute of Molecular and Cellular Biology of Cancer (IBMCC), Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca—CSIC, 37007 Salamanca, Spain; (S.S.-M.); (J.M.H.-R.)
- Department of Medicine, University of Salamanca (USAL), 37007 Salamanca, Spain
- Haematology Department, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca (USAL), 37007 Salamanca, Spain
| | - Alex Mira
- Department of Health and Genomics, FISABIO Foundation, 46020 Valencia, Spain;
- CIBER Center for Epidemiology and Public Health, 28029 Madrid, Spain
| | - Luis García-Ortiz
- Primary Care Research Unit of Salamanca (APISAL), Salamanca Primary Healthcare Management, Castilla y León Regional Health Authority (SACyL), Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain; (C.L.-S.); (S.G.-S.); (M.A.G.-M.); (L.G.-O.)
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), 37005 Salamanca, Spain
- Department of Biomedical and Diagnostic Sciences, University of Salamanca, 37007 Salamanca, Spain
| | - MIVAS Investigators
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), 37005 Salamanca, Spain
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Sagmeister A, Matter CM, Stähli BE, Scharl M. The Gut-Heart Axis: Effects of Intestinal Microbiome Modulation on Cardiovascular Disease-Ready for Therapeutic Interventions? Int J Mol Sci 2024; 25:13529. [PMID: 39769292 PMCID: PMC11676197 DOI: 10.3390/ijms252413529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/10/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025] Open
Abstract
Recent reports demonstrate an association between distinct bacteria or bacteria-derived metabolites originating from the gut microbiome and the onset or progression of cardiovascular disease (CVD). This raises the opportunity to modulate the gut microbiome to prevent or treat CVD. To investigate whether intestinal microbiome modulation can prevent or treat CVD, this systematic literature review includes all randomized clinical trials on microbiome modulation and its effects on CVD risk published between August 2018 and August 2023. Within this review, we report the modulation of the gut microbiome by a variety of interventions and their effects on CVD, focusing on cardiovascular risk factors and risk markers of CVD. Beneficial effects were observed upon lifestyle intervention and probiotics use. The most promising diets for reducing risk factors of CVD were the Mediterranean diet, high-fiber diets, polyphenol-rich diets, and diets containing polyunsaturated fatty acids. Among drug interventions, only empagliflozin showed beneficial effects on CVD risk factors. Many dietary interventions were less conclusive because of the heterogeneity of study populations, small sample sizes, and short intervention windows or follow-up. Diet, lifestyle, probiotics, or drug interventions can modulate the gut microbiome and decrease risk markers or risk factors related to CVD. Yet, their effects on clinical endpoints remain to be determined.
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Affiliation(s)
- Alexandra Sagmeister
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland;
| | - Christian M. Matter
- Department of Cardiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (C.M.M.); (B.E.S.)
| | - Barbara E. Stähli
- Department of Cardiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (C.M.M.); (B.E.S.)
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland;
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Raghani N, Postwala H, Shah Y, Chorawala M, Parekh P. From Gut to Brain: Unraveling the Intricate Link Between Microbiome and Stroke. Probiotics Antimicrob Proteins 2024; 16:2039-2053. [PMID: 38831225 DOI: 10.1007/s12602-024-10295-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/16/2024] [Indexed: 06/05/2024]
Abstract
Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively.
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Affiliation(s)
- Neha Raghani
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, 380009, Gujarat, India
| | - Humzah Postwala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, 380009, Gujarat, India
| | - Yesha Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, 380009, Gujarat, India
| | - Mehul Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, 380009, Gujarat, India.
