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Dongre DS, Saha UB, Saroj SD. Exploring the role of gut microbiota in antibiotic resistance and prevention. Ann Med 2025; 57:2478317. [PMID: 40096354 PMCID: PMC11915737 DOI: 10.1080/07853890.2025.2478317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/24/2025] [Accepted: 02/27/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND/INTRODUCTION Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials. MAIN BODY This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment. DISCUSSION Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.
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Affiliation(s)
- Devyani S. Dongre
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra, India
| | - Ujjayni B. Saha
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra, India
| | - Sunil D. Saroj
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra, India
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2
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Gustafson KL, Rodriguez TR, McAdams ZL, Coghill LM, Ericsson AC, Franklin CL. Failure of colonization following gut microbiota transfer exacerbates DSS-induced colitis. Gut Microbes 2025; 17:2447815. [PMID: 39812347 PMCID: PMC11740679 DOI: 10.1080/19490976.2024.2447815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 12/13/2024] [Accepted: 12/23/2024] [Indexed: 01/16/2025] Open
Abstract
To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.
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Affiliation(s)
- Kevin L. Gustafson
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
- Comparative Medicine Program, University of Missouri, Columbia, MO, USA
- MU Mutant Mouse Resource and Research Center, University of Missouri, Columbia, MO, USA
| | - Trevor R. Rodriguez
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
- Comparative Medicine Program, University of Missouri, Columbia, MO, USA
| | - Zachary L. McAdams
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
- MU Mutant Mouse Resource and Research Center, University of Missouri, Columbia, MO, USA
- Molecular Pathogenesis and Therapeutics Program, University of Missouri, Columbia, MO, USA
| | - Lyndon M. Coghill
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
- University of Missouri Bioinformatics and Analytics Core, University of Missouri, Columbia, MO, USA
| | - Aaron C. Ericsson
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
- Comparative Medicine Program, University of Missouri, Columbia, MO, USA
- MU Mutant Mouse Resource and Research Center, University of Missouri, Columbia, MO, USA
- University of Missouri College of Veterinary Medicine, Columbia, MO, USA
- University of Missouri Metagenomics Center, Columbia, MO, USA
| | - Craig L. Franklin
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
- Comparative Medicine Program, University of Missouri, Columbia, MO, USA
- MU Mutant Mouse Resource and Research Center, University of Missouri, Columbia, MO, USA
- University of Missouri College of Veterinary Medicine, Columbia, MO, USA
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3
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Chen LR, Zhou SS, Yang JX, Liu XQ. Effect of hypoxia on the mucus system and intragastric microecology in the gastrointestinal tract. Microb Pathog 2025; 205:107615. [PMID: 40355054 DOI: 10.1016/j.micpath.2025.107615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 04/03/2025] [Accepted: 04/17/2025] [Indexed: 05/14/2025]
Abstract
Digestive diseases have a high incidence worldwide, with various geographic, age, and gender factors influencing the occurrence and development of the diseases. The main etiologic factors involve genetics, environment, lifestyle, and dietary habits. In a low-oxygen environment, however, the body's tissue cells activate hypoxia-inducible factor (HIF), which produces different inflammatory mediators. Hypoxia impacts health at the molecular level by modulating cellular stress responses, metabolic pathways, and immune functions. It also alters gene expression and cellular behavior, thereby affecting gastrointestinal function. Under normal physiological conditions, the gastrointestinal mucus system serves as a crucial protective barrier, defending against mechanical injury, pathogenic invasion, and exposure to harmful chemicals. The integrity and functionality of this barrier are dependent on the synthesis and regulation of mucins and mucus, which are influenced by multiple factors. Additionally, the composition and diversity of the gastric microbiota are shaped by factors such as Helicobacter pylori infection, diet, and lifestyle. A balanced gastric microbiota supports gastrointestinal health and fortifies the mucus barrier. However, hypoxia can disrupt this equilibrium, leading to inflammation, alterations in the mucus layer, and destabilization of the gastric microbiota. Understanding the interplay between hypoxia, the mucus system, and the gastric microbiota is essential for identifying novel therapeutic strategies. Future research should elucidate the mechanisms through which hypoxia influences these systems and develop interventions to mitigate its adverse effects on gastrointestinal health. We examined the impact of hypoxia on the gastrointestinal mucus system and gastric microbiota, highlighting its implications for human health and potential therapeutic approaches.
