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Petersen C, Satheesh Babu AK, Della Lucia CM, Paz HA, Iglesias-Carres L, Zhong Y, Jalili T, Symons JD, Shankar K, Neilson AP, Wankhade UD, Anandh Babu PV. Gut microbes metabolize strawberry phytochemicals and mediate their beneficial effects on vascular inflammation. Gut Microbes 2025; 17:2446375. [PMID: 39760464 DOI: 10.1080/19490976.2024.2446375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 11/02/2024] [Accepted: 12/18/2024] [Indexed: 01/07/2025] Open
Abstract
Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited. We addressed this knowledge gap using strawberry phytochemicals as a model. C57BL/6J mice were fed a standard diet [C]; strawberry-supplemented diet (~2 human servings) [CS]; strawberry-supplemented diet and treated with antibiotics (to deplete gut microbes) [CSA]; high-fat diet (HFD) [HF]; strawberry-supplemented HFD [HS]; and strawberry-supplemented HFD and treated with antibiotics [HSA] for 12 weeks. First, antibiotic treatment suppressed the production of selected metabolites (CSA vs. CS), and p-coumaric acid was identified as a strawberry-derived microbial metabolite. Second, HFD-induced dysbiosis negatively affected metabolite production (HS vs. HF), and hippuric acid was identified as a microbial metabolite in HFD conditions. Third, dietary strawberries improved HFD-induced vascular inflammation (HS vs. HF). However, antibiotic treatment reduced metabolite production and abolished the vascular effects of strawberries (HSA vs. HS), indicating the importance of gut microbes in mediating the vascular benefits of strawberries via metabolites. Fourth, strawberry supplementation decreased Coprobacillus that was positively associated with vascular inflammation, whereas it increased Lachnospiraceae that was negatively associated with vascular inflammation and positively associated with hippuric acid. Fifth, hippuric acid was negatively associated with vascular inflammation. Our study fills in some pieces of the giant puzzle regarding the influence of gut microbes on the biological activities of phytochemicals. HFD-induced gut dysbiosis negatively impacts metabolite production and a strong association exists among gut microbes, strawberry-derived microbial metabolites, and the vascular benefits of dietary strawberries. Further, our study provides significant proof of concept to warrant future research on the use of strawberries as a nutritional strategy to prevent vascular complications.
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Affiliation(s)
- Chrissa Petersen
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | | | - Ceres Mattos Della Lucia
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | - Henry A Paz
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Lisard Iglesias-Carres
- Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC, USA
| | - Ying Zhong
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Thunder Jalili
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | - J David Symons
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | - Kartik Shankar
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Andrew P Neilson
- Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC, USA
| | - Umesh D Wankhade
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Pon Velayutham Anandh Babu
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
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Jiang GH, Li HY, Xie LJ, Fan JY, Li SY, Yu WQ, Xu YT, He ML, Jiang Y, Bai X, Zhou J, Wang X. Intestinal flora was associated with occurrence risk of chronic non-communicable diseases. World J Gastroenterol 2025; 31:103507. [PMID: 40124279 PMCID: PMC11924013 DOI: 10.3748/wjg.v31.i11.103507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/26/2024] [Accepted: 02/24/2025] [Indexed: 03/13/2025] Open
Abstract
BACKGROUND The intestinal flora (IF) has been linked to risks of non-communicable diseases, especially various cancers, stroke, and Alzheimer's disease. However, many uncertainties of these associations during different stages of growth, development, and aging still exist. Therefore, further in-depth explorations are warranted. AIM To explore the associations of the human IF with disease risks during different stages of growth, development, and aging to achieve more accurate and convincing conclusions. METHODS Cohort, cross-sectional, case-control, and Mendelian randomization studies published in the PubMed and Web of Science databases until December 31, 2023 were systematically reviewed to clarify the associations of the IF at the genus level with the risks of various non-communicable diseases, which were grouped in accordance with the 10th revision of the International Classification of Diseases. RESULTS In total, 57 studies were included to quantitatively examine the influence of the IF on the risks of 30 non-communicable diseases during different stages of growth, development, and aging. Population studies and Mendelian randomization studies confirmed positive associations of the abundances of Bifidobacterium and Ruminococcus with multiple sclerosis. CONCLUSION These findings contribute to a deeper understanding of the roles of the IF and provide novel evidence for effective strategies for the prevention and treatment of non-communicable diseases. In the future, it will be necessary to explore a greater variety of research techniques to uncover the specific mechanisms by which gut microbiota trigger diseases and conduct in-depth studies on the temporal relationship between microbiota alterations and diseases, so as to clarify the causal relationship more accurately.
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Affiliation(s)
- Guo-Heng Jiang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong-Yu Li
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lin-Jun Xie
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jing-Yuan Fan
- China Tobacco Sichuan Industry Co. Ltd., Technology Center, Chengdu 610101, Sichuan Province, China
| | - Shi-Yi Li
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Qian Yu
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yi-Ting Xu
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Meng-Lin He
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yi Jiang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xuan Bai
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jin Zhou
- Department of Anorectal Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Xin Wang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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3
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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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Tashkent Y, Choo JM, Richard A, Wang Z, Calzadilla‐Bertot L, Vasil E, Miller S, Taylor SL, Ivey KL, Woodman R, Adler B, Ayonrinde OT, Olynyk JK, Beilin LJ, Mori TA, Wigg AJ, Muller KR, Adams LA, Rogers GB. Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology. Liver Int 2025; 45:e70032. [PMID: 39999013 PMCID: PMC11855901 DOI: 10.1111/liv.70032] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/28/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND AND AIMS Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults. METHODS AND RESULTS At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05). CONCLUSIONS SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction. TRIAL REGISTRATION The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).
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Affiliation(s)
- Yasmina Tashkent
- Microbiome and Host Health ProgramSouth Australian Health and Medical Research InstituteAdelaideSouth AustraliaAustralia
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
- South Australian Hepatology and Transplant Medicine UnitSouthern Adelaide Local Health NetworkBedford ParkSouth AustraliaAustralia
| | - Jocelyn M. Choo
- Microbiome and Host Health ProgramSouth Australian Health and Medical Research InstituteAdelaideSouth AustraliaAustralia
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Alyson Richard
- Microbiome and Host Health ProgramSouth Australian Health and Medical Research InstituteAdelaideSouth AustraliaAustralia
| | - Zhengyi Wang
- Medical SchoolThe University of Western AustraliaPerthWestern AustraliaAustralia
| | - Luis Calzadilla‐Bertot
- Medical SchoolThe University of Western AustraliaPerthWestern AustraliaAustralia
- Department of HepatologySir Charles Gairdner HospitalNedlandsWestern AustraliaAustralia
| | - Egi Vasil
- Microbiome and Host Health ProgramSouth Australian Health and Medical Research InstituteAdelaideSouth AustraliaAustralia
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Sophie Miller
- Microbiome and Host Health ProgramSouth Australian Health and Medical Research InstituteAdelaideSouth AustraliaAustralia
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Steven L. Taylor
- Microbiome and Host Health ProgramSouth Australian Health and Medical Research InstituteAdelaideSouth AustraliaAustralia
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Kerry L. Ivey
- Division of Aging, Department of MedicineBrigham and Women's HospitalBostonMassachusettsUSA
- Department of MedicineHarvard Medical SchoolBostonMassachusettsUSA
| | - Richard Woodman
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Brendan Adler
- Envision Medical ImagingWembleyWestern AustraliaAustralia
| | - Oyekoya T. Ayonrinde
- Medical SchoolThe University of Western AustraliaPerthWestern AustraliaAustralia
- Department of Gastroenterology and HepatologyFiona Stanley HospitalMurdochWestern AustraliaAustralia
- Medical SchoolCurtin UniversityBentleyWestern AustraliaAustralia
| | - John K. Olynyk
- Medical SchoolCurtin UniversityBentleyWestern AustraliaAustralia
| | - Lawrence J. Beilin
- Medical SchoolThe University of Western AustraliaPerthWestern AustraliaAustralia
| | - Trevor A. Mori
- Medical SchoolThe University of Western AustraliaPerthWestern AustraliaAustralia
| | - Alan J. Wigg
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
- South Australian Hepatology and Transplant Medicine UnitSouthern Adelaide Local Health NetworkBedford ParkSouth AustraliaAustralia
| | - Kate R. Muller
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
- South Australian Hepatology and Transplant Medicine UnitSouthern Adelaide Local Health NetworkBedford ParkSouth AustraliaAustralia
| | - Leon A. Adams
- Medical SchoolThe University of Western AustraliaPerthWestern AustraliaAustralia
- Department of HepatologySir Charles Gairdner HospitalNedlandsWestern AustraliaAustralia
| | - Geraint B. Rogers
- Microbiome and Host Health ProgramSouth Australian Health and Medical Research InstituteAdelaideSouth AustraliaAustralia
- Flinders Health and Medical Research Institute, College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
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5
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Nai S, Song J, Su W, Liu X. Bidirectional Interplay Among Non-Coding RNAs, the Microbiome, and the Host During Development and Diseases. Genes (Basel) 2025; 16:208. [PMID: 40004537 PMCID: PMC11855195 DOI: 10.3390/genes16020208] [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: 12/30/2024] [Revised: 01/24/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025] Open
Abstract
It is widely known that the dysregulation of non-coding RNAs (ncRNAs) and dysbiosis of the gut microbiome play significant roles in host development and the progression of various diseases. Emerging evidence has highlighted the bidirectional interplay between ncRNAs and the gut microbiome. This article aims to review the current understanding of the molecular mechanisms underlying the crosstalk between ncRNAs, especially microRNA (miRNA), and the gut microbiome in the context of development and diseases, such as colorectal cancer, inflammatory bowel diseases, neurological disorders, obesity, and cardiovascular disease. Ultimately, this review seeks to provide a foundation for exploring the potential roles of ncRNAs and gut microbiome interactions as biomarkers and therapeutic targets for clinical diagnosis and treatment, such as ncRNA mimics, antisense oligonucleotides, and small-molecule compounds, as well as probiotics, prebiotics, and diets.
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Affiliation(s)
| | | | | | - Xiaoqian Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (S.N.); (J.S.); (W.S.)
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6
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Xu Q, Wang W, Li Y, Cui J, Zhu M, Liu Y, Liu Y. The oral-gut microbiota axis: a link in cardiometabolic diseases. NPJ Biofilms Microbiomes 2025; 11:11. [PMID: 39794340 PMCID: PMC11723975 DOI: 10.1038/s41522-025-00646-5] [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: 02/18/2024] [Accepted: 12/29/2024] [Indexed: 01/13/2025] Open
Abstract
The oral-gut microbiota axis plays a crucial role in cardiometabolic health. This review explores the interactions between these microbiomes through enteric, hematogenous, and immune pathways, resulting in disruptions in microbial balance and metabolic processes. These disruptions contribute to systemic inflammation, metabolic disorders, and endothelial dysfunction, which are closely associated with cardiometabolic diseases. Understanding these interactions provides insights for innovative therapeutic strategies to prevent and manage cardiometabolic diseases.
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Affiliation(s)
- Qian Xu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Wenting Wang
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yiwen Li
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Jing Cui
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Mengmeng Zhu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yanfei Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
- The Second Department of Geriatrics, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
- Key Laboratory of Disease and Syndrome Integration Prevention and Treatment of Vascular Aging, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yue Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China.
- Key Laboratory of Disease and Syndrome Integration Prevention and Treatment of Vascular Aging, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China.
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7
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Göktürk K, Tülek B, Kanat F, Maçin S, Arslan U, Shahbazova M, Göktürk Ö. Gut microbiota profiles of patients with idiopathic pulmonary fibrosis. Exp Lung Res 2024; 50:278-289. [PMID: 39644491 DOI: 10.1080/01902148.2024.2437377] [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: 07/03/2024] [Revised: 11/26/2024] [Accepted: 11/28/2024] [Indexed: 12/09/2024]
Abstract
Purpose/Aim: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia. Multiple genetic factors, environmental exposures, micro-aspirations secondary to gastroesophageal reflux, age, sex, smoking habit, and infections contribute to its etiology; consequently, its pathogenesis remains unclear. The homeostasis of gut microbiota, including bacteria, archaea, and fungi, can influence the functions of both the intestine and remote organs. There are still many unknowns regarding the effects and mechanisms of gut microbiota dysbiosis on the development of IPF. In this study, we aimed to characterize the gut microbiota of patients with IPF compared with that of healthy controls. Furthermore, we assessed the effects of antifibrotic drugs on gut dysbiosis. Materials and Methods: This study involved 12 patients with IPF receiving antifibrotic drug therapy, 12 patients with IPF not receiving antifibrotic drug therapy, and 8 healthy controls. The clinical parameters of the patients were recorded, and DNA extracted from stool samples was subjected to 16S ribosomal RNA gene sequencing of the V1-V9 hypervariable regions. Results: Campylobacterota species were detected in the patient groups but not in the control group. Staphylococcales and Gemellaceae species were not detected in the IPF groups; however, a significant relationship was observed in the control group. In the IPF groups, Actinobacteria, Bifidobacteriales, Burkholderiales, Bacteroidaceae, Dorea, Fusicatenibacter, and Ruminococcus -gauvreauii abundance was low and Enterobacterales, Erysipelotrichaceae, Holdemanella, and Alloprevotella abundance was high compared with those in the control group. When the IPF group using antifibrotic drugs and that not using antifibrotic drugs were compared, only Lachnospiraceae UCG 004 abundance was found to be lower in the patient group receiving antifibrotic drugs. Conclusions: Patients with IPF exhibit higher or lower abundance of certain taxa compared to healthy controls, providing novel perspectives on the pathogenesis and treatment of various illnesses. Examining changes in intestinal microbiota during treatment may guide the clinical strategy for managing adverse effects.