| | - Priyajeet Parekh
- AV Pharma LLC, 1545 University Blvd N Ste A, Jacksonville, FL, 32211, USA
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Zhang Y, Wang H, Sang Y, Liu M, Wang Q, Yang H, Li X. Gut microbiota in health and disease: advances and future prospects. MedComm (Beijing) 2024; 5:e70012. [PMID: 39568773 PMCID: PMC11577303 DOI: 10.1002/mco2.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 10/02/2024] [Accepted: 10/10/2024] [Indexed: 11/22/2024] Open
Abstract
The gut microbiota plays a critical role in maintaining human health, influencing a wide range of physiological processes, including immune regulation, metabolism, and neurological function. Recent studies have shown that imbalances in gut microbiota composition can contribute to the onset and progression of various diseases, such as metabolic disorders (e.g., obesity and diabetes) and neurodegenerative conditions (e.g., Alzheimer's and Parkinson's). These conditions are often accompanied by chronic inflammation and dysregulated immune responses, which are closely linked to specific forms of cell death, including pyroptosis and ferroptosis. Pathogenic bacteria in the gut can trigger these cell death pathways through toxin release, while probiotics have been found to mitigate these effects by modulating immune responses. Despite these insights, the precise mechanisms through which the gut microbiota influences these diseases remain insufficiently understood. This review consolidates recent findings on the impact of gut microbiota in these immune-mediated and inflammation-associated conditions. It also identifies gaps in current research and explores the potential of advanced technologies, such as organ-on-chip models and the microbiome-gut-organ axis, for deepening our understanding. Emerging tools, including single-bacterium omics and spatial metabolomics, are discussed for their promise in elucidating the microbiota's role in disease development.
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Affiliation(s)
- Yusheng Zhang
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research Center China Academy of Chinese Medical Sciences Beijing China
| | - Hong Wang
- School of Traditional Chinese Medicine Southern Medical University Guangzhou China
| | - Yiwei Sang
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research Center China Academy of Chinese Medical Sciences Beijing China
| | - Mei Liu
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research Center China Academy of Chinese Medical Sciences Beijing China
| | - Qing Wang
- School of Life Sciences Beijing University of Chinese Medicine Beijing China
| | - Hongjun Yang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs China Academy of Chinese Medical Sciences Beijing China
| | - Xianyu Li
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research Center China Academy of Chinese Medical Sciences Beijing China
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Wang T, Luo Y, Kong X, Fang L, Zhu L, Yu B, Zheng P, Huang Z, Mao X, Jie Y, Luo J, Yan H, He J. Multiomics comparative analysis of feces AMRGs of Duroc pigs and Tibetan and the effect of fecal microbiota transplantation on AMRGs upon antibiotic exposure. Microbiol Spectr 2024; 13:e0198324. [PMID: 39612216 PMCID: PMC12054024 DOI: 10.1128/spectrum.01983-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 11/12/2024] [Indexed: 11/30/2024] Open
Abstract
Fecal matter is recognized as both a reservoir and a transmission source for various antimicrobial resistance genes (AMRGs). However, the transcriptional activity of AMRGs in swine feces is not well understood. In addition, the effect of fecal microbiota transplantation (FMT) on the excretion of AMRGs has rarely been reported. Our study explored the diversity, abundance, transcriptional activity, and bacterial hosts of AMRGs in Tibetan and Duroc pig feces using metagenomic and metatranscriptomic sequencing technologies. We discovered a significantly higher genomic abundance of AMRGs in the feces of Duroc pigs compared to Tibetan pigs (P < 0.001), although the transcript levels did not show a significant difference. The results showed that the core composition of AMRGs in pig feces varied considerably, with the most transcriptionally active AMRGs being oqxB, tetQ, Bla1, dfrA1, and amrB. Furthermore, the Firmicutes phylum is the main host of AMRGs. By transplanting fecal flora from Tibetan and Duroc pigs into the intestines of Duroc Landrace Yorkshire (DLY) piglets after acute antibiotic exposure, we found that only Tibetan pig fecal flora significantly reduced AMRGs in the feces of DLY piglets (P < 0.05). The effectiveness of Tibetan pig fecal microorganisms in removing AMRGs from DLY pig feces was mainly influenced by microbial communities, especially the Bacteroidota phylum. These findings offer valuable insights for the prevention and control of AMRG pollution. IMPORTANCE To the best of our knowledge, this study represents the first comprehensive analysis of antimicrobial resistance gene (AMRGs) expression in the fecal microbiota of Tibetan and Duroc pigs, employing an integrated metagenomic and metatranscriptomic approach. Our findings indicate a higher risk of AMRGs transmission in the feces of Duroc pigs compared to Tibetan pigs. Given the escalating antimicrobial resistance crisis, novel therapeutic interventions are imperative to mitigate gut colonization by pathogens and AMRGs. In this regard, we investigated the impact of fecal microbiota from Tibetan and Duroc pig sources on AMRGs excretion in Duroc Landrace Yorkshire (DLY) piglets' feces following acute antibiotic exposure. Remarkably, only fecal microbiota sourced from Tibetan pigs exhibited a reduction in AMRGs excretion in DLY piglets' feces. This underscores the significance of evaluating the presence of AMRGs within donor fecal microbiota for effective AMRGs decolonization strategies.