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Affiliation(s)
- Li Rong Chen
- Qinghai University, Xining, 810001, PR China; Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China
| | - Si Si Zhou
- Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China; Department of Gastroenterology, Qinghai Provincial People's Hospital, Xining, 810001, PR China; Qinghai Provincial Clinical Medical Research Center for Digestive Diseases, Xining, 810001, PR China.
| | - Ji Xiang Yang
- Qinghai University, Xining, 810001, PR China; Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China
| | - Xiao Qian Liu
- Qinghai University, Xining, 810001, PR China; Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China
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4
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Kulkarni H, Gaikwad AB. The mitochondria-gut microbiota crosstalk - A novel frontier in cardiovascular diseases. Eur J Pharmacol 2025; 998:177562. [PMID: 40157703 DOI: 10.1016/j.ejphar.2025.177562] [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: 02/12/2025] [Revised: 03/06/2025] [Accepted: 03/26/2025] [Indexed: 04/01/2025]
Abstract
Cardiovascular diseases (CVDs), including hypertension, atherosclerosis, and cardiomyopathy among others, remain the leading cause of global morbidity and mortality. Despite advances in treatment, the complex pathophysiology of CVDs necessitates innovative approaches to improve patient outcomes. Recent research has uncovered a dynamic interplay between mitochondria and gut microbiota, fundamentally altering our understanding of cardiovascular health. However, while existing studies have primarily focused on individual components of this axis, this review examines the bidirectional communication between these biological systems and their collective impact on cardiovascular health. Mitochondria, serving as cellular powerhouses, are crucial for maintaining cardiovascular homeostasis through oxidative phosphorylation (OXPHOS), calcium regulation, and redox balance. Simultaneously, the gut microbiota influences cardiovascular function through metabolite production, barrier integrity maintenance, and immune system modulation. The mitochondria-gut microbiota axis operates through various molecular mechanisms, including microbial metabolites such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFA), and secondary bile acids, which directly influence mitochondrial function. Conversely, mitochondrial stress signals and damage-associated molecular patterns (DAMPs) affect gut microbial communities and barrier function. Key signalling pathways, including AMP-activated protein kinase (AMPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the silent information regulator 1-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1-PGC-1α) axis, integrate these interactions, highlighting their role in CVD pathogenesis. Understanding these interactions has revealed promising therapeutic targets, suggesting new therapies aimed at both mitochondrial function and gut microbiota composition. Thus, this review provides a comprehensive framework for leveraging the mitochondria-gut microbiota axis in providing newer therapeutics for CVDs by targeting the AMPK/SIRT-1/PGC-1α/NF-κB signalling.
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Affiliation(s)
- Hrushikesh Kulkarni
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333031, India
| | - Anil Bhanudas Gaikwad
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333031, India.
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Mahmoud AA, Wang X, Liao X, Zhang S, Ding T, Ahn J. Impact of prophages on gut microbiota and disease associations. Microb Pathog 2025; 204:107642. [PMID: 40300731 DOI: 10.1016/j.micpath.2025.107642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 04/01/2025] [Accepted: 04/26/2025] [Indexed: 05/01/2025]
Abstract
The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.