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Affiliation(s)
- Kerim Göktürk
- Medicine Department of Chest Diseases, Ankara 29 May State Hospital, Ankara, Turkey
| | - Baykal Tülek
- Faculty of Medicine Department of Chest Diseases, Selcuk University, Konya, Turkey
| | - Fikret Kanat
- Faculty of Medicine Department of Chest Diseases, Selcuk University, Konya, Turkey
| | - Salih Maçin
- Faculty of Medicine Department of Microbiology, Selcuk University, Konya, Turkey
| | - Uğur Arslan
- Faculty of Medicine Department of Microbiology, Selcuk University, Konya, Turkey
| | - Masma Shahbazova
- Faculty of Medicine Department of Microbiology, Selcuk University, Konya, Turkey
| | - Özge Göktürk
- Medicine Department of Allergy Immunology, Sanatorium Atatürk Training and Research Hospital, Ankara, Turkey
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Zhong X, Yan J, Wei X, Xie T, Zhang Z, Wang K, Sun C, Chen W, Zhu J, Zhao X, Wang X. Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction. PHARMACEUTICAL BIOLOGY 2024; 62:1-12. [PMID: 38084911 PMCID: PMC11734889 DOI: 10.1080/13880209.2023.2289577] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 09/25/2023] [Accepted: 11/26/2023] [Indexed: 12/18/2023]
Abstract
CONTEXT Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear. OBJECTIVE We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles. MATERIALS AND METHODS Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days' administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed. RESULTS 0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%). DISCUSSION AND CONCLUSION The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.
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Affiliation(s)
- Xinqin Zhong
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Junyuan Yan
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xing Wei
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Tian Xie
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhaojian Zhang
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Kaiyue Wang
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Congying Sun
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wei Chen
- Hangzhou Hu Qing Yu Tang Pharmaceutical Co., Ltd, Hangzhou, China
| | - Jiaming Zhu
- Hangzhou Hu Qing Yu Tang Pharmaceutical Co., Ltd, Hangzhou, China
| | - Xin Zhao
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaoying Wang
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Jiang L, Liu P, Wang M, Deng Q, Wang J, Jiang Y, Zhu Y, Meng H, Lu X, Kong X, Chen L. Effect of high-intensity intermittent rehabilitation training on physical function, gut microbiome and metabolite after percutaneous coronary intervention in patients with coronary heart disease. Front Cardiovasc Med 2024; 11:1508456. [PMID: 39669411 PMCID: PMC11634878 DOI: 10.3389/fcvm.2024.1508456] [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: 10/09/2024] [Accepted: 11/18/2024] [Indexed: 12/14/2024] Open
Abstract
Background Postoperative rehabilitation exercise training after percutaneous coronary intervention (PCI) is crucial for coronary heart disease (CHD) patients in restoring health and preventing recurrence, including high-intensity interval training (HIIT). However, the impact of HIIT on cardiopulmonary function, gut microbiome and metabolite remains underexplored. Methods This study included 60 patients with CHD who underwent percutaneous coronary intervention (PCI). Participants were divided into two groups: 33 in the moderate-intensity continuous training (MCT) group and 27 in the high-intensity interval training (HIIT) group. We assessed difference between two training in cardiopulmonary function, 6-minute walk test (6MWT) performance, biochemical indicators, plasma metabolites, and gut microbiome feature at baseline and after 3 months training. Furthermore, we analyzed 6MWT association to gut microbiome and metabolites with group differences. Results The 6MWT showed significantly greater improvement in the HIIT group compared to the MCT group (P = 0.0024). Both groups showed reductions in low-density lipoprotein (LDL) levels and increases in peak oxygen uptake (VO2 peak) after training, but the HIIT group demonstrated a larger effect size in these measures. Moreover, subgroup analysis revealed that patients with a history of myocardial infarction (MI) in the HIIT group experienced a more substantial increase in VO2 peak compared to the MCT group (P = 0.04). In addition, we identified 29 gut microbial species and 30 plasma metabolites that were differentially enriched between the two groups, with some showing a significant impact on 6MWT performance. Conclusions High-intensity interval training significantly improves 6MWT performance and exercise tolerance in cardiac rehabilitation patients, particularly enhancing VO2 peak in those with a history of MI. HIIT also appears to modulate the gut microbiome, increasing the abundance of Clostridiales and decreasing traumatic acid content, which may contribute to the observed improvements in exercise tolerance.
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Affiliation(s)
- Lei Jiang
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Pu Liu
- Department of Cardiology, Yili Friendship Hospital, Yili Kazak Autonomous Prefecture, Yili, China
| | - Mei Wang
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qiufeng Deng
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiangpeng Wang
- Department of Cardiology, The Fifth People’s Hospital of Huaian, Huaian, China
| | - Yan Jiang
- Department of Rehabilitation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ye Zhu
- Department of Rehabilitation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Haoyu Meng
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiao Lu
- Department of Rehabilitation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiangqing Kong
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Leilei Chen
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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10
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Ichimura R, Tanaka K, Nakato G, Fukuda S, Arakawa K. Complete genome sequence of Mediterraneibacter gnavus strain RI1, isolated from human feces. Microbiol Resour Announc 2024; 13:e0086324. [PMID: 39345148 PMCID: PMC11556005 DOI: 10.1128/mra.00863-24] [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: 08/08/2024] [Accepted: 09/13/2024] [Indexed: 10/01/2024] Open
Abstract
We report the complete genome sequence of Mediterraneibacter gnavus strain RI1, a Gram-positive anaerobic gut microbe isolated from human feces. The complete circular genome has a genome size of 3.25 Mb, with a G+C content of 42.6%.
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Affiliation(s)
- Ryoha Ichimura
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
- Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa, Japan
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan
| | - Kazuki Tanaka
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
- Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa, Japan
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan
- Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo, Japan
| | - Gaku Nakato
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan
| | - Shinji Fukuda
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
- Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa, Japan
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan
- Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo, Japan
- Transborder Medical Research Center, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Kazuharu Arakawa
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
- Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa, Japan
- Faculty of Environment and Information Studies, Keio University, Fujisawa, Kanagawa, Japan
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11
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Bibi S, Kerbiriou C, Uzma, Mckirdy S, Kostrytsia A, Rasheed H, Eqani SAMAS, Gerasimidis K, Nurulain SM, Ijaz UZ. Gut microbiome and function are altered for individuals living in high fluoride concentration areas in Pakistan. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 284:116959. [PMID: 39232295 DOI: 10.1016/j.ecoenv.2024.116959] [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: 03/09/2024] [Revised: 08/16/2024] [Accepted: 08/26/2024] [Indexed: 09/06/2024]
Abstract
BACKGROUND Endemic fluorosis refers to the condition when individuals are exposed to excessive amounts of fluoride ion due to living in a region characterized by elevated levels of fluorine in the drinking water, food, and/or air. In Pakistan, a substantial proportion of the population is thereby affected, posing a public health concern. OBJECTIVES Assessing how the gut microbiota and its metabolic profiles are impacted by chronic exposure to fluoride in drinking water (that caused Dental Fluorosis) as well as to perceive how this microbiota is connected to adverse health outcomes prevailing with fluoride exposure. METHODS Drinking water (n=27) and biological samples (n=100) of blood, urine and feces were collected from 70 high fluoride exposed (with Dental Fluorosis) and 30 healthy control (without Dental Fluorosis) subjects. Water and urinary fluoride concentrations were determined. Serum/plasma biochemical testing was performed. Fecal DNA extraction, 16S rRNA analysis of microbial taxa, their predicted metabolic function and fecal short chain fatty acids (SCFAs) quantification were carried out. RESULTS The study revealed that microbiota taxonomic shifts and their metabolic characterization had been linked to certain host clinical parameters under the chronic fluoride exposure. Some sets of genera showed strong specificity to water and urine fluoride concentrations, Relative Fat Mass index and SCFAs. The SCFAs response in fluoride-exposed samples was observed to be correlated with bacterial taxa that could contribute to adverse health effects. CONCLUSIONS Microbial dysbiosis as a result of endemic fluorosis exhibits a structure that is associated with risk of metabolic deregulation and is implicated in various diseases. Our results may form the development of novel interventions and may have utility in diagnosis and monitoring.
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Affiliation(s)
- Sara Bibi
- Department of Biosciences, COMSATS University Islamabad, 45550, Pakistan; Water & Environment Research Group, University of Glasgow, Mazumdar-Shaw Advanced Research Centre, Glasgow G11 6EW, UK
| | - Caroline Kerbiriou
- School of Medicine, Dentistry & Nursing, Glasgow Royal Infirmary, Glasgow G31 2ER, UK
| | - Uzma
- Water & Environment Research Group, University of Glasgow, Mazumdar-Shaw Advanced Research Centre, Glasgow G11 6EW, UK
| | - Shona Mckirdy
- School of Medicine, Dentistry & Nursing, Glasgow Royal Infirmary, Glasgow G31 2ER, UK
| | - Anastasiia Kostrytsia
- Water & Environment Research Group, University of Glasgow, Mazumdar-Shaw Advanced Research Centre, Glasgow G11 6EW, UK
| | - Hifza Rasheed
- National Water Quality Laboratory, Pakistan Council of Research in Water Resources (PCRWR), Islamabad, Pakistan
| | | | | | | | - Umer Zeeshan Ijaz
- Water & Environment Research Group, University of Glasgow, Mazumdar-Shaw Advanced Research Centre, Glasgow G11 6EW, UK; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 7BE, UK; National University of Ireland, University Road, Galway H91 TK33, Ireland.
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12
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Dean YE, Shebl MA, Doma M, Elmezayen RW, Loayza Pintado JJ, Rouzan SS, Hassan NAIF, Yaqout YE, Tokunaga A, Anozie C, ElKoumi O, Elawady SS, Mady T, Nizam SN, Etman Y, Nizam R, Hazimeh Y, Alazmy M, Aiash H. Intestinal microbiome as a diagnostic marker of coronary artery disease: a systematic review and meta-analysis. Ann Med Surg (Lond) 2024; 86:6105-6120. [PMID: 39359774 PMCID: PMC11444608 DOI: 10.1097/ms9.0000000000002516] [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: 03/20/2024] [Accepted: 08/09/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND The intestinal microbiome has been recently linked to several metabolic and chronic disorders, one of which is coronary artery disease (CAD). Our study aimed to analyze the intestinal microbiome of CAD patients and assess the eligibility of dysbiosis as a diagnostic marker of CAD. METHODS PubMed, Scopus, Embase, and Web of Science were searched using terms, such as 'CAD' and 'microbiome'. Only observational controlled studies were included. R version 4.2.2 was used for the analysis. RESULTS A significant association was found between the CAD group and increased Simpson and Shannon Indices compared with the control group (MD=0.04, 95% CI=0.03-0.05, and MD=0.11, 95% CI=0.01-0.22, respectively). Our analysis yielded a statistically significant association between the CAD group and increased Prevotella genus (MD=13.27, 95% CI=4.12-22.42, P-value=0.004), Catenibacterium genus (MD=0.09, 95% CI=0.09-0.10), Pseudomonas genus (MD=0.54, 95% CI=0.29-0.78, P-value), and Subdoligranulum (MD=-0.06, 95% CI=-0.06 to -0.06) compared with the control group. Another significant association was detected between the CAD group and decreased Bacteroides vulgatus and Bacteroides dorei (MD=-10.31, 95% CI=-14.78 to -5.84, P-value <0.00001). CONCLUSION Dysbiosis is an acceptable diagnostic marker of CAD. Decreased B. dorei and B. vulgatus among CAD patients suggests a protective role of these bacteria. Future clinical trials are necessary to investigate the potential benefit of supplementation of these bacteria in treating or preventing CAD.
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Affiliation(s)
- Yomna E. Dean
- Alexandria University, Faculty of Medicine, Alexandria
| | | | - Mohamed Doma
- Alexandria University, Faculty of Medicine, Alexandria
| | | | | | | | | | | | | | | | - Omar ElKoumi
- Suez Universtiy, Faculty of Medicine, Suez, Egypt
| | | | - Tamer Mady
- International American University, College of Medicine, Saint Lucia
| | | | - Yasser Etman
- Texas Health Hospital Rockwall, Director of Intensive Care Unit, Rockwall, Texas, USA
| | | | - Yusef Hazimeh
- Lebanese University
- Zahraa Hospital, University Medical Center, Lebanon
| | | | - Hani Aiash
- Suez Universtiy, Faculty of Medicine, Suez, Egypt
- SUNY Upstate Medical University, Syracuse
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13
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Flores JA, Antonio JM, Suntornsaratoon P, Meadows V, Bandyopadhyay S, Han J, Singh R, Balasubramanian I, Upadhyay R, Liu Y, Bonder EM, Kiela P, Su X, Ferraris R, Gao N. The arginine and nitric oxide metabolic pathway regulate the gut colonization and expansion of Ruminococcous gnavus. J Biol Chem 2024; 300:107614. [PMID: 39089585 PMCID: PMC11387683 DOI: 10.1016/j.jbc.2024.107614] [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: 01/18/2024] [Revised: 07/08/2024] [Accepted: 07/11/2024] [Indexed: 08/04/2024] Open
Abstract
Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R. gnavus metabolites can modulate host intestinal physiology remains largely understudied. We performed untargeted metabolomic and bulk RNA-seq analyses using R. gnavus monocolonization in germ-free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R. gnavus in vitro and in nitric oxide synthase 2 (Nos2)-deficient mice. R. gnavus produces specific arginine, tryptophan, and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R. gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R. gnavus induced elevated levels of NOS2, while Nos2 ablation resulted in R. gnavus expansion in vivo. The growth of various R. gnavus strains can be inhibited by NO. Specific R. gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. Intestinal colonization and interaction with R. gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R. gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R. gnavus.