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Affiliation(s)
- Tao Wang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Yuheng Luo
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Xiangfeng Kong
- Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China
| | - Ling Fang
- Zhucheng Haotian Pharmaceutical Co., Ltd, Zhucheng, Shandong, China
| | - Liping Zhu
- Zhucheng Haotian Pharmaceutical Co., Ltd, Zhucheng, Shandong, China
| | - Bing Yu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Ping Zheng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Zhiqing Huang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Xiangbing Mao
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Yu Jie
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Junqiu Luo
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Hui Yan
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
| | - Jun He
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
- Key Laboratory of Animal Disease-resistant Nutrition, Chengdu, Sichuan, China
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Miao Y, Xie L, Chen S, Zhang X, Liu W, Xie P. Ketogenic diet in treating sepsis-related acquired weakness: is it friend or foe? Front Nutr 2024; 11:1484856. [PMID: 39668897 PMCID: PMC11636000 DOI: 10.3389/fnut.2024.1484856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 11/05/2024] [Indexed: 12/14/2024] Open
Abstract
Background Sepsis is the body's extreme response to an infection leading to organ dysfunction. Sepsis-related acquired weakness (SAW), a critical illness closely related to metabolic disorders, is characterized by generalized sepsis-induced skeletal muscle weakness, mainly manifesting as symmetrical atrophy of respiratory and limb muscles. Muscle accounts for 40% of the body's total mass and is one of the major sites of glucose and energy absorption. Diet affects skeletal muscle metabolism, which further impacts physiology and signaling pathways. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has shown benefits in patients with a variety of neuromuscular disorders. Patients with SAW are in a hypermetabolic state and can consume approximately 1% of total body muscle mass in a day. Due to the decreased total body energy expenditure secondary to starvation, skeletal muscles enter a low metabolic state, with reduced gluconeogenesis and protein consumption and elevated levels of ketone bodies. The latest research suggests that KD may be a new strategy for SAW prevention and treatment, but its mechanism is still unclear. Objective Our article aims to explore the effect and mechanism of KD on SAW. And we hope that our review will inspire further research on the KD and foster the exploration of novel strategies for combating SAW. Methods Search medical databases and related academic websites, using keywords such as "Sepsis-related acquired weakness," "ketogenic diet," and "skeletal muscle," and select representative literature. Using the method of induction and summary, analyze the effect and mechanism of KD on SAW. Results Compared with early nutrition, KD has a more protective effect on SAW, but its mechanism is complex. Firstly, KD can alter energy metabolism substrates to affect SAW's energy metabolism; Secondly, KD can directly act as a signaling molecule to improve mitochondrial function in skeletal muscle and stimulate skeletal muscle regeneration signaling molecules; Thirdly, KD can affect the gut microbiota to exert anti-inflammatory effects, enhance immunity, and thus protect SAW. Conclusion KD has a protective effect on SAW, which includes improving energy metabolism, stimulating muscle regeneration signals, optimizing gut microbiota composition, and reducing inflammation and oxidative stress.