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Affiliation(s)
- Aminu Abdullahi Mahmoud
- Future Food Laboratory, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, Zhejiang 314100, China; Department of Food Science and Nutrition, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Xiaoyu Wang
- Future Food Laboratory, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, Zhejiang 314100, China; Department of Food Science and Nutrition, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Xinyu Liao
- Future Food Laboratory, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, Zhejiang 314100, China
| | - Song Zhang
- Department of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
| | - Tian Ding
- Future Food Laboratory, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, Zhejiang 314100, China; Department of Food Science and Nutrition, Zhejiang University, Hangzhou, Zhejiang 310058, China.
| | - Juhee Ahn
- Future Food Laboratory, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, Zhejiang 314100, China; Department of Food Science and Nutrition, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
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6
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Cheng B, Feng H, Li C, Jia F, Zhang X. The mutual effect of dietary fiber and polyphenol on gut microbiota: Implications for the metabolic and microbial modulation and associated health benefits. Carbohydr Polym 2025; 358:123541. [PMID: 40383597 DOI: 10.1016/j.carbpol.2025.123541] [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: 01/17/2025] [Revised: 03/16/2025] [Accepted: 03/25/2025] [Indexed: 05/20/2025]
Abstract
Gut microbiota plays a critical role in maintaining human health by regulating digestion, metabolism, and immune function. Emerging research highlights the potential of dietary interventions, particularly dietary fiber (DF) and polyphenols, in modulating gut microbiota composition and function. DF serves as a fermentable substrate for beneficial gut bacteria, promoting the production of short-chain fatty acids (SCFAs). Polyphenols, a diverse group of bioactive compounds selectively modulate microbial populations and contribute to the production of bioactive metabolites with host health benefits. Importantly, the interplay between DF and polyphenols creates a synergistic effect within the gut microbiome, shaping microbial diversity, enhancing SCFAs production, and strengthening gut barrier function, which together support metabolic and immune homeostasis. This review systematically explores the synergistic effects of DF-polyphenol combinations on gut microbiota modulation, microbial metabolites, and their implications for overall health. The combined effects of DF and polyphenols hold promise for targeted nutritional strategies in preventing metabolic disorders and improving gut health. Moreover, the extent of these benefits is influenced by the structural characteristics of DF, the source and dosage of polyphenols, and individual gut microbiota composition. Further research is warranted to optimize DF-polyphenol interactions and facilitate their applications in personalized nutrition and functional food development.
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Affiliation(s)
- Bo Cheng
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Hongyan Feng
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Cheng Li
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin 999077, Hong Kong, China
| | - Fei Jia
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, Shandong Province, China
| | - Xiaowei Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
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7
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Cheng MC, Chen HM, Chang TY, Chen MC, Bai BJ, Chao CH, Hsieh WY, Lin YT, Ni CK, Lu MK, Liu HK, Lee SS, Chang CC. Acetylated glucomanno-oligosaccharides from human gut microbial degradation of Dendrobium polysaccharides: production and effects on anti-hyperglycemia-related factors. CARBOHYDRATE POLYMER TECHNOLOGIES AND APPLICATIONS 2025; 10:100808. [DOI: 10.1016/j.carpta.2025.100808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2025] Open
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8
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Støy S, Schnabl B. Role of Intestinal Microbiome in Potentiating Inflammation and Predicting Outcomes in Alcohol-Associated Cirrhosis. Gastroenterol Clin North Am 2025; 54:453-467. [PMID: 40348498 PMCID: PMC12066832 DOI: 10.1016/j.gtc.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
In patients with alcohol-associated cirrhosis, the intestinal microbiome composition is disturbed with a loss of beneficial functions and an increase in pathobionts. These changes are associated with disease severity and decompensation, due in part to the exacerbation of liver inflammation by an altered microbiome. Microbes or their antigens may translocate to the liver to potentiate the activation of immune cells and thereby contribute to inflammatory injury. Moreover, microbes may aggravate liver disease through the production of toxins or metabolites, via the effects on bile acids or the intestinal immune system.