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Affiliation(s)
- Juan A Flores
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA
| | - Jayson M Antonio
- Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
| | - Panan Suntornsaratoon
- Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
| | - Vik Meadows
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
| | | | - Jiangmeng Han
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
| | - Rajbir Singh
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA
| | | | - Ravij Upadhyay
- Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
| | - Yue Liu
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA
| | - Edward M Bonder
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA
| | - Pawel Kiela
- Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children's Research Center, Department of Pediatrics, University of Arizona, Tucson, Arizona, USA
| | - Xiaoyang Su
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA
| | - Ronaldo Ferraris
- Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
| | - Nan Gao
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
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14
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Li C, Shu P, Shi T, Chen Y, Mei P, Zhang Y, Wang Y, Du X, Wang J, Zhang Y, Liu B, Sheng Z, Chan S, Dan Z. Predicting the potential deterioration of Barrett's esophagus based on gut microbiota: a Mendelian randomization analysis. Mamm Genome 2024; 35:399-413. [PMID: 38886201 DOI: 10.1007/s00335-024-10042-7] [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: 12/09/2023] [Accepted: 05/14/2024] [Indexed: 06/20/2024]
Abstract
Esophageal adenocarcinoma (EAC) is one of the most malignant tumors in the digestive system. To make thing worse, the scarcity of treatment options is disheartening. However, if detected early, there is a possibility of reversing the condition. Unfortunately, there is still a lack of relevant early screening methods. Considering that Barrett's esophagus (BE), a precursor lesion of EAC, has been confirmed as the only known precursor of EAC. Analyzing which BE cases will progress to EAC and understanding the processes and mechanisms involved is of great significance for early screening of such patients. Considering the significant alterations in the gut microbiota of patients with BE and its potential role in the progression to EAC, this study aims to analyze the relationship between BE, EAC, and GM to identify potential diagnostic biomarkers and therapeutic targets. This study utilized comprehensive statistical data on gut microbiota from a large-scale genome-wide association meta-analysis conducted by the MiBioGen consortium (n = 18,340). Subsequently, we selected a set of single nucleotide polymorphisms (SNPs) that fell below the genome-wide significance threshold (1 × 10-5) as instrumental variables. To investigate the causal relationship between gut microbiota and BE and EAC, we employed various MR analysis methods, including Inverse Variance Weighting (IVW), MR-Egger regression, weighted median (WM), and weighted mean. Additionally, we assessed the level of pleiotropy, heterogeneity, and stability of genetic variations through MR-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis. Furthermore, we conducted reverse MR analysis to identify the causal relationships between gut microbiota and BE and EAC. The results from the Inverse Variance-Weighted (IVW) analysis indicate that Alistipes (P = 4.86 × 10-2), Lactobacillus (P = 2.11 × 10-2), Prevotella 7 (P = 4.28 × 10-2), and RuminococcaceaeUCG004 (P = 4.34 × 10-2) are risk factors for Barrett's esophagus (BE), while Flavonifractor (P = 8.81 × 10-3) and RuminococcaceaeUCG004 (P = 4.99 × 10-2) are risk factors for esophageal adenocarcinoma (EAC). On the other hand, certain gut microbiota genera appear to have a protective effect against both BE and EAC. These include Eubacterium (nodatum group) (P = 4.51 × 10-2), Holdemania (P = 1.22 × 10-2), and Lactococcus (P = 3.39 × 10-2) in the BE cohort, as well as Eubacterium (hallii group) (P = 4.07 × 10-2) and Actinomyces (P = 3.62 × 10-3) in the EAC cohort. According to the results of reverse MR analysis, no significant causal effects of BE and EAC on gut microbiota were observed. Furthermore, no significant heterogeneity or pleiotropy was detected in the instrumental variables. We have established a causal relationship between the gut microbiota and BE and EAC. This study holds profound significance for screening BE patients who may be at risk of deterioration, as it can provide them with timely medical interventions to reverse the condition.
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Affiliation(s)
- Conghan Li
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Panyin Shu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, 610041, China
| | - Taiyu Shi
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Yuerong Chen
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Ping Mei
- Department of Radiology, Anqing Municipal Hospital, Anqing, Anhui Province, 246000, China
| | - Yizhong Zhang
- College of Anesthesia, Wannan Medical College, No. 22 Wenchang West Road, Yijiang District, Wuhu City, 241002, Anhui, China
| | - Yan Wang
- College of Life Sciences, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Xinyan Du
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Jianning Wang
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Yixin Zhang
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Bin Liu
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Zhijin Sheng
- Department of Physical Education, College of Humanistic Medicine, Anhui Medical University, Hefei, Anhui, China.
| | - Shixin Chan
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230032, China.
| | - Zhangyong Dan
- Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
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15
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Zhang C, Zhang Z, Zhang F, Zeng B, Liu X, Wang L. A computational model for potential microbe-disease association detection based on improved graph convolutional networks and multi-channel autoencoders. Front Microbiol 2024; 15:1435408. [PMID: 39144226 PMCID: PMC11322764 DOI: 10.3389/fmicb.2024.1435408] [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: 05/20/2024] [Accepted: 07/05/2024] [Indexed: 08/16/2024] Open
Abstract
Introduction Accumulating evidence shows that human health and disease are closely related to the microbes in the human body. Methods In this manuscript, a new computational model based on graph attention networks and sparse autoencoders, called GCANCAE, was proposed for inferring possible microbe-disease associations. In GCANCAE, we first constructed a heterogeneous network by combining known microbe-disease relationships, disease similarity, and microbial similarity. Then, we adopted the improved GCN and the CSAE to extract neighbor relations in the adjacency matrix and novel feature representations in heterogeneous networks. After that, in order to estimate the likelihood of a potential microbe associated with a disease, we integrated these two types of representations to create unique eigenmatrices for diseases and microbes, respectively, and obtained predicted scores for potential microbe-disease associations by calculating the inner product of these two types of eigenmatrices. Results and discussion Based on the baseline databases such as the HMDAD and the Disbiome, intensive experiments were conducted to evaluate the prediction ability of GCANCAE, and the experimental results demonstrated that GCANCAE achieved better performance than state-of-the-art competitive methods under the frameworks of both 2-fold and 5-fold CV. Furthermore, case studies of three categories of common diseases, such as asthma, irritable bowel syndrome (IBS), and type 2 diabetes (T2D), confirmed the efficiency of GCANCAE.
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Affiliation(s)
| | - Zhen Zhang
- Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha, China
| | | | | | - Xin Liu
- Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha, China
| | - Lei Wang
- Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha, China
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16
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Li Y, Yao M, Xie F, Qiu Y, Zhao X, Li R. Gut microbiota as a residual risk factor causally influencing cardiac structure and function: Mendelian randomization analysis and biological annotation. Front Microbiol 2024; 15:1410272. [PMID: 39132134 PMCID: PMC11316272 DOI: 10.3389/fmicb.2024.1410272] [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: 03/31/2024] [Accepted: 07/04/2024] [Indexed: 08/13/2024] Open
Abstract
Background The gut microbiota (GM) is widely acknowledged to have a significant impact on cardiovascular health and may act as a residual risk factor affecting cardiac structure and function. However, the causal relationship between GM and cardiac structure and function remains unclear. Objective This study aims to employ a two-sample Mendelian randomization (MR) approach to investigate the causal association between GM and cardiac structure and function. Methods Data on 119 GM genera were sourced from a genome-wide association study (GWAS) meta-analysis (13,266 European participants) conducted by the MiBioGen consortium, while data on 16 parameters of cardiac structure and function were obtained from the UK Biobank's GWAS of cardiac magnetic resonance imaging (up to 41,135 European participants). Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for causal association assessments, with sensitivity analyses conducted to reinforce the findings. Finally, biological annotation was performed on the GWAS data of GM and cardiac phenotypes with causal associations to explore potential mechanisms. Results The MR analysis, predominantly based on the IVW model, revealed 93 causal associations between the genetically predicted abundance of 44 GM genera and 16 cardiac structure and function parameters. These associations maintained consistent directions in MR-Egger and WM models, with no evidence of pleiotropy detected. Biological annotations suggest that GM may influence cardiac structure and function through pathways involved in myocardial cell development, cardiac contractility, and apoptosis. Conclusion The MR analysis supports a causal association between certain abundances of genetically predicted GM and cardiac structure and function, suggesting that GM could be a residual risk factor impacting cardiac phenotypes.
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Affiliation(s)
- Yihua Li
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Meidan Yao
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- National Key Laboratory of Chinese Medicine Evidence, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fei Xie
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yijun Qiu
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xinjun Zhao
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Rong Li
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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17
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Guan Y, Zhao S, Li J, Zhang W, Guo Z, Luo Y, Jiang X, Li J, Liu J, Chen X, Zhao Z, Zhang Z. Insights from metagenomics into gut microbiome associated with acute coronary syndrome therapy. Front Microbiol 2024; 15:1369478. [PMID: 39035441 PMCID: PMC11258018 DOI: 10.3389/fmicb.2024.1369478] [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: 01/12/2024] [Accepted: 06/14/2024] [Indexed: 07/23/2024] Open
Abstract
Acute coronary syndrome (ACS) is a predominant cause of mortality, and the prompt and precise identification of this condition is crucial to minimize its impact. Recent research indicates that gut microbiota is associated with the onset, progression, and treatment of ACS. To investigate its role, we sequenced the gut microbiota of 38 ACS patients before and after percutaneous coronary intervention and statin therapy at three time points, examining differential species and metabolic pathways. We observed a decrease in the abundance of Parabacteroides, Escherichia, and Blautia in patients after treatment and an increase in the abundance of Gemalla, Klebsiella variicola, Klebsiella pneumoniae, and others. Two pathways related to sugar degradation were more abundant in patients before treatment, possibly correlated with disorders of sugar metabolism and risk factors, such as hyperglycemia, insulin resistance, and insufficient insulin secretion. Additionally, seven pathways related to the biosynthesis of vitamin K2 and its homolog were reduced after treatment, suggesting that ACS patients may gradually recover after therapy. The gut microbiota of patients treated with different statins exhibited notable differences after treatment. Rosuvastatin appeared to promote the growth of anti-inflammatory bacteria while reducing pro-inflammatory bacteria, whereas atorvastatin may have mixed effects on pro-inflammatory and anti-inflammatory bacteria while increasing the abundance of Bacteroides. Our research will provide valuable insights and enhance comprehension of ACS, leading to better patient diagnosis and therapy.
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Affiliation(s)
- Yuee Guan
- Department of Cardiology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Shuru Zhao
- Shenzhen Byoryn Technology Co., Ltd., Shenzhen, China
| | - Jing Li
- University of Science and Technology of China, Hefei, China
| | - Wenqian Zhang
- Department of Cardiology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi'an, China
- Department of Computer Science, City University of Hong Kong, Kowloon Tong, China
| | - Zhonghao Guo
- School of Medicine, Xi’an Jiaotong University, Xi’an, China
| | - Yi Luo
- Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiaofei Jiang
- Department of Cardiology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Jun Li
- Department of Cardiology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Jianxiong Liu
- Department of Cardiology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Xi Chen
- Department of Cardiology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Zicheng Zhao
- Shenzhen Byoryn Technology Co., Ltd., Shenzhen, China
| | - Zhe Zhang
- Department of Cardiology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
- Department of Cardiology, The Zhuhai National Hi-tech Industrial Development District People’s Hospital (Zhuhai People’s Hospital Medical Group, High-tech Zone), Zhuhai, China
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18
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Thompson RS, Bowers SJ, Vargas F, Hopkins S, Kelley T, Gonzalez A, Lowry CA, Dorrestein PC, Vitaterna MH, Turek FW, Knight R, Wright KP, Fleshner M. A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose Produces Dynamic and Reproducible Changes in the Gut Microbial Ecosystem in Male Rats. Nutrients 2024; 16:1790. [PMID: 38892722 PMCID: PMC11175065 DOI: 10.3390/nu16111790] [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: 05/07/2024] [Revised: 05/30/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024] Open
Abstract
Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbially modified metabolites over time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides (GOS) and polydextrose (PDX)), compared to a control diet, would consistently impact the gut microbiome and microbially modified bile acids over time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiomes and metabolomes were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered the beta diversity, relative abundance of bacterial genera, and microbially modified bile acids over time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by the prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbially modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites, supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.
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Affiliation(s)
- Robert S. Thompson
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Samuel J. Bowers
- Department of Neurobiology, Northwestern University, Center for Sleep and Circadian Biology, Evanston, IL 60208, USA; (S.J.B.); (M.H.V.); (F.W.T.)
| | - Fernando Vargas
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA 92093, USA (P.C.D.)
| | - Shelby Hopkins
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Tel Kelley
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
| | - Antonio Gonzalez
- Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA (R.K.)
| | - Christopher A. Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Pieter C. Dorrestein
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA 92093, USA (P.C.D.)
| | - Martha Hotz Vitaterna
- Department of Neurobiology, Northwestern University, Center for Sleep and Circadian Biology, Evanston, IL 60208, USA; (S.J.B.); (M.H.V.); (F.W.T.)
| | - Fred W. Turek
- Department of Neurobiology, Northwestern University, Center for Sleep and Circadian Biology, Evanston, IL 60208, USA; (S.J.B.); (M.H.V.); (F.W.T.)
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA (R.K.)