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Affiliation(s)
- Yanmei Miao
- Department of Critical Care Medicine of the Third Affiliated Hospital (The First People's Hospital of Zunyi), Zunyi Medical University, Zunyi, China
| | - Leiyu Xie
- Department of Critical Care Medicine of the Third Affiliated Hospital (The First People's Hospital of Zunyi), Zunyi Medical University, Zunyi, China
| | - Shaolin Chen
- Department of Nursing of Affiliated Hospital, Zunyi Medical University, Zunyi, China
| | - Xiaoming Zhang
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
| | - Wenjie Liu
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Peng Xie
- Department of Critical Care Medicine of the Third Affiliated Hospital (The First People's Hospital of Zunyi), Zunyi Medical University, Zunyi, China
- Department of Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
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Młynarska E, Wasiak J, Gajewska A, Bilińska A, Steć G, Jasińska J, Rysz J, Franczyk B. Gut Microbiota and Gut-Brain Axis in Hypertension: Implications for Kidney and Cardiovascular Health-A Narrative Review. Nutrients 2024; 16:4079. [PMID: 39683474 DOI: 10.3390/nu16234079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 11/12/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
INTRODUCTION Arterial hypertension is a major contributor to a wide range of health complications, with cardiac hypertrophy and chronic kidney disease being among the most prevalent. Consequently, novel strategies for the treatment and prevention of hypertension are actively being explored. Recent research has highlighted a potential link between hypertension and the gut-brain axis. A bidirectional communication between the microbiota and the brain via the vagus nerve, enteric nervous system, hypothalamus-pituitary-adrenal axis, secreted short-chain fatty acids, and neurotransmitter metabolism. MATERIALS AND METHODS A comprehensive literature search was conducted using databases such as PubMed to identify studies exploring the relationship between gut microbiota and hypertension, along with the effects of dietary interventions and probiotics on blood pressure regulation. DISCUSSION Studies in both animal models and human subjects have demonstrated a strong correlation between alterations in gut microbiota composition and the development of hypertension. By influencing blood pressure, the gut microbiota can potentially affect the progression of cardiovascular and kidney disorders. Modulating gut microbiota through dietary interventions and probiotics has shown promise in regulating blood pressure and reducing systemic inflammation, offering a novel approach to managing hypertension. Diets such as the Mediterranean diet, which is rich in polyphenols and omega-3 fatty acids and low in sodium, promote the growth of beneficial gut bacteria that support cardiovascular health. Additionally, probiotics have been found to enhance gut barrier function, reduce inflammation, and modulate the Renin-Angiotensin System, all of which contribute to lowering blood pressure. CONCLUSIONS Further research is needed to determine the mechanisms of action of the microbiota in hypertension. The aim of this study was to evaluate the influence of gut microbiota on blood pressure regulation and the progression of hypertension-related complications, such as cardiovascular and kidney disorders.
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Affiliation(s)
- Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jakub Wasiak
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Agata Gajewska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Aleksandra Bilińska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Greta Steć
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Jasińska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
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Protasiewicz-Timofticiuc DC, Bădescu D, Moța M, Ștefan AG, Mitrea A, Clenciu D, Efrem IC, Roșu MM, Vladu BE, Gheonea TC, Moța E, Vladu IM. Back to Roots: Dysbiosis, Obesity, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Obstructive Sleep Apnea-Is There an Objective Connection? A Narrative Review. Nutrients 2024; 16:4057. [PMID: 39683451 DOI: 10.3390/nu16234057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 11/25/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
In recent decades, it has become clear that the gut is more than just a digestive organ; it also functions as an immune organ with regulatory capabilities and acts as a "second brain" that influences brain function due to the presence and regulatory roles of the gut microbiota (GM). The GM is a crucial component of its host and significantly impacts human health. Dysbiosis, or microbial imbalance, has been closely linked to various diseases, including gastrointestinal, neurological, psychiatric, and metabolic disorders. The aim of this narrative review is to highlight the roles of the GM in maintaining metabolic health. Sleep is a vital biological necessity, with living organisms having evolved an internal sleep-wake rhythm that aligns with a roughly 24 h light/dark cycle, and this is known as the circadian rhythm. This cycle is essential for tissue repair, restoration, and overall optimal body functioning. Sleep irregularities have become more prevalent in modern society, with fast-paced lifestyles often disrupting normal sleep patterns. Urban living factors, such as fast food consumption, shift work, exposure to artificial light and nighttime noise, medications, and social activities, can adversely affect circadian rhythms, with dysbiosis being one of the many factors incriminated in the etiology of sleep disorders.