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Affiliation(s)
- Sidsel Støy
- Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
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9
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Hosseini FS, Behrouzi A, Shafaie E, Sharifi F, Ejtahed HS. Assessment of gut microbiota in the elderly with sarcopenic obesity: a case-control study. J Diabetes Metab Disord 2025; 24:83. [PMID: 40093788 PMCID: PMC11909374 DOI: 10.1007/s40200-025-01584-x] [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: 12/09/2024] [Accepted: 02/04/2025] [Indexed: 03/19/2025]
Abstract
Objectives Sarcopenic obesity is a multifactorial disorder commonly found in elderly individuals. One contributing factor is gut microbiota dysbiosis. This study compared the abundance of certain bacteria in elderly individuals with obesity and sarcopenic obesity. Methods The study included 50 elderly individuals over 65 with a body mass index (BMI) of over 30 kg/m², both sexes. Participants were divided into two groups, each with 25 individuals, based on the diagnosis of sarcopenia using the EWGSOP2 criteria. Individuals with underlying diseases, those using antibiotics, and those with a history of gastrointestinal surgery were excluded. Stool samples were stored at -80 °C, and DNA was extracted using standard kits. Bacterial DNA sample quality was assessed using a Nanodrop device. Bacterial frequency was measured using qPCR. The log cfu for each bacteria was calculated and compared in both groups using an independent t-test. Spearman measured the correlation between bacterial genera and physical performance in SPSS 26. Results The case group had a significantly higher average age (70.96) than the control group (68.32). The average BMI was the same in both groups. The frequency of Escherichia (p-value = 0.046) and Bifidobacterium (p-value = 0.017) was significantly higher in the case group. There was no significant difference in the frequency of Lactobacillus and Akkermansia. Conclusion The study uncovered substantial differences in gut microbiota composition between elderly individuals experiencing sarcopenic obesity and those with obesity alone. The findings suggest that dysbiosis, characterized by an excessive presence of Bifidobacterium, Escherichia, and Akkermansia, may be associated with sarcopenic obesity. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-025-01584-x.
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Affiliation(s)
| | - Ava Behrouzi
- Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
| | - Ebrahim Shafaie
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Farshad Sharifi
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Bolsega S, Bleich A, Dorsch M, Basic M. Biological adaptation to a germ-free environment should not be mistaken as a burden for animals. Lab Anim 2025; 59:384-389. [PMID: 39817369 PMCID: PMC12120197 DOI: 10.1177/00236772241287847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/09/2024] [Indexed: 01/18/2025]
Affiliation(s)
- Silvia Bolsega
- Institute for Laboratory Animal Science, Hannover Medical School, Germany
| | - André Bleich
- Institute for Laboratory Animal Science, Hannover Medical School, Germany
| | - Martina Dorsch
- Institute for Laboratory Animal Science, Hannover Medical School, Germany
| | - Marijana Basic
- Institute for Laboratory Animal Science, Hannover Medical School, Germany
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Nishinarita Y, Miyoshi J, Kuronuma S, Wada H, Oguri N, Hibi N, Takeuchi O, Akimoto Y, Lee STM, Matsuura M, Kobayashi T, Hibi T, Hisamatsu T. Characteristic gene expression profile of intestinal mucosa early in life promotes bacterial colonization leading to healthy development of the intestinal environment. Sci Rep 2025; 15:18437. [PMID: 40419682 DOI: 10.1038/s41598-025-03661-w] [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: 04/16/2024] [Accepted: 05/21/2025] [Indexed: 05/28/2025] Open
Abstract
The gut microbiome early in life plays a crucial role in development of the host and affects health throughout life. The definition of a healthy microbiome early in life has not been established, and the underlying mechanism of how a young host selects appropriate microbes for colonization remains unclear. Understanding the mechanism may provide insights into novel preventive and therapeutic strategies by correcting dysbiosis early in life. We employed germ-free mice early in life (4 weeks of age) and later in life (10 weeks of age) for fecal microbiota transfer (FMT) from specific pathogen-free mice. We performed age-unmatched FMT between recipients early in life and donors early or later in life, in addition to common age-matched FMT. Age-matched FMT resulted in significantly different bacterial compositions between recipients early vs. later in life. When the gut microbiome from donors early or later in life was transferred to recipients early in life, bacterial compositions of recipients from donors later in life were similar to those of recipients from donors early in life. This finding suggests that the host early in life has mechanisms to select microbes appropriate for age from the exposed microbiome. We hypothesized that the age-specific intestinal environment promotes age-appropriate intestinal microbiome colonization and examined gene expression in the intestinal mucosa of germ-free mice. We observed that gene expression profiles were different between early vs. later in life. Correlation analysis demonstrated that genera Lachnospiraceae NK4A136 group and Roseburia were positively correlated to genes expressed predominantly early in life, but negatively with genes expressed predominantly later in life. We confirmed that the relative abundance of these genera was significantly higher in specific pathogen-free mice early in life compared with mice later in life. The characteristic gene expression of the intestinal mucosa early in life might play roles in selecting specific bacteria in the intestinal microbiome early in life.