- Department of Computer Science and Engineering, University of California San Diego, San Diego, CA 92093, USA
- Center for Microbiome Innovation, University of California San Diego, San Diego, CA 92093, USA
| | - Kenneth P. Wright
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Monika Fleshner
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
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19
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Fan P, Ding L, Du G, Wei C. Effect of mastectomy on gut microbiota and its metabolites in patients with breast cancer. Front Microbiol 2024; 15:1269558. [PMID: 38860221 PMCID: PMC11163111 DOI: 10.3389/fmicb.2024.1269558] [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: 07/31/2023] [Accepted: 04/30/2024] [Indexed: 06/12/2024] Open
Abstract
Background The relationship between gut microbiota and breast cancer has been extensively studied; however, changes in gut microbiota after breast cancer surgery are still largely unknown. Materials and methods A total of 20 patients with breast cancer underwent routine open surgery at the First Affiliated Hospital of Hainan Medical College from 1 June 2022 to 1 December 2022. Stool samples were collected from the patients undergoing mastectomy for breast cancer preoperatively, 3 days later, and 7 days later postoperatively. The stool samples were subjected to 16s rRNA sequencing. Results Surgery did not affect the α-diversity of gut microbiota. The β-diversity and composition of gut microorganisms were significantly affected by surgery in breast cancer patients. Both linear discriminant analysis effect size (LEfSe) analysis and between-group differences analysis showed that surgery led to a decrease in the abundance of Firmicutes and Lachnospiraceae and an increase in the abundance of Proteobacteria and Enterobacteriaceae. Moreover, 127 differential metabolites were screened and classified into 5 categories based on their changing trends. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed significant changes in the phenylalanine metabolic pathway and exogenous substance metabolic pathway. Eight characterized metabolites were screened using ROC analysis. Conclusion Our study found that breast cancer surgery significantly altered gut microbiota composition and metabolites, with a decrease in beneficial bacteria and an increase in potentially harmful bacteria. This underscores the importance of enhanced postoperative management to optimize gut microbiota.
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Affiliation(s)
- Pingming Fan
- Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Linwei Ding
- Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China
| | - Guankui Du
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
- Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China
| | - Changyuan Wei
- Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
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20
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Dinetz E, Zeballos-Palacios C, Martinez CA. Addressing the Missing Links in Cardiovascular Aging. Clin Interv Aging 2024; 19:873-882. [PMID: 38774249 PMCID: PMC11107914 DOI: 10.2147/cia.s457180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 04/27/2024] [Indexed: 05/24/2024] Open
Abstract
The aim of this manuscript is to provide a review of available options to enhance cardiovascular health and prevent cardiovascular disease (CVD) in the aging population using a systems-biology approach. These include the role of the gut microbiome, the early identification and removal of environmental toxins, and finally age related sex hormones and supplement replacement which all influence aging. Implementing such a comprehensive approach has the potential to facilitate earlier risk assessment, disease prevention, and even improve mortality. Further study in these areas will continue to advance our understanding and refine therapeutic interventions for a healthier cardiovascular aging process.
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Affiliation(s)
- Elliot Dinetz
- Department of Integrative and Family Medicine, University of Miami Miller School of Medicine Miami, Miami, FL, USA
| | | | - Claudia A Martinez
- Department of Medicine, Cardiovascular Division, University of Miami Miller School of Medicine, Miami, FL, USA
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21
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Baron M, Zuo B, Chai J, Zhao J, Jahan-Mihan A, Ochrietor J, Arikawa AY. The effects of fermented vegetables on the gut microbiota for prevention of cardiovascular disease. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2024; 5:e6. [PMID: 39290661 PMCID: PMC11404656 DOI: 10.1017/gmb.2024.4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 10/24/2023] [Accepted: 04/10/2024] [Indexed: 09/19/2024]
Abstract
This study investigated the impact of regular consumption of fermented vegetables (FVs) on inflammation and the composition of the gut microbiota in adults at increased risk for cardiovascular disease. Eighty-seven adults ages 35-64 were randomized into an FV group, who consumed 100 g FVs daily at least five times per week for eight weeks, or a usual diet (UD) group. Blood and stool samples were obtained before and after the intervention. Dependent samples t tests and adjusted linear models were used for within- and between-group comparisons. The mean age and body mass index of participants were 45 years and 30 kg/m2, and 80% were female. Bloating or gas was the most common side effect reported (19.3% FV group vs. 9.4% UD group). There were no changes in C-reactive protein, oxidized low-density lipoprotein-receptor 1, angiopoietin-like protein 4, trimethylamine oxide, and lipopolysaccharide-binding protein or bacterial alpha diversity between groups. Our findings indicate that consuming 100 g of FVs for at least five days per week for eight weeks does not change inflammatory biomarkers or microbial alpha diversity as measured by the Shannon index. It is possible that higher doses of FVs are necessary to elicit a significant response by gut bacteria.
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Affiliation(s)
- Melissa Baron
- Instructor of Nutrition and Dietetics, University of North Florida, Jacksonville, FL, USA
| | - Bin Zuo
- Research Assistant of Animal Science, University of Arkansas, Fayetteville, AR, USA
| | - Jianmin Chai
- Schoo of Life Sciences, University of Foshan, Foshan, China
| | - Jiangchao Zhao
- Animal Science, University of Arkansas, Fayetteville, AR, USA
| | | | - Judy Ochrietor
- Biology, University of North Florida, Jacksonville, FL, USA
| | - Andrea Y Arikawa
- Nutrition and Dietetics, University of North Florida, Jacksonville, FL, USA
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22
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Li L, He S, Liao B, Wang M, Lin H, Hu B, Lan X, Shu Z, Zhang C, Yu M, Zou Z. Orally Administrated Hydrogel Harnessing Intratumoral Microbiome and Microbiota-Related Immune Responses for Potentiated Colorectal Cancer Treatment. RESEARCH (WASHINGTON, D.C.) 2024; 7:0364. [PMID: 38721274 PMCID: PMC11077293 DOI: 10.34133/research.0364] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 04/02/2024] [Indexed: 10/08/2024]
Abstract
The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments. The antibacterial or tumor microenvironment (TME)-modulating approaches have been shown to markedly improve antitumor efficacy, strategies focused on normalizing the microbial environment are rarely reported. Here, we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects, containing hollow MnO2 nanocarrier loaded with the chemotherapeutic drug Oxa (Oxa@HMI). On the one hand, beneficial bacteria in the colon specifically metabolized Oxa@HMI, resulting in the degradation of inulin and the generation of short-chain fatty acids (SCFAs). These SCFAs play a crucial role in modulating microbiota and stimulating immune responses. On the other hand, the hydrogel matrix underwent colon microbiota-specific degradation, enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME. In this study, we have established, for the first time, a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention. Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue, providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.
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Affiliation(s)
- Lei Li
- Department of General Surgery, Zhujiang Hospital,
Southern Medical University, Guangzhou 510282, China
| | - Shouhua He
- Department of General Surgery, Zhujiang Hospital,
Southern Medical University, Guangzhou 510282, China
| | - Boyi Liao
- Department of General Surgery, Zhujiang Hospital,
Southern Medical University, Guangzhou 510282, China
| | - Manchun Wang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences,
Southern Medical University, Guangzhou 510515, China
| | - Huimin Lin
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences,
Southern Medical University, Guangzhou 510515, China
| | - Ben Hu
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences,
Southern Medical University, Guangzhou 510515, China
| | - Xinyue Lan
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences,
Southern Medical University, Guangzhou 510515, China
| | - Zhilin Shu
- Department of General Surgery, Zhujiang Hospital,
Southern Medical University, Guangzhou 510282, China
| | - Chao Zhang
- Department of General Surgery, Zhujiang Hospital,
Southern Medical University, Guangzhou 510282, China
| | - Meng Yu
- Department of General Surgery, Zhujiang Hospital,
Southern Medical University, Guangzhou 510282, China
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences,
Southern Medical University, Guangzhou 510515, China
| | - Zhaowei Zou
- Department of General Surgery, Zhujiang Hospital,
Southern Medical University, Guangzhou 510282, China
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23
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Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, Vázquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, Méric G, Inouye M. Integration of polygenic and gut metagenomic risk prediction for common diseases. NATURE AGING 2024; 4:584-594. [PMID: 38528230 PMCID: PMC11031402 DOI: 10.1038/s43587-024-00590-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 02/13/2024] [Indexed: 03/27/2024]
Abstract
Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.
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Affiliation(s)
- Yang Liu
- Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
- Department of Clinical Pathology, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia.
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
| | - Scott C Ritchie
- Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- British Heart Foundation Cambridge Centre of Research Excellence, School of Clinical Medicine, University of Cambridge, Cambridge, UK
- Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK
| | - Shu Mei Teo
- Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia
| | - Matti O Ruuskanen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Department of Computing, University of Turku, Turku, Finland
| | - Oleg Kambur
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Qiyun Zhu
- School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA
| | - Jon Sanders
- Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY, USA
| | - Yoshiki Vázquez-Baeza
- Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA
| | - Karin Verspoor
- School of Computing Technologies, RMIT University, Melbourne, Victoria, Australia
- School of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia
| | - Pekka Jousilahti
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Leo Lahti
- Department of Computing, University of Turku, Turku, Finland
| | - Teemu Niiranen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland
| | - Veikko Salomaa
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Aki S Havulinna
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Institute for Molecular Medicine Finland, FIMM-HiLIFE, University of Helsinki, Helsinki, Finland
| | - Rob Knight
- Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Guillaume Méric
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Central Clinical School, Monash University, Melbourne, Victoria, Australia
- Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia
- Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Melbourne, Victoria, Australia
- Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden
| | - Michael Inouye
- Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
- Department of Clinical Pathology, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia.
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
- British Heart Foundation Cambridge Centre of Research Excellence, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
- Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
- The Alan Turing Institute, London, UK.
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24
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Trøseid M, Molinaro A, Gelpi M, Vestad B, Kofoed KF, Fuchs A, Køber L, Holm K, Benfield T, Ueland PM, Hov JR, Nielsen SD, Knudsen AD. Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV. J Infect Dis 2024; 229:898-907. [PMID: 38195204 PMCID: PMC10938217 DOI: 10.1093/infdis/jiad604] [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: 09/28/2023] [Revised: 12/13/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases. METHODS Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114). RESULTS Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.2; P = .048). CONCLUSIONS PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.
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Affiliation(s)
- Marius Trøseid
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Antonio Molinaro
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Marco Gelpi
- Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Beate Vestad
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Klaus Fuglsang Kofoed
- Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Radiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Fuchs
- Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Lars Køber
- Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Kristian Holm
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Thomas Benfield
- Department of Infectious Diseases, Copenhagen University Hospital—Amager and Hvidovre, Hvidovre, Denmark
| | | | - Johannes R Hov
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Susanne Dam Nielsen
- Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen Copenhagen, Denmark
| | - Andreas Dehlbæk Knudsen
- Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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25
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Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med 2024; 19:275-293. [PMID: 37505311 PMCID: PMC10954893 DOI: 10.1007/s11739-023-03374-w] [Citation(s) in RCA: 268] [Impact Index Per Article: 268.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 07/10/2023] [Indexed: 07/29/2023]
Abstract
The intestine is the largest interface between the internal body and the external environment. The intestinal barrier is a dynamic system influenced by the composition of the intestinal microbiome and the activity of intercellular connections, regulated by hormones, dietary components, inflammatory mediators, and the enteric nervous system (ENS). Over the years, it has become increasingly evident that maintaining a stable intestinal barrier is crucial to prevent various potentially harmful substances and pathogens from entering the internal environment. Disruption of the barrier is referred to as 'leaky gut' or leaky gut wall syndrome and seems to be characterized by the release of bacterial metabolites and endotoxins, such as lipopolysaccharide (LPS), into the circulation. This condition, mainly caused by bacterial infections, oxidative stress, high-fat diet, exposure to alcohol or chronic allergens, and dysbiosis, appear to be highly connected with the development and/or progression of several metabolic and autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, inflammatory bowel disease, and type 1 diabetes mellitus (T1D). In this review, starting from a description of the mechanisms that enable barrier homeostasis and analyzing the relationship between this complex ecosystem and various pathological conditions, we explore the role of the gut barrier in driving systemic inflammation, also shedding light on current and future therapeutic interventions.
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Affiliation(s)
- Federica Di Vincenzo
- UOS Malattie Infiammatorie Croniche Intestinali, Centro Malattie Apparato Digerente (CeMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, L.go A. Gemelli 8, Rome, Italy.
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome, Italy.
| | - Angelo Del Gaudio
- UOS Malattie Infiammatorie Croniche Intestinali, Centro Malattie Apparato Digerente (CeMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, L.go A. Gemelli 8, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome, Italy
| | - Valentina Petito
- UOS Malattie Infiammatorie Croniche Intestinali, Centro Malattie Apparato Digerente (CeMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, L.go A. Gemelli 8, Rome, Italy
| | - Loris Riccardo Lopetuso
- UOS Malattie Infiammatorie Croniche Intestinali, Centro Malattie Apparato Digerente (CeMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, L.go A. Gemelli 8, Rome, Italy
| | - Franco Scaldaferri
- UOS Malattie Infiammatorie Croniche Intestinali, Centro Malattie Apparato Digerente (CeMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, L.go A. Gemelli 8, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome, Italy
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26
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Mostafa RH, Moustafa A. Beyond acute infection: molecular mechanisms underpinning cardiovascular complications in long COVID. Front Cardiovasc Med 2024; 11:1268571. [PMID: 38495940 PMCID: PMC10942004 DOI: 10.3389/fcvm.2024.1268571] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 01/29/2024] [Indexed: 03/19/2024] Open
Abstract
SARS-CoV-2, responsible for the global COVID-19 pandemic, has manifested significant cardiovascular implications for the infected population. These cardiovascular repercussions not only linger beyond the initial phase of illness but have also been observed in individuals who remain asymptomatic. This extended and pervasive impact is often called the post-acute COVID-19 syndrome (PACS) or "Long COVID". With the number of confirmed global cases approaching an alarming 756 million, the multifaceted challenges of Long COVID are undeniable. These challenges span from individual health complications to considerable burdens on worldwide healthcare systems. Our review comprehensively examines the complications of the persistent cardiovascular complications associated with COVID-19. Furthermore, we shed light on emerging therapeutic strategies that promise to manage and possibly mitigate these complications. We also introduce and discuss the profound concerns regarding the potential transgenerational repercussions of SARS-CoV-2, emphasizing the need for a proactive and informed approach to future research and clinical practice.