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Affiliation(s)
| | - Diana Bădescu
- Department of Diabetes, Nutrition and Metabolic Diseases, County Clinical Emergency Hospital of Craiova, 200642 Craiova, Romania
| | - Maria Moța
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | | | - Adina Mitrea
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Diana Clenciu
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ion Cristian Efrem
- Department of Medical Semiology, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Maria Magdalena Roșu
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Midwives and Nursing, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Beatrice Elena Vladu
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Theodora Claudia Gheonea
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Eugen Moța
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ionela Mihaela Vladu
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Wu J, Li M, Zhou C, Rong J, Zhang F, Wen Y, Qu J, Wu R, Miao Y, Niu J. Changes in amino acid concentrations and the gut microbiota composition are implicated in the mucosal healing of ulcerative colitis and can be used as noninvasive diagnostic biomarkers. Clin Proteomics 2024; 21:62. [PMID: 39574001 PMCID: PMC11580342 DOI: 10.1186/s12014-024-09513-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 11/13/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Mucosal healing is the therapeutic target for ulcerative colitis (UC). While amino acids (AAs) and the gut microbiota are known to be involved in the pathogenesis of UC, their specific roles in mucosal healing have not been fully defined. OBJECTIVES To longitudinally assess the changes in AA concentrations and the gut microbiota composition in the context of mucosal healing in UC patients, with the aim of identifying new biomarkers with predictive value for mucosal healing in UC patients and providing a new theoretical basis for dietary therapy. METHODS A total of 15 UC patients with infliximab-induced mucosal healing were enrolled. Serum and fecal AA concentrations before and after mucosal healing were determined via targeted metabolomics. A receiver operating characteristic (ROC) curve was plotted to evaluate the value of different AAs in predicting mucosal healing in UC patients. The changes in the composition of the fecal gut microbiota were analyzed via metagenomics, and bioinformatics was used to analyze the functional genes and metabolic pathways associated with different bacterial species. Spearman correlation analyses of fecal AAs with significantly different concentrations and the differentially abundant bacterial species before and after mucosal healing were performed. RESULTS 1. The fecal concentrations of alanine, aspartic acid, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine were significantly decreased after mucosal healing. The serum concentrations of alanine, cysteine and valine significantly increased, whereas that of aspartic acid significantly decreased. Glutamic acid, leucine, lysine, methionine and threonine could accurately predict mucosal healing in UC patients, and the area under the curve (AUC) was > 0.9. After combining the 5 amino acids, the AUC reached 0.96. 2. There were significant differences in the gut microbiota composition before and after mucosal healing in UC, characterized by an increase in the abundance of beneficial microbiota (Faecalibacterium prausnitzii and Bacteroides fragilis) and a decrease in the abundance of harmful microbiota (Enterococcus faecalis). LEfSe analysis identified 57 species that could predict mucosal healing, and the AUC was 0.7846. 3. Amino acid metabolic pathways were enriched in samples after mucosal healing, was associated with the abundance of multiple species, such as Faecalibacterium prausnitzi, Bacteroides fragilis, Bacteroides vulgatus and Alistipes putredinis. 4. The fecal concentrations of several AAs were negatively correlated with the abundance of a variety of beneficial strains, such as Bacteroides fragilis, uncultured Clostridium sp., Firmicutes bacterium CAG:103, Adlercreutzia equolifaciens, Coprococcus comes and positively correlated with the abundance of several harmful strains, such as Citrobacter freundii, Enterococcus faecalis, Klebsiella aerogenes, Salmonella enterica. CONCLUSION Altered concentrations of amino acids and their associations with the gut microbiota are implicated in the mucosal healing of UC patients and can serve as noninvasive diagnostic biomarkers.
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Affiliation(s)
- Jing Wu
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Maojuan Li
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Chan Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Jiamei Rong
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Fengrui Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Yunling Wen
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Jinghong Qu
- Kunming Medical University, Kunming, Yunnan, China
| | - Rui Wu
- Kunming Medical University, Kunming, Yunnan, China
| | - Yinglei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China.
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China.
| | - Junkun Niu
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, China.
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China.