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Affiliation(s)
- Yuu Nishinarita
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-Shi, Tokyo, 181-8611, Japan
| | - Jun Miyoshi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-Shi, Tokyo, 181-8611, Japan.
| | - Satoshi Kuronuma
- Department of Research, BioMedical Laboratory, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Haruka Wada
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-Shi, Tokyo, 181-8611, Japan
| | - Noriaki Oguri
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-Shi, Tokyo, 181-8611, Japan
| | - Noritaka Hibi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-Shi, Tokyo, 181-8611, Japan
| | - Osamu Takeuchi
- Department of Research, BioMedical Laboratory, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Yoshihiro Akimoto
- Department of Microscopic Anatomy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611, Japan
| | - Sonny T M Lee
- Division of Biology, Kansas State University, 136 Ackert Hall, 1717 Claflin Rd, Manhattan, KS, 66506, USA
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-Shi, Tokyo, 181-8611, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-Shi, Tokyo, 181-8611, Japan.
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Li D, Zhang DY, Chen SJ, Lv YT, Huang SM, Chen C, Zeng F, Chen RX, Zhang XD, Xiong JX, Chen FD, Jiang YH, Chen Z, Mo CY, Chen JJ, Zhu XL, Zhang LJ, Bai FH. Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts. Front Cell Infect Microbiol 2025; 15:1565887. [PMID: 40491436 PMCID: PMC12146308 DOI: 10.3389/fcimb.2025.1565887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 04/17/2025] [Indexed: 06/11/2025] Open
Abstract
Objective COVID-19 has had a profound impact on public health globally. However, most studies have focused on patients with long COVID or those in the acute phase of infection, with limited research on the health of individuals who have recovered from mild COVID-19. This study investigates the long-term changes in bacterial and fungal communities in individuals recovering from mild COVID-19 and their clinical relevance. Methods Healthy individuals from Hainan Province were enrolled before the COVID-19 outbreak, along with individuals recovering from COVID-19 at 3 months and 6 months post-recovery. Stool, blood samples, and metadata were collected. Metagenomic sequencing and Internal Transcribed Spacer (ITS) analysis characterized bacterial and fungal communities, while bacterial-fungal co-occurrence networks were constructed. A random forest model evaluated the predictive capacity of key taxa. Results The gut microbiota of COVID-19 recoverees differed significantly from that of healthy individuals. At 3 months post-recovery, probiotics (e.g., Blautia massiliensis and Kluyveromyces spp.) were enriched, linked to improved metabolism, while at 6 months, partial recovery of probiotics (e.g., Acidaminococcus massiliensis and Asterotremella spp.) was observed alongside persistent pathogens (e.g., Streptococcus equinus and Gibberella spp.). Dynamic changes were observed, with Acidaminococcus massiliensis enriched at both baseline and 6 months but absent at 3 months. Co-occurrence network analysis revealed synergies between bacterial (Rothia spp.) and fungal (Coprinopsis spp.) taxa, suggesting their potential roles in gut restoration. The bacterial random forest model (10 taxa) outperformed the fungal model (8 taxa) in predicting recovery status (AUC = 0.99 vs. 0.80). Conclusion These findings highlight the significant long-term impacts of mild COVID-19 recovery on gut microbiota, with key taxa influencing metabolism and immune regulation, supporting microbiome-based strategies for recovery management.