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Affiliation(s)
- Roba Hamed Mostafa
- Systems Genomics Laboratory, American University in Cairo, New Cairo, Egypt
- Biotechnology Graduate Program, American University in Cairo, New Cairo, Egypt
| | - Ahmed Moustafa
- Systems Genomics Laboratory, American University in Cairo, New Cairo, Egypt
- Biotechnology Graduate Program, American University in Cairo, New Cairo, Egypt
- Department of Biology, American University in Cairo, New Cairo, Egypt
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27
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Imdad S, So B, Jang J, Park J, Lee SJ, Kim JH, Kang C. Temporal variations in the gut microbial diversity in response to high-fat diet and exercise. Sci Rep 2024; 14:3282. [PMID: 38332014 PMCID: PMC10853223 DOI: 10.1038/s41598-024-52852-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 01/24/2024] [Indexed: 02/10/2024] Open
Abstract
High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and cardiovascular diseases. In contrast, exercise can positively influence gut microbial diversity and is linked to a decreased inflammatory state. To understand the gut microbial variations associated with exercise and high-fat diet over time, we conducted a longitudinal study to examine the effect of covariates on gut microbial diversity and composition. Young mice were divided into four groups: Chow-diet (CHD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise only (EXE) and underwent experimental intervention for 12 weeks. Fecal samples at week 0 and 12 were collected for DNA extraction, followed by 16S library preparation and sequencing. Data were analyzed using QIIME 2, R and MicrobiomeAnalyst. The Bacteroidetes-to-Firmicutes ratio decreased fivefold in the HFD and HFX groups compared to that in the CHD and EXE groups and increased in the EXE group over time. Alpha diversity was significantly increased in the EXE group longitudinally (p < 0.02), whereas diversity (Shannon, Faith's PD, and Fisher) and richness (ACE) was significantly reduced in the HFD (p < 0.005) and HFX (p < 0.03) groups over time. Beta diversity, based on the Jaccard, Bray-Curtis, and unweighted UniFrac distance metrics, was significant among the groups. Prevotella, Paraprevotella, Candidatus arthromitus, Lactobacillus salivarius, L. reuteri, Roseburia, Bacteroides uniformis, Sutterella, and Corynebacterium were differentially abundant in the chow-diet groups (CHD and EXE). Exercise significantly reduced the proportion of taxa characteristic of a high-fat diet, including Butyricimonas, Ruminococcus gnavus, and Mucispirillum schaedleri. Diet, age, and exercise significantly contributed to explaining the bacterial community structure and diversity in the gut microbiota. Modulating the gut microbiota and maintaining its stability can lead to targeted microbiome therapies to manage chronic and recurrent diseases and infections.
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Affiliation(s)
- Saba Imdad
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Sport Science Research Institute, Inha University, Incheon, 22212, South Korea
- Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Cheongju, 28503, South Korea
| | - Byunghun So
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Sport Science Research Institute, Inha University, Incheon, 22212, South Korea
| | - Junho Jang
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Sport Science Research Institute, Inha University, Incheon, 22212, South Korea
| | - Jinhan Park
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Sport Science Research Institute, Inha University, Incheon, 22212, South Korea
| | - Sam-Jun Lee
- Department of Sport Rehabilitation, College of Health, Welfare, and Education, Tong Myong University, Busan, 48520, South Korea
| | - Jin-Hee Kim
- Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Cheongju, 28503, South Korea.
| | - Chounghun Kang
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Sport Science Research Institute, Inha University, Incheon, 22212, South Korea.
- Department of Physical Education, College of Education, Inha University, Incheon, 22212, South Korea.
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28
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Erawijantari PP, Kartal E, Liñares-Blanco J, Laajala TD, Feldman LE, Carmona-Saez P, Shigdel R, Claesson MJ, Bertelsen RJ, Gomez-Cabrero D, Minot S, Albrecht J, Chung V, Inouye M, Jousilahti P, Schultz JH, Friederich HC, Knight R, Salomaa V, Niiranen T, Havulinna AS, Saez-Rodriguez J, Levinson RT, Lahti L. Microbiome-based risk prediction in incident heart failure: a community challenge. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.10.12.23296829. [PMID: 37873403 PMCID: PMC10593042 DOI: 10.1101/2023.10.12.23296829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
Heart failure (HF) is a major public health problem. Early identification of at-risk individuals could allow for interventions that reduce morbidity or mortality. The community-based FINRISK Microbiome DREAM challenge (synapse.org/finrisk) evaluated the use of machine learning approaches on shotgun metagenomics data obtained from fecal samples to predict incident HF risk over 15 years in a population cohort of 7231 Finnish adults (FINRISK 2002, n=559 incident HF cases). Challenge participants used synthetic data for model training and testing. Final models submitted by seven teams were evaluated in the real data. The two highest-scoring models were both based on Cox regression but used different feature selection approaches. We aggregated their predictions to create an ensemble model. Additionally, we refined the models after the DREAM challenge by eliminating phylum information. Models were also evaluated at intermediate timepoints and they predicted 10-year incident HF more accurately than models for 5- or 15-year incidence. We found that bacterial species, especially those linked to inflammation, are predictive of incident HF. This highlights the role of the gut microbiome as a potential driver of inflammation in HF pathophysiology. Our results provide insights into potential modeling strategies of microbiome data in prospective cohort studies. Overall, this study provides evidence that incorporating microbiome information into incident risk models can provide important biological insights into the pathogenesis of HF.
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Affiliation(s)
| | - Ece Kartal
- Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
| | - José Liñares-Blanco
- Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
- GENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain
- Department of Statistics and Operations Research, University of Granada, Spain
| | - Teemu D Laajala
- Department of Mathematics and Statistics, Faculty of Science, University of Turku, Finland
- Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Lily Elizabeth Feldman
- Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Pedro Carmona-Saez
- GENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain
- Department of Statistics and Operations Research, University of Granada, Spain
| | - Rajesh Shigdel
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Marcus Joakim Claesson
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland
- School of Microbiology, University College Cork, T12 YT20 Cork, Ireland
| | | | - David Gomez-Cabrero
- Translational Bioinformatics Unit, Navarrabiomed, Public University of Navarra, IDISNA, Pamplona, Spain
- Biological and Environmental Sciences & Engineering Division, King Abdullah University of Science & Technology, Thuwal, Kingdom of Saudi Arabia
| | - Samuel Minot
- Data Core, Shared Resources, Fred Hutchinson Cancer Center. Seattle, WA. USA
| | | | | | - Michael Inouye
- Cambridge Baker Systems Genomics Initiative, Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia
- Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, Cambridge University, Cambridge, UK
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
| | - Pekka Jousilahti
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Jobst-Hendrik Schultz
- Department of General Internal Medicine & Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
| | - Hans-Christoph Friederich
- Department of General Internal Medicine & Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
| | - Rob Knight
- Jacobs School of Engineering, University of California San Diego, La Jolla, CA. USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA. USA
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA. USA
- Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA. USA
| | - Veikko Salomaa
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Teemu Niiranen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
- Department of Internal Medicine, University of Turku, Turku, Finland
| | - Aki S Havulinna
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, Helsinki, Finland
| | - Julio Saez-Rodriguez
- Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
| | - Rebecca T Levinson
- Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
- Department of General Internal Medicine & Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
| | - Leo Lahti
- Department of Computing, Faculty of Technology, University of Turku, Turku, Finland
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Yoo JY, McSkimming D, Rajan K, Sarkar A, Labbé N, Groer M, Menon U. A Preliminary Study Exploring the Relationship between Occupational Health Hazards and Gut Microbiota among Firefighters. Life (Basel) 2023; 13:1928. [PMID: 37763331 PMCID: PMC10533145 DOI: 10.3390/life13091928] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/11/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
Firefighters are exposed to occupational hazards and have a higher prevalence of health issues. The gut microbiota plays a crucial role in the immune, endocrine, and neural systems, and disruptions in its composition can impact health outcomes. This pilot study aimed to investigate the potential association between occupational factors, changes in gut microbiota, and the development of adverse health outcomes in firefighters. To test this hypothesis, we recruited 15 firefighters and age/sex-matched controls to investigate the relationship between occupational environment and gut microbiota. Firefighters exhibit lower intestinal bacterial alpha diversity and a higher presence of pathogenic bacteria than the control. Moreover, unique gut bacterial taxa were observed in firefighters with high post-traumatic stress disorder (PTSD) scores, which could contribute to immune dysregulation and higher susceptibility to pathogen colonization. These preliminary findings suggest that occupational factors, including exposure to traumatic stressors and chemicals, may influence firefighters' health by modulating their gut microbiota. The observed changes in gut microbiota composition and the potential link to occupational hazards highlight the need for further research in larger sample-size studies. Understanding the role of gut microbiota in firefighter health may have implications for preventive measures and interventions to mitigate occupational health risks and improve overall well-being.
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Affiliation(s)
- Ji Youn Yoo
- College of Nursing, University of Tennessee Knoxville, Knoxville, TN 37996, USA; (A.S.); (M.G.)
| | - Daniel McSkimming
- Interdisciplinary Unit in Data Science & Analytics, Buffalo State University, Buffalo, NY 14222, USA;
| | - Kalavathy Rajan
- Department of Plant and Soil Science, Fiber and Biopolymer Research Institute, Texas Tech University, Lubbock, TX 79403, USA;
| | - Anujit Sarkar
- College of Nursing, University of Tennessee Knoxville, Knoxville, TN 37996, USA; (A.S.); (M.G.)
| | - Nicole Labbé
- Center for Renewable Carbon, The University of Tennessee Institute of Agriculture, Knoxville, TN 37996, USA;
| | - Maureen Groer
- College of Nursing, University of Tennessee Knoxville, Knoxville, TN 37996, USA; (A.S.); (M.G.)
| | - Usha Menon
- College of Nursing, University of South Florida, Tampa, FL 33612, USA;
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30
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Cuadrat RRC, Goris T, Birukov A, Eichelmann F, Andrade BGN, Bang C, Franke A, Wittenbecher C, Schulze MB. Association of the human gut microbiota with vascular stiffness. Sci Rep 2023; 13:13348. [PMID: 37587126 PMCID: PMC10432492 DOI: 10.1038/s41598-023-40178-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 08/06/2023] [Indexed: 08/18/2023] Open
Abstract
Gut microbiota metabolites have been mechanistically linked to inflammatory pathway activation and atherosclerosis, which are major causes of vascular stiffness (VS). Aiming to investigate if the gut microbiome might be involved in VS development, we performed a cross-sectional study (n = 3,087), nested within the population-based European Prospective Investigations into Cancer and Nutrition (EPIC) Potsdam. We investigated the correlation of the gut microbiota (alpha diversity and taxa abundance) with 3 vascular stiffness measures: carotid-femoral (PWV), aortic augmentation index (AIX) and ankle-brachial index (ABI). Shannon index was not significantly associated with VS but the number of observed Amplicon Sequence Variants (ASV) was positively associated with PWV and AIX. We found a total of 19 ASVs significantly associated with at least one VS measure in multivariable-adjusted models. One ASV (classified as Sutterella wadsworthensis) was associated with 2 VS measures, AIX (- 0.11 ± 0.04) and PWV (-0.14 ± 0.03). Other examples of ASVs associated with VS were Collinsella aerofaciens, previously reported to be affected by diet and Bacteroides uniformis, commercially available as probiotics. In conclusion, our study suggests a potential role of individual components of the gut microbiota in the aetiology of VS.
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Affiliation(s)
- Rafael R C Cuadrat
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Bioinformatics and Omics Data Science, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center (MDC), Berlin, Germany
| | - Tobias Goris
- Research Group Intestinal Microbiology, Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
| | - Anna Birukov
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Fabian Eichelmann
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Bruno G N Andrade
- Department of Computer Science, Munster Technological University, MTU/ADAPT, Cork, Ireland
| | - Corinna Bang
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Clemens Wittenbecher
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
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31
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Bui TVA, Hwangbo H, Lai Y, Hong SB, Choi YJ, Park HJ, Ban K. The Gut-Heart Axis: Updated Review for The Roles of Microbiome in Cardiovascular Health. Korean Circ J 2023; 53:499-518. [PMID: 37525495 PMCID: PMC10435824 DOI: 10.4070/kcj.2023.0048] [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: 04/25/2023] [Accepted: 05/19/2023] [Indexed: 08/02/2023] Open
Abstract
Cardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD. In addition, increasing evidence has demonstrated the alterations in the ratio of Firmicutes to Bacteroidetes and the imbalance of microbial-dependent metabolites, including short-chain fatty acids and trimethylamine N-oxide, play a crucial role in the pathogenesis of CVD. However, the exact mechanism of action remains undefined to this day. In this review, we focus on the compositional changes in the gut microbiome and its related metabolites in various CVDs. Moreover, the potential treatment and preventive strategies targeting the gut microbiome and its metabolites are discussed.
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Affiliation(s)
- Thi Van Anh Bui
- Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong SAR
- Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong SAR
| | - Hyesoo Hwangbo
- Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong SAR
- Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong SAR
| | - Yimin Lai
- Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong SAR
- Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong SAR
| | - Seok Beom Hong
- Department of Thoracic and Cardiovascular Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yeon-Jik Choi
- Division of Cardiology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hun-Jun Park
- Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| | - Kiwon Ban
- Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong SAR
- Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong SAR.