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Senaprom S, Namjud N, Ondee T, Bumrungpert A, Pongpirul K. Sugar Composition of Thai Desserts and Their Impact on the Gut Microbiome in Healthy Volunteers: A Randomized Controlled Trial. Nutrients 2024; 16:3933. [PMID: 39599719 PMCID: PMC11597037 DOI: 10.3390/nu16223933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 11/03/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The relationship between consuming Thai desserts-predominantly composed of carbohydrates-and gut microbiome profiles remains unclear. This study aimed to evaluate the effects of consuming various Thai desserts with different GI values on the gut microbiomes of healthy volunteers. METHODS This open-label, parallel randomized clinical trial involved 30 healthy individuals aged 18 to 45 years. Participants were randomly assigned to one of three groups: Phetchaburi's Custard Cake (192 g, low-GI group, n = 10), Saraburi's Curry Puff (98 g, medium-GI group, n = 10), and Lampang's Crispy Rice Cracker (68 g, high-GI group, n = 10), each consumed alongside their standard breakfast. Fecal samples were collected at baseline and 24 h post-intervention for metagenomic analysis of gut microbiome profiles using 16S rRNA gene sequencing. RESULTS After 24 h, distinct trends in the relative abundance of various gut microbiota were observed among the dessert groups. In the high-GI dessert group, the abundance of Collinsella and Bifidobacterium decreased compared to the low- and medium-GI groups, while Roseburia and Ruminococcus showed slight increases. Correlation analysis revealed a significant negative relationship between sugar intake and Lactobacillus abundance in the medium- and high-GI groups, but not in the low-GI group. Additionally, a moderately negative association was observed between Akkermansia abundance and sugar intake in the high-GI group. These bacteria are implicated in energy metabolism and insulin regulation. LEfSe analysis identified Porphyromonadaceae and Porphyromonas as core microbiota in the low-GI group, whereas Klebsiella was enriched in the high-GI group, with no predominant bacteria identified in the medium-GI group. CONCLUSIONS The findings suggest that Thai desserts with varying GI levels can influence specific gut bacteria, though these effects may be temporary.
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Affiliation(s)
- Sayamon Senaprom
- Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (S.S.); (N.N.); (T.O.)
| | - Nuttaphat Namjud
- Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (S.S.); (N.N.); (T.O.)
| | - Thunnicha Ondee
- Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (S.S.); (N.N.); (T.O.)
- Center of Excellence in Preventive and Integrative Medicine (CE-PIM), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Akkarach Bumrungpert
- College of Integrative Medicine, Dhurakij Pundit University, Bangkok 10210, Thailand;
| | - Krit Pongpirul
- Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (S.S.); (N.N.); (T.O.)
- Center of Excellence in Preventive and Integrative Medicine (CE-PIM), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Bumrungrad International Hospital, Bangkok 10110, Thailand
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
- Department of Infection Biology & Microbiomes, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 3GB, UK
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Lee JY, Bays DJ, Savage HP, Bäumler AJ. The human gut microbiome in health and disease: time for a new chapter? Infect Immun 2024; 92:e0030224. [PMID: 39347570 PMCID: PMC11556149 DOI: 10.1128/iai.00302-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/01/2024] Open
Abstract
The gut microbiome, composed of the colonic microbiota and their host environment, is important for many aspects of human health. A gut microbiome imbalance (gut dysbiosis) is associated with major causes of human morbidity and mortality. Despite the central part our gut microbiome plays in health and disease, mechanisms that maintain homeostasis and properties that demarcate dysbiosis remain largely undefined. Here we discuss that sorting taxa into meaningful ecological units reveals that the availability of respiratory electron acceptors, such as oxygen, in the host environment has a dominant influence on gut microbiome health. During homeostasis, host functions that limit the diffusion of oxygen into the colonic lumen shelter a microbial community dominated by primary fermenters from atmospheric oxygen. In turn, primary fermenters break down unabsorbed nutrients into fermentation products that support host nutrition. This symbiotic relationship is disrupted when host functions that limit the luminal availability of host-derived electron acceptors become weakened. The resulting changes in the host environment drive alterations in the microbiota composition, which feature an elevated abundance of facultatively anaerobic microbes. Thus, the part of the gut microbiome that becomes imbalanced during dysbiosis is the host environment, whereas changes in the microbiota composition are secondary to this underlying cause. This shift in our understanding of dysbiosis provides a novel starting point for therapeutic strategies to restore microbiome health. Such strategies can either target the microbes through metabolism-based editing or strengthen the host functions that control their environment.
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Affiliation(s)
- Jee-Yon Lee
- Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA
| | - Derek J. Bays
- Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of California Davis, Sacramento, California, USA
| | - Hannah P. Savage
- Department of Pathology Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, USA
| | - Andreas J. Bäumler
- Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA
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