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Affiliation(s)
- Da Li
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Da-Ya Zhang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Shi-Ju Chen
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Yan-Ting Lv
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Shi-Mei Huang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Chen Chen
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Fan Zeng
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Run-Xiang Chen
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Xiao-Dong Zhang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
| | - Jian-Xin Xiong
- Department of Gastroenterology, Hainan Second People’s Hospital, Wuzhishan, China
| | - Fa-Di Chen
- Department of Gastroenterology, Wuzhishan Center for Disease Control and Prevention, Wuzhishan, China
| | - Yue-Hong Jiang
- Department of Gastroenterology, The Second People ‘s Hospital of Ledong Li Autonomous County, Ledong Li Autonomous County, China
| | - Zhai Chen
- Department of Gastroenterology, Dongfang People’s Hospital, Dongfang, China
| | - Cui-Yi Mo
- Department of Gastroenterology, Qionghai People’s Hospital, Qionghai, China
| | - Jia-Jia Chen
- Department of Gastroenterology, Qionghai People’s Hospital, Qionghai, China
| | - Xu-Li Zhu
- Departmenrt of Internal Medicine, Otog Front Banner People ‘s Hospital, Otog Front Banner, China
| | - Li-Jun Zhang
- Health Management Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Fei-Hu Bai
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, China
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13
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Yang B, Rutkowski N, Ruta A, Gray-Gaillard E, Maestas DR, Kelly SH, Krishnan K, Wu X, Wu S, Chen A, Mejías JC, Hooks JST, Vanderzee I, Mensah P, Celik N, Eric M, Abraham P, Tam A, Housseau F, Pardoll DM, Sears CL, Elisseeff JH. Murine gut microbiota dysbiosis via enteric infection modulates the foreign body response to a distal biomaterial implant. Proc Natl Acad Sci U S A 2025; 122:e2422169122. [PMID: 40354538 PMCID: PMC12107164 DOI: 10.1073/pnas.2422169122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 04/09/2025] [Indexed: 05/14/2025] Open
Abstract
The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response and fibrosis is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via infection with the pathogenic bacterial species enterotoxigenic Bacteroides fragilis (ETBF) and implanted particulate material (mean particle size <600 μm) of the synthetic polymer polycaprolactone (PCL) into a distal muscle injury. ETBF infection in mice led to increased neutrophil and γδ T cell infiltration into the PCL implant site. ETBF infection alone promoted systemic inflammation, increased levels of neutrophils in lymphoid tissues, and altered skeletal muscle gene expression. At the PCL implant site, we found significant changes in the transcriptome of sorted stromal cells between infected and control mice, including differences related to ECM components such as proteoglycans and glycosaminoglycans. However, we did not observe ETBF-induced differences in fibrosis levels. These results demonstrate the ability of the gut microbiota to mediate long-distance effects such as immune and stromal responses to a distal biomaterial implant.