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32
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Belli M, Barone L, Longo S, Prandi FR, Lecis D, Mollace R, Margonato D, Muscoli S, Sergi D, Federici M, Barillà F. Gut Microbiota Composition and Cardiovascular Disease: A Potential New Therapeutic Target? Int J Mol Sci 2023; 24:11971. [PMID: 37569352 PMCID: PMC10418329 DOI: 10.3390/ijms241511971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/13/2023] [Accepted: 07/24/2023] [Indexed: 08/13/2023] Open
Abstract
A great deal of evidence has revealed an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these metabolites, the most important is Trimethylamine N-Oxide (TMAO), which is responsible, through various mechanisms, for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with respect to HF, and the possible strategies for influencing its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and a new therapeutic target for HF.
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Affiliation(s)
- Martina Belli
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (M.B.)
- Cardiovascular Imaging Unit, San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Lucy Barone
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (M.B.)
| | - Susanna Longo
- Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy (R.M.)
| | - Francesca Romana Prandi
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (M.B.)
- Division of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA
| | - Dalgisio Lecis
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (M.B.)
| | - Rocco Mollace
- Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy (R.M.)
- Cardiovascular Department, Humanitas Gavazzeni, 24125 Bergamo, Italy
| | - Davide Margonato
- Cardiovascular Imaging Unit, San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Saverio Muscoli
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (M.B.)
| | - Domenico Sergi
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (M.B.)
| | - Massimo Federici
- Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy (R.M.)
| | - Francesco Barillà
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (M.B.)
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33
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Fardi F, Bahari Khasraghi L, Shahbakhti N, Salami Naseriyan A, Najafi S, Sanaaee S, Alipourfard I, Zamany M, Karamipour S, Jahani M, Majidpoor J, Kalhor K, Talebi M, Mohsen Aghaei-Zarch S. An interplay between non-coding RNAs and gut microbiota in human health. Diabetes Res Clin Pract 2023:110739. [PMID: 37270071 DOI: 10.1016/j.diabres.2023.110739] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 04/22/2023] [Accepted: 05/30/2023] [Indexed: 06/05/2023]
Abstract
Humans have a complicated symbiotic relationship with their gut microbiome, which is postulated to impact host health and disease broadly. Epigenetic alterations allow host cells to regulate gene expression without altering the DNA sequence. The gut microbiome, offering environmental hints, can influence responses to stimuli by host cells with modifications on their epigenome and gene expression. Recent increasing data suggest that regulatory non-coding RNAs (miRNAs, circular RNAs, and long lncRNA) may affect host-microbe interactions. These RNAs have been suggested as potential host response biomarkers in microbiome-associated disorders, including diabetes and cancer. This article reviews the current understanding of the interplay between gut microbiota and non-coding RNA, including lncRNA, miRNA, and circular RNA. This can lead to a profound understanding of human disease and influence therapy. Furthermore, microbiome engineering as a mainstream strategy for improving human health has been discussed and confirms the hypothesis about a direct cross-talk between microbiome composition and non-coding RNA.
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Affiliation(s)
- Fatemeh Fardi
- Department of Microbiology, Faculty of Biological Sciences, Islamic Azad University, Kish international, Kish, Iran
| | - Leila Bahari Khasraghi
- 15 Khordad Educational Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Negin Shahbakhti
- Department of biology, Faculty of Zoology, University of Razi, Kermanshah, Iran
| | - Amir Salami Naseriyan
- Department of Microbial Biotechnology, Islamic Azad University, Varamin-Pishva Branch, Tabriz, Iran
| | - Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saameh Sanaaee
- Department of New Science, Faculty of Cellular and Molecular biology, Islamic Azad University, Tehran Medical Branch, Tehran, Iran
| | - Iraj Alipourfard
- Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland.
| | - Marzieh Zamany
- Shahid Akbarabadi Clinical Research Development Unit, Iran University of medical Science, Tehran, Iran
| | - Saman Karamipour
- Department of Genetics and Molecular biology, Faculty of Medicine, Iran University of Medical science, Tehran, Iran
| | - Mehdi Jahani
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jamal Majidpoor
- Department of Anatomy, Faculty of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Kambiz Kalhor
- Department of Earth and Planetary Sciences, University of Tennessee, Knoxville, USA.
| | - Mehrdad Talebi
- Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Seyed Mohsen Aghaei-Zarch
- Department of Genetics and Molecular biology, Faculty of Medicine, Iran University of Medical science, Tehran, Iran.
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Palmu J, Börschel CS, Ortega-Alonso A, Markó L, Inouye M, Jousilahti P, Salido RA, Sanders K, Brennan C, Humphrey GC, Sanders JG, Gutmann F, Linz D, Salomaa V, Havulinna AS, Forslund SK, Knight R, Lahti L, Niiranen T, Schnabel RB. Gut microbiome and atrial fibrillation-results from a large population-based study. EBioMedicine 2023; 91:104583. [PMID: 37119735 PMCID: PMC10165189 DOI: 10.1016/j.ebiom.2023.104583] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/26/2023] [Accepted: 04/06/2023] [Indexed: 05/01/2023] Open
Abstract
BACKGROUND Atrial fibrillation (AF) is an important heart rhythm disorder in aging populations. The gut microbiome composition has been previously related to cardiovascular disease risk factors. Whether the gut microbial profile is also associated with the risk of AF remains unknown. METHODS We examined the associations of prevalent and incident AF with gut microbiota in the FINRISK 2002 study, a random population sample of 6763 individuals. We replicated our findings in an independent case-control cohort of 138 individuals in Hamburg, Germany. FINDINGS Multivariable-adjusted regression models revealed that prevalent AF (N = 116) was associated with nine microbial genera. Incident AF (N = 539) over a median follow-up of 15 years was associated with eight microbial genera with false discovery rate (FDR)-corrected P < 0.05. Both prevalent and incident AF were associated with the genera Enorma and Bifidobacterium (FDR-corrected P < 0.001). AF was not significantly associated with bacterial diversity measures. Seventy-five percent of top genera (Enorma, Paraprevotella, Odoribacter, Collinsella, Barnesiella, Alistipes) in Cox regression analyses showed a consistent direction of shifted abundance in an independent AF case-control cohort that was used for replication. INTERPRETATION Our findings establish the basis for the use of microbiome profiles in AF risk prediction. However, extensive research is still warranted before microbiome sequencing can be used for prevention and targeted treatment of AF. FUNDING This study was funded by European Research Council, German Ministry of Research and Education, Academy of Finland, Finnish Medical Foundation, and the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, and the Paavo Nurmi Foundation.
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Affiliation(s)
- Joonatan Palmu
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Department of Internal Medicine, Turku University Hospital and University of Turku, Finland
| | - Christin S Börschel
- Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
| | - Alfredo Ortega-Alonso
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Neuroscience Center, University of Helsinki, Helsinki, Finland; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Lajos Markó
- Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin and the Max-Delbrück Center, Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité - Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
| | - Michael Inouye
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Pekka Jousilahti
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland
| | - Rodolfo A Salido
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Karenina Sanders
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Caitriona Brennan
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Gregory C Humphrey
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Jon G Sanders
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA; Cornell Institute for Host-Microbe Interaction and Disease, Cornell University, Ithaca, NY, USA
| | - Friederike Gutmann
- Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin and the Max-Delbrück Center, Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité - Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
| | - Dominik Linz
- Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, and University of Adelaide, Adelaide, Australia; Department of Cardiology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Veikko Salomaa
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland
| | - Aki S Havulinna
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Institute for Molecular Medicine Finland, FIMM - HiLIFE, Helsinki, Finland
| | - Sofia K Forslund
- Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin and the Max-Delbrück Center, Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité - Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Rob Knight
- Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA
| | - Leo Lahti
- Department of Computing, University of Turku, Turku, Finland
| | - Teemu Niiranen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Department of Internal Medicine, Turku University Hospital and University of Turku, Finland
| | - Renate B Schnabel
- Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
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Piccioni A, Niccolai E, Rozzi G, Spaziani G, Zanza C, Candelli M, Covino M, Gasbarrini A, Franceschi F, Amedei A. Familial Hypercholesterolemia and Acute Coronary Syndromes: The Microbiota-Immunity Axis in the New Diagnostic and Prognostic Frontiers. Pathogens 2023; 12:627. [PMID: 37111513 PMCID: PMC10142551 DOI: 10.3390/pathogens12040627] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 04/29/2023] Open
Abstract
Familial hypercholesterolemia is a common genetic disorder with a propensity towards early onset of atherosclerotic cardiovascular disease (CVD). The main goal of therapy is to reduce the LDL cholesterol and the current treatment generally consists of statin, ezetimibe and PCSK9 inhibitors. Unfortunately, lowering LDL cholesterol may be difficult for many reasons such as the variation of response to statin therapy among the population or the high cost of some therapies (i.e., PCSK9 inhibitors). In addition to conventional therapy, additional strategies may be used. The gut microbiota has been recently considered to play a part in chronic systemic inflammation and hence in CVD. Several studies, though they are still preliminary, consider dysbiosis a risk factor for various CVDs through several mechanisms. In this review, we provide an update of the current literature about the intricate relation between the gut microbiota and the familial hypercholesterolemia.
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Affiliation(s)
- Andrea Piccioni
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy
| | - Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Gloria Rozzi
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy
| | - Giacomo Spaziani
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy
| | - Christian Zanza
- Foundation “Ospedale Alba-Bra Onlus”, Department of Emergency Medicine, Anesthesia and Critical Care Medicine, Michele and Pietro Ferrero Hospital, 12060 Verduno, Italy
| | - Marcello Candelli
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy
| | - Marcello Covino
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy
| | - Antonio Gasbarrini
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy
| | - Francesco Franceschi
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
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Liao J, Zhang Y, Ma C, Wu G, Zhang W. Microbiome-metabolome reveals that the Suxiao Jiuxin pill attenuates acute myocardial infarction associated with fatty acid metabolism. JOURNAL OF ETHNOPHARMACOLOGY 2023; 312:116529. [PMID: 37086873 DOI: 10.1016/j.jep.2023.116529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 05/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Suxiao Jiuxin pill (SJP) is a Chinese medical patent drug on the national essential drug list of China, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been elucidated clearly, especially its relationship with the gut microbiota. AIM OF THE STUDY This study aimed to investigate the cardioprotective effect of SJP against isoproterenol-induced acute myocardial infarction (AMI) by integrating the gut microbiome and metabolome. METHODS A rat model of AMI was generated using isoproterenol. Firstly, the effect of antibiotic (ABX) treatment on the blood absorption and excretion of the main components of SJP were studied. Secondly, 16S rRNA sequencing and untargeted metabolomics were used to discover the improvement of SJP treatment on gut microbiota and host metabolism in AMI rats. Finally, targeted metabolomics was used to verify the effects of SJP treatment on host metabolism in AMI rats. RESULT The results showed that ABX treatment could affect the blood absorption and fecal excretion of the main active components of SJP. At the same time, SJP can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Jeotgalicoccus, Lachnospiraceae, and Blautia) are significantly associated with fatty acids. Untargeted metabolomics also found that SJP could restore the levels of various fatty acid metabolites in serum and cecal contents (p < 0.01, FC > 1.5 and VIP >1). Targeted metabolomics further confirmed that 41, 21, and 39 fatty acids were significantly altered in serum, cecal contents, and heart samples, respectively. Interestingly, these fatty acids belong to the class of eicosanoids, and SJP can significantly downregulate these eicosanoids in AMI rats. CONCLUSION The results of this study suggest that SJP may exert its cardioprotective effects by remodeling the gut microbiota and host fatty acid metabolism.
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Affiliation(s)
- Jingyu Liao
- School of Pharmacy, Guangdong Pharmaceutical University, Guangdong, 510006, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yuhao Zhang
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
| | - Chi Ma
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Gaosong Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Weidong Zhang
- School of Pharmacy, Guangdong Pharmaceutical University, Guangdong, 510006, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
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Tkacheva ON, Klimenko NS, Kashtanova DA, Tyakht AV, Maytesyan LV, Akopyan AA, Koshechkin SI, Strazhesko ID. Gut Microbiome in Post-COVID-19 Patients Is Linked to Immune and Cardiovascular Health Status but Not COVID-19 Severity. Microorganisms 2023; 11:microorganisms11041036. [PMID: 37110459 PMCID: PMC10144658 DOI: 10.3390/microorganisms11041036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 04/08/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
The composition of the gut microbiome stores the imprints of prior infections and other impacts. COVID-19 can cause changes in inflammatory status that persist for a considerable time after infection ends. As the gut microbiome is closely associated with immunity and inflammation, the infection severity might be linked to its community structure dynamics. Using 16S rRNA sequencing of stool samples, we investigated the microbiome three months after the end of the disease/infection or SARS-CoV-2 contact in 178 post-COVID-19 patients and those who contacted SARS-CoV-2 but were not infected. The cohort included 3 groups: asymptomatic subjects (n = 48), subjects who contacted COVID-19 patients with no further infection (n = 46), and severe patients (n = 86). Using a novel compositional statistical algorithm (nearest balance) and the concept of bacterial co-occurrence clusters (coops), we compared microbiome compositions between the groups as well as with multiple categories of clinical parameters including: immunity, cardiovascular parameters and markers of endothelial dysfunction, and blood metabolites. Although a number of clinical indicators varied drastically across the three groups, no differences in microbiome features were identified between them at this follow-up point. However, there were multiple associations between the microbiome features and clinical data. Among the immunity parameters, the relative lymphocyte number was linked to a balance including 14 genera. Cardiovascular parameters were associated with up to four bacterial cooperatives. Intercellular adhesion molecule 1 was linked to a balance including ten genera and one cooperative. Among the blood biochemistry parameters, calcium was the only parameter associated with the microbiome via a balance of 16 genera. Our results suggest comparable recovery of the gut community structure in the post-COVID-19 period, independently of severity or infection status. The multiple identified associations of clinical analysis data with the microbiome provide hypotheses about the participation of specific taxa in regulating immunity and homeostasis of cardiovascular and other body systems in health, as well as their disruption in SARS-CoV-2 infections and other diseases.
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Affiliation(s)
- Olga N Tkacheva
- The "Russian Clinical Research Center for Gerontology" of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, 16 1st Leonova Str., 129226 Moscow, Russia
| | - Natalia S Klimenko
- Atlas Biomed Group-Knomx LLC, Tintagel House, 92 Albert Embankment, Lambeth, London SE1 7TY, UK
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology Russian Academy of Sciences, 34/5 Vavilova Str., 119334 Moscow, Russia
| | - Daria A Kashtanova
- The "Russian Clinical Research Center for Gerontology" of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, 16 1st Leonova Str., 129226 Moscow, Russia
| | - Alexander V Tyakht
- Atlas Biomed Group-Knomx LLC, Tintagel House, 92 Albert Embankment, Lambeth, London SE1 7TY, UK
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology Russian Academy of Sciences, 34/5 Vavilova Str., 119334 Moscow, Russia
| | - Lilit V Maytesyan
- The "Russian Clinical Research Center for Gerontology" of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, 16 1st Leonova Str., 129226 Moscow, Russia
| | - Anna A Akopyan
- The "Russian Clinical Research Center for Gerontology" of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, 16 1st Leonova Str., 129226 Moscow, Russia
| | - Stanislav I Koshechkin
- Atlas Biomed Group-Knomx LLC, Tintagel House, 92 Albert Embankment, Lambeth, London SE1 7TY, UK
| | - Irina D Strazhesko
- The "Russian Clinical Research Center for Gerontology" of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, 16 1st Leonova Str., 129226 Moscow, Russia
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Yntema T, Koonen DPY, Kuipers F. Emerging Roles of Gut Microbial Modulation of Bile Acid Composition in the Etiology of Cardiovascular Diseases. Nutrients 2023; 15:nu15081850. [PMID: 37111068 PMCID: PMC10141989 DOI: 10.3390/nu15081850] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/04/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
Despite advances in preventive measures and treatment options, cardiovascular disease (CVD) remains the number one cause of death globally. Recent research has challenged the traditional risk factor profile and highlights the potential contribution of non-traditional factors in CVD, such as the gut microbiota and its metabolites. Disturbances in the gut microbiota have been repeatedly associated with CVD, including atherosclerosis and hypertension. Mechanistic studies support a causal role of microbiota-derived metabolites in disease development, such as short-chain fatty acids, trimethylamine-N-oxide, and bile acids, with the latter being elaborately discussed in this review. Bile acids represent a class of cholesterol derivatives that is essential for intestinal absorption of lipids and fat-soluble vitamins, plays an important role in cholesterol turnover and, as more recently discovered, acts as a group of signaling molecules that exerts hormonal functions throughout the body. Studies have shown mediating roles of bile acids in the control of lipid metabolism, immunity, and heart function. Consequently, a picture has emerged of bile acids acting as integrators and modulators of cardiometabolic pathways, highlighting their potential as therapeutic targets in CVD. In this review, we provide an overview of alterations in the gut microbiota and bile acid metabolism found in CVD patients, describe the molecular mechanisms through which bile acids may modulate CVD risk, and discuss potential bile-acid-based treatment strategies in relation to CVD.
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Affiliation(s)
- Tess Yntema
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Debby P Y Koonen
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Folkert Kuipers
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
- European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
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Pellegrino A, Coppola G, Santopaolo F, Gasbarrini A, Ponziani FR. Role of Akkermansia in Human Diseases: From Causation to Therapeutic Properties. Nutrients 2023; 15:nu15081815. [PMID: 37111034 PMCID: PMC10142179 DOI: 10.3390/nu15081815] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 04/04/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
The gut microbiota plays a critical role in the modulation of host metabolism and immune response, and its impairment has been implicated in many gastrointestinal and extraintestinal diseases. Current evidence shows the well-documented role of A. muciniphila in maintaining the integrity of the intestinal barrier, modulating the host immune response, and improving several metabolic pathways, making it a key element in the pathogenesis of several human diseases. In this scenario, A. muciniphila is the most promising next-generation probiotic and one of the first microbial species suitable for specific clinical use when compared with traditional probiotics. Further studies are needed to provide more accurate insight into its mechanisms of action and to better elucidate its properties in several major areas, paving the way for a more integrated and personalized therapeutic approach that finally makes the most of our knowledge of the gut microbiota.
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Affiliation(s)
- Antonio Pellegrino
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino, Gemelli IRCCS, 00168 Rome, Italy
| | - Gaetano Coppola
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino, Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino, Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino, Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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40
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Chakaroun RM, Olsson LM, Bäckhed F. The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease. Nat Rev Cardiol 2023; 20:217-235. [PMID: 36241728 DOI: 10.1038/s41569-022-00771-0] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2022] [Indexed: 12/12/2022]
Abstract
Despite milestones in preventive measures and treatment, cardiovascular disease (CVD) remains associated with a high burden of morbidity and mortality. The protracted nature of the development and progression of CVD motivates the identification of early and complementary targets that might explain and alleviate any residual risk in treated patients. The gut microbiota has emerged as a sentinel between our inner milieu and outer environment and relays a modified risk associated with these factors to the host. Accordingly, numerous mechanistic studies in animal models support a causal role of the gut microbiome in CVD via specific microbial or shared microbiota-host metabolites and have identified converging mammalian targets for these signals. Similarly, large-scale cohort studies have repeatedly reported perturbations of the gut microbial community in CVD, supporting the translational potential of targeting this ecological niche, but the move from bench to bedside has not been smooth. In this Review, we provide an overview of the current evidence on the interconnectedness of the gut microbiome and CVD against the noisy backdrop of highly prevalent confounders in advanced CVD, such as increased metabolic burden and polypharmacy. We further aim to conceptualize the molecular mechanisms at the centre of these associations and identify actionable gut microbiome-based targets, while contextualizing the current knowledge within the clinical scenario and emphasizing the limitations of the field that need to be overcome.
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Affiliation(s)
- Rima Mohsen Chakaroun
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
| | - Lisa M Olsson
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Fredrik Bäckhed
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden.
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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41
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Kim Y, Jung S, Park G, Shin H, Heo SC, Kim Y. β-Carotene suppresses cancer cachexia by regulating the adipose tissue metabolism and gut microbiota dysregulation. J Nutr Biochem 2023; 114:109248. [PMID: 36503110 DOI: 10.1016/j.jnutbio.2022.109248] [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: 02/12/2022] [Revised: 10/29/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022]
Abstract
Cancer cachexia is a metabolic disease affecting multiple organs and characterized by loss adipose and muscle tissues. Metabolic dysregulated of adipose tissue has a crucial role in cancer cachexia. β-Carotene (BC) is stored in adipose tissues and increases muscle mass and differentiation. However, its regulatory effects on adipose tissues in cancer cachexia have not been investigated yet. In this study, we found that BC supplementations could inhibit several cancer cachexia-related changes, including decreased carcass-tumor (carcass weight after tumor removal), adipose weights, and muscle weights in CT26-induced cancer cachexia mice. Moreover, BC supplementations suppressed cancer cachexia-induced lipolysis, fat browning, hepatic gluconeogenesis, and systemic inflammation. Altered diversity and composition of gut microbiota in cancer cachexia were restored by the BC supplementations. BC treatments could reverse the down-regulated adipogenesis and dysregulated mitochondrial respiration and glycolysis in adipocytes and colon cancer organoid co-culture systems. Taken together, these results suggest that BC can be a potential therapeutic strategy for cancer cachexia.
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Affiliation(s)
- Yerin Kim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea
| | - Sunil Jung
- Department of Food Science & Biotechnology, and Carbohydrate Bioproduct Research Center, Sejong University, Seoul, Republic of Korea
| | - Gwoncheol Park
- Department of Food Science & Biotechnology, and Carbohydrate Bioproduct Research Center, Sejong University, Seoul, Republic of Korea
| | - Hakdong Shin
- Department of Food Science & Biotechnology, and Carbohydrate Bioproduct Research Center, Sejong University, Seoul, Republic of Korea
| | - Seung Chul Heo
- Department of Surgery, Seoul National University-Seoul Metropolitan Government (SNU-SMG) Boramae Medical Center, Seoul, Republic of Korea
| | - Yuri Kim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea; Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea.
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Crost EH, Coletto E, Bell A, Juge N. Ruminococcus gnavus: friend or foe for human health. FEMS Microbiol Rev 2023; 47:fuad014. [PMID: 37015876 PMCID: PMC10112845 DOI: 10.1093/femsre/fuad014] [Citation(s) in RCA: 136] [Impact Index Per Article: 68.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 02/06/2023] [Accepted: 04/03/2023] [Indexed: 04/06/2023] Open
Abstract
Ruminococcus gnavus was first identified in 1974 as a strict anaerobe in the gut of healthy individuals, and for several decades, its study has been limited to specific enzymes or bacteriocins. With the advent of metagenomics, R. gnavus has been associated both positively and negatively with an increasing number of intestinal and extraintestinal diseases from inflammatory bowel diseases to neurological disorders. This prompted renewed interest in understanding the adaptation mechanisms of R. gnavus to the gut, and the molecular mediators affecting its association with health and disease. From ca. 250 publications citing R. gnavus since 1990, 94% were published in the last 10 years. In this review, we describe the biological characterization of R. gnavus, its occurrence in the infant and adult gut microbiota and the factors influencing its colonization of the gastrointestinal tract; we also discuss the current state of our knowledge on its role in host health and disease. We highlight gaps in knowledge and discuss the hypothesis that differential health outcomes associated with R. gnavus in the gut are strain and niche specific.
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Affiliation(s)
- Emmanuelle H Crost
- Quadram Institute Bioscience, Rosalind Franklin Road, Colney, Norwich NR4 7UQ, United Kingdom
| | - Erika Coletto
- Quadram Institute Bioscience, Rosalind Franklin Road, Colney, Norwich NR4 7UQ, United Kingdom
| | - Andrew Bell
- Quadram Institute Bioscience, Rosalind Franklin Road, Colney, Norwich NR4 7UQ, United Kingdom
| | - Nathalie Juge
- Quadram Institute Bioscience, Rosalind Franklin Road, Colney, Norwich NR4 7UQ, United Kingdom
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Gorbenko AV, Skirdenko YP, Andreev KA, Fedorin MM, Nikolaev NA, Livzan MA. Microbiota and Cardiovascular Diseases: Mechanisms of Influence and Correction Possibilities. RATIONAL PHARMACOTHERAPY IN CARDIOLOGY 2023; 19:58-64. [DOI: 10.20996/1819-6446-2023-01-03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024] Open
Abstract
The term "microbiota" refers to the microbial community occupying a specific habitat with defined physical and chemical properties and forming specific ecological niches. The adult intestinal microbiota is diverse. It mainly consists of bacteria of Bacteroidetes and Firmicutes types. The link between the gut microbiota and cardiovascular disease (CVD) is being actively discussed. Rapid progress in this field is explained by the development of new generation sequencing methods and the use of sterile gut mice in experiments. More and more data are being published about the influence of microbiota on the development and course of hypertension, coronary heart disease (IHD), myocardial hypertrophy, chronic heart failure (CHF) and atrial fibrillation (AF). Diet therapy, antibacterial drugs, pro- and prebiotics are successfully used as tools to correct the structure of the gut microbiota of the macroorganism. Correction of gut microbiota in an experiment on rats with coronary occlusion demonstrates a significant reduction in necrotic area. A study involving patients suffering from CHF reveals a significant reduction in the level of uric acid, highly sensitive C-reactive protein, and creatinine. In addition to structural and laboratory changes in patients with CVD when modifying the microbiota of the gut, also revealed the effect on the course of arterial hypertension. Correction of gut microbiota has a beneficial effect on the course of AF. We assume that further active study of issues of influence and interaction of gut microbiota and macroorganism may in the foreseeable future make significant adjustments in approaches to treatment of such patients.
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Key Stratification of Microbiota Taxa and Metabolites in the Host Metabolic Health-Disease Balance. Int J Mol Sci 2023; 24:ijms24054519. [PMID: 36901949 PMCID: PMC10003303 DOI: 10.3390/ijms24054519] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/21/2023] [Accepted: 02/22/2023] [Indexed: 03/03/2023] Open
Abstract
Human gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health-disease balance. Recent metabolomics and combined metabolome-microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., Faecalibacterium and phosphatidylethanolamine; and the opposite, Escherichia and Phosphatidic Acid, which is converted into the intermediate Cytidine Diphosphate Diacylglycerol-diacylglycerol (CDP-DAG), were overrepresented in metabolic-related disease patients. However, it was not possible to associate most specific microbiota taxa and metabolites according to their increased and decreased profiles analyzed with health or disease. Interestingly, positive association of essential amino acids with the genera Bacteroides were observed in a cluster related to health, and conversely, benzene derivatives and lipidic metabolites were related to the genera Clostridium, Roseburia, Blautia, and Oscillibacter in a disease cluster. More studies are needed to elucidate the microbiota species and their corresponding metabolites that are key in promoting health or disease status. Moreover, we propose that greater attention should be paid to biliary acids and to microbiota-liver cometabolites and its detoxification enzymes and pathways.
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Kadyan S, Park G, Singh P, Arjmandi B, Nagpal R. Prebiotic mechanisms of resistant starches from dietary beans and pulses on gut microbiome and metabolic health in a humanized murine model of aging. Front Nutr 2023; 10:1106463. [PMID: 36824174 PMCID: PMC9941547 DOI: 10.3389/fnut.2023.1106463] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 01/19/2023] [Indexed: 02/10/2023] Open
Abstract
Dietary pulses, being a rich source of fiber and proteins, offer an ideal and inexpensive food choice for older adults to promote gut and metabolic health. However, the prebiotic effects of dietary pulses-derived resistant starches (RS), compared to RS from cereals and tubers, remain relatively underexplored, particularly in context to their gut modulatory potential in old age. We herein investigate the prebiotic effects of pulses-derived RS on the gut microbiome and intestinal health in aged (60-week old) mice colonized with human microbiota. C57B6/J mice were fed for 20 weeks with either a western-style high-fat diet (control; CTL) or CTL diet supplemented (5% w/w) with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin (INU; reference control). We find that the RS supplementation modulates gut microbiome in a sex-dependent manner. For instance, CKP enriched α-diversity only in females, while β-diversity deviated for both sexes. Further, different RS groups exhibited distinct microbiome differences at bacterial phyla and genera levels. Notably, LEN fostered Firmicutes and depleted Proteobacteria abundance, whereas Bacteroidota was promoted by CKP and INU. Genus Dubosiella increased dominantly in males for all groups except PTB, whilst Faecalibaculum decreased in females by CKP and INU groups. Linear discriminant analysis effect size (LEfSe) and correlational analyzes reveal RS-mediated upregulation of key bacterial genera associated with short-chain fatty acids (butyrate) production and suppression of specific pathobionts. Subsequent machine-learning analysis validate decreased abundance of notorious genera, namely, Enterococcus, Odoribacter, Desulfovibrio, Alistipes and Erysipelatoclostridium among RS groups. CKP and LEN groups partly protected males against post-prandial glycemia. Importantly, RS ameliorated high-fat diet-induced gut hyperpermeability and enhanced expression of tight-junction proteins (claudin-1 and claudin-4), which were more pronounced for LEN. In addition, IL10 upregulation was more prominent for LEN, while TNF-α was downregulated by LEN, CKP, and INU. Together, these findings demonstrate that RS supplementation beneficially modulates the gut microbiome with a reduction in gut leakiness and inflammation, indicating their prebiotic potential for functional food and nutritional applications.
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Affiliation(s)
- Saurabh Kadyan
- Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, United States
| | - Gwoncheol Park
- Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, United States
| | - Prashant Singh
- Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, United States
| | - Bahram Arjmandi
- Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, United States
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Jama HA, Rhys-Jones D, Nakai M, Yao CK, Climie RE, Sata Y, Anderson D, Creek DJ, Head GA, Kaye DM, Mackay CR, Muir J, Marques FZ. Prebiotic intervention with HAMSAB in untreated essential hypertensive patients assessed in a phase II randomized trial. NATURE CARDIOVASCULAR RESEARCH 2023; 2:35-43. [PMID: 39196205 DOI: 10.1038/s44161-022-00197-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 11/23/2022] [Indexed: 08/29/2024]
Abstract
Fibers remain undigested until they reach the colon, where some are fermented by gut microbiota, producing metabolites called short-chain fatty acids (SCFAs), such as acetate and butyrate1. SCFAs lower blood pressure in experimental models2-5, but their translational potential is unknown. Here we present the results of a phase II, randomized, placebo-controlled, double-blind cross-over trial (Australian New Zealand Clinical Trials Registry ACTRN12619000916145) using prebiotic acetylated and butyrylated high-amylose maize starch (HAMSAB) supplementation6. Twenty treatment-naive participants with hypertension were randomized to 40 g per day of HAMSAB or placebo, completing each arm for 3 weeks, with a 3-week washout period between them. The primary endpoint was a reduction in ambulatory systolic blood pressure. Secondary endpoints included changes to circulating cytokines, immune markers and gut microbiome modulation. Patients receiving the HAMSAB treatment showed a clinically relevant reduction in 24-hour systolic blood pressure independent of age, sex and body mass index without any adverse effects. HAMSAB increased levels of acetate and butyrate, shifted the microbial ecosystem and expanded the prevalence of SCFA producers. In summary, a prebiotic intervention with HAMSAB could represent a promising option to deliver SCFAs and lower blood pressure in patients with essential hypertension.
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Affiliation(s)
- Hamdi A Jama
- Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, Australia
| | - Dakota Rhys-Jones
- Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, Australia
- Department of Gastroenterology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Michael Nakai
- Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, Australia
| | - Chu K Yao
- Department of Gastroenterology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Rachel E Climie
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
- Sports Cardiology Laboratory, Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Yusuke Sata
- Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Dovile Anderson
- Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia
| | - Darren J Creek
- Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia
| | - Geoffrey A Head
- Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Department of Pharmacology, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - David M Kaye
- Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Department of Cardiology, Alfred Hospital, Melbourne, VIC, Australia
- Central Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Charles R Mackay
- Department of Microbiology, Biomedical Discovery Institute, Faculty of Medicine, Nursing and Health, Monash University, Clayton, VIC, Australia
- School of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Jane Muir
- Department of Gastroenterology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Francine Z Marques
- Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, Australia.
- Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
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Tousoulis D, Guzik T, Padro T, Duncker DJ, De Luca G, Eringa E, Vavlukis M, Antonopoulos AS, Katsimichas T, Cenko E, Djordjevic-Dikic A, Fleming I, Manfrini O, Trifunovic D, Antoniades C, Crea F. Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation. Cardiovasc Res 2022; 118:3171-3182. [PMID: 35420126 PMCID: PMC11023489 DOI: 10.1093/cvr/cvac057] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 01/27/2022] [Accepted: 02/03/2022] [Indexed: 01/25/2023] Open
Abstract
The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions.
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Affiliation(s)
- Dimitris Tousoulis
- 1st Cardiology Department, National and Kapodistrian University of Athens, Vas. Sofias Avenue 114, 11527 Athens, Greece
| | - Tomasz Guzik
- Institute of Cardiovascular Medical Sciences, BHF Glasgow Cardiovascular Research Centre, UK
| | - Teresa Padro
- Sant Pau Institute for Biomedical Research, Barcelona, Spain
| | - Dirk J Duncker
- Department of Cardiology, Thorax Center, Erasmus MC, Rotterdam, the Netherlands
| | - Giuseppe De Luca
- Division of Cardiology, Eastern Piedmont University, Novara, Italy
| | - Etto Eringa
- Institute of Cardiovascular Research, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | | | - Alexios S Antonopoulos
- 1st Cardiology Department, National and Kapodistrian University of Athens, Vas. Sofias Avenue 114, 11527 Athens, Greece
| | - Themistoklis Katsimichas
- 1st Cardiology Department, National and Kapodistrian University of Athens, Vas. Sofias Avenue 114, 11527 Athens, Greece
| | - Edina Cenko
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | | | - Ingrid Fleming
- Centre of Molecular Medicine, Goethe University, Frankfurt, Germany
| | - Olivia Manfrini
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | | | | | - Filippo Crea
- Department of Cardiology and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
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Ghitti E, Rolli E, Crotti E, Borin S. Flavonoids Are Intra- and Inter-Kingdom Modulator Signals. Microorganisms 2022; 10:microorganisms10122479. [PMID: 36557733 PMCID: PMC9781135 DOI: 10.3390/microorganisms10122479] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 12/07/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
Flavonoids are a broad class of secondary metabolites with multifaceted functionalities for plant homeostasis and are involved in facing both biotic and abiotic stresses to sustain plant growth and health. Furthermore, they were discovered as mediators of plant networking with the surrounding environment, showing a surprising ability to perform as signaling compounds for a multitrophic inter-kingdom level of communication that influences the plant host at the phytobiome scale. Flavonoids orchestrate plant-neighboring plant allelopathic interactions, recruit beneficial bacteria and mycorrhizal fungi, counteract pathogen outbreak, influence soil microbiome and affect plant physiology to improve its resilience to fluctuating environmental conditions. This review focuses on the diversified spectrum of flavonoid functions in plants under a variety of stresses in the modulation of plant morphogenesis in response to environmental clues, as well as their role as inter-kingdom signaling molecules with micro- and macroorganisms. Regarding the latter, the review addresses flavonoids as key phytochemicals in the human diet, considering their abundance in fruits and edible plants. Recent evidence highlights their role as nutraceuticals, probiotics and as promising new drugs for the treatment of several pathologies.
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Qian X, Liu A, Liang C, He L, Xu Z, Tang S. Analysis of gut microbiota in patients with acute myocardial infarction by 16S rRNA sequencing. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:1340. [PMID: 36660636 PMCID: PMC9843380 DOI: 10.21037/atm-22-5671] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 12/12/2022] [Indexed: 12/28/2022]
Abstract
Background An increasing number of studies have shown that gut microbiota are associated with human cardiovascular disease, but the characteristics of intestinal flora in patients with acute myocardial infarction (AMI) are still unclear. In this study, we aimed to investigate the difference of intestinal microflora between patients with AMI and healthy people, and to find the effect of percutaneous coronary intervention (PCI) on intestinal microflora. Methods A total of 60 stool samples and 60 peripheral blood samples were collected from 20 previously diagnosed AMI patients and 20 healthy people serving as controls. Gut microbiota communities were analyzed via 16 ribosomal RNA-sequencing (16S rRNA). Gut microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFA), in the blood were detected using stable isotope dilution high-performance liquid chromatography with on line electrospray ionization tandem mass spectrometry (LC/MS/MS). Results The results showed that a distinct pattern of gut microbiota was observed in AMI patients compared to healthy controls. AMI patients had lower microbiological richness but no significant change in diversity. Bacteroidetes and Verrucomicobia showed an upward trend, whereas Proteobacteria showed a downward trend in AMI patients. During a longitudinal study to compare the changes in bacteria before and after treatment, we found routine cardiac admission therapy 1 week after PCI surgery had no effect on the microbial community structure in patients. There were significantly higher levels of plasma TMAO in AMI patients' microbiota than that in the control group. Contrarily, there was no obvious change in SCFA. Conclusions The gut microbiota of patients with AMI differs from that of normal people, and the metabolic products of microflora are more abundant in the plasma of AMI than control cases. Microflora may act on the cardiovascular system through metabolites, and regulation of the microfloral structure may be used in the future treatment of cardiovascular diseases.
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Affiliation(s)
- Xueyi Qian
- Precision Medicine Centre, Yijishan Hospital of Wannan Medical College, Wuhu, China
| | - Ankang Liu
- Department of Cardiology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, China
| | - Chen Liang
- Department of Cardiology, Yijishan Hospital of Wannan Medical College, Wuhu, China
| | - Lianjun He
- Precision Medicine Centre, Yijishan Hospital of Wannan Medical College, Wuhu, China
| | - Zhenyu Xu
- Precision Medicine Centre, Yijishan Hospital of Wannan Medical College, Wuhu, China
| | - Shengxing Tang
- Department of Cardiology, Yijishan Hospital of Wannan Medical College, Wuhu, China
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50
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Li W, Li H, Wang S, Han K, Liu Y, An Z, Wu H, Li J, Song J, Wu W. Regional pattern and signatures of gut microbiota in rural residents with coronary heart disease: A metagenomic analysis. Front Cell Infect Microbiol 2022; 12:1007161. [PMID: 36519129 PMCID: PMC9742380 DOI: 10.3389/fcimb.2022.1007161] [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: 08/02/2022] [Accepted: 10/25/2022] [Indexed: 11/29/2022] Open
Abstract
Coronary heart disease (CHD) is tightly associated with gut microbiota, but microbiota heterogeneity limits the application of microbial biomarkers and personalized interventions demand regional-specific features. The purpose of this study was to comprehensively characterize the regional pattern of gut microbiota in rural residents with CHD and assess the predictive value and clinical correlations of local microbial signatures. We profiled the gut microbiota by shotgun metagenomic sequencing from 19 CHD and 19 healthy residents in rural Xinxiang, China, and tested the physiological parameters. The results indicated that microbial diversity, as well as KEGG orthology (KO) and carbohydrate-active enzymes (CAZymes) functions, deserved no significant disparities between CHD and healthy residents. The relative abundance of Bacteroidetes phylum was significantly lower and unclassified Lachnospiraceae genus, and Eubacterium rectale species were markedly higher in CHD residents compared with the healthy control. Co-occurrence network revealed a more diverse and scattered ecology in CHD residents. LEfSe identified 39 potential biomarkers and butanoate metabolism and glycosyltransferases families were the enhanced KO and CAZymes in CHD residents, respectively. Twenty key signatures were determined by the random forest algorithm and most of them belonged to the Clostridium cluster. These key signatures harbored a superior accuracy of 83.9% to distinguish CHD and healthy residents and, fasting serum insulin, diastolic blood pressure, and body mass index were the top three clinical parameters influencing the gut bacterial community. Furthermore, we also found that low-density lipoprotein and waist circumference had significantly positive correlations with the members of the Clostridium cluster. These findings expand our knowledge in the regional-specific pattern of gut microbiota for rural CHD residents and highlight the non-invasive diagnostic value and clinical correlations of microbial signatures.
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Affiliation(s)
- Wenlong Li
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China,Institute of Infectious Disease Prevention and Control, Zhengzhou Center for Disease Control and Prevention, Zhengzhou, Henan, China
| | - Huijun Li
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Shaolan Wang
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Keyang Han
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Yuan Liu
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Zhen An
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Hui Wu
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Juan Li
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Jie Song
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
| | - Weidong Wu
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China,*Correspondence: Weidong Wu,
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