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Affiliation(s)
- Brenda Yang
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Natalie Rutkowski
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Anna Ruta
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Elise Gray-Gaillard
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - David R. Maestas
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Sean H. Kelly
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Kavita Krishnan
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Xinqun Wu
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD21287
| | - Shaoguang Wu
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD21287
| | - Allen Chen
- Department of Biomedical Engineering, Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD21218
| | - Joscelyn C. Mejías
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Joshua S. T. Hooks
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Isabel Vanderzee
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Patricia Mensah
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Nazmiye Celik
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Marie Eric
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Peter Abraham
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
| | - Ada Tam
- Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD21287
- Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD21287
| | - Franck Housseau
- Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD21287
- Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD21287
| | - Drew M. Pardoll
- Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD21287
- Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD21287
| | - Cynthia L. Sears
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD21287
- Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD21287
- Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD21287
- Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD21287
| | - Jennifer H. Elisseeff
- Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD21231
- Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD21287
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14
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Jaworska K, Kuś M, Ufnal M. TMAO and diabetes: from the gut feeling to the heart of the problem. Nutr Diabetes 2025; 15:21. [PMID: 40393987 DOI: 10.1038/s41387-025-00377-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 04/30/2025] [Accepted: 05/06/2025] [Indexed: 05/22/2025] Open
Abstract
Elevated plasma levels of trimethylamine N-oxide (TMAO)-a compound derived from diet and the gut microbiome-have been widely studied for their association with diabetes risk and their potential role in disease pathophysiology and complications. However, clinical studies, both prospective and retrospective, have yielded conflicting results. For example, elevated levels of TMAO are frequently linked to an increased risk of cardiovascular and renal complications in individuals with diabetes. However, the robustness and independence of these associations differ across study populations and are influenced by the degree of adjustment for confounding risk factors. Considering insulin's regulatory effect on FMO3 activity in liver cells, TMAO may serve as a marker of hepatic insulin resistance, which could partially explain its association with diabetes risk. The role of TMAO in diabetes pathology remains controversial; while some studies emphasize its detrimental impact on insulin sensitivity and the progression of diabetes-related complications, others suggest potential protective effects. Investigating the largely unexplored role of TMAO's precursor, trimethylamine, may help elucidate these discrepancies. This review consolidates clinical and experimental findings to clarify TMAO's complex mechanistic contributions to diabetes pathology.
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Affiliation(s)
- Kinga Jaworska
- Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
| | - Monika Kuś
- Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
| | - Marcin Ufnal
- Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
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15
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Cheng G, Kong W, Lin R, Jiang Z, Wang X, Qin X, Shi Y, Yang P, Chen X, Xia L, Xu Z. Multi-omics analysis reveals that Bacillus spp. enhance mucosal antiviral immunity in teleost fish by mediating diglyceride production through lipid metabolism. MICROBIOME 2025; 13:123. [PMID: 40380241 PMCID: PMC12083065 DOI: 10.1186/s40168-025-02124-8] [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] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 04/27/2025] [Indexed: 05/19/2025]
Abstract
BACKGROUND Symbiotic microbiota in vertebrates play critical roles in establishing and enhancing host resistance to pathogenic infections as well as maintaining host homeostasis. The interactions and mechanisms of commensal microbiota-mediated mucosal immune systems have been extensively studied in mammals and, to a lesser extent, in birds. However, despite several studies emphasizing the role of mucosal microbiota in controlling pathogen infections in teleost fish, limited knowledge exists regarding the core microbiota and the mechanisms by which they contribute to resistance against viral infections. RESULTS Our findings suggest that viral infections shape clinical manifestations of varying severity in infected fish. An increased abundance of Bacillus spp. in the mild phenotype indicates its crucial role in influencing fish immunity during viral infections. To confirm that Bacillus spp. act as a core contributor against viral infection in fish, we isolated a representative strain of Bacillus spp. from largemouth bass (Micropterus salmoides), which was identified as Bacillus velezensis (Bv), and subsequently conducted feeding trials. Our study demonstrated that dietary supplementation with Bv significantly reduced mortality from largemouth bass virus (LMBV) infection in bass by enhancing host immunity and metabolism as well as by regulating the microbial community. Furthermore, multi-omics analysis elucidated the mechanism by which Bacillus spp. confer resistance to viral infections by regulating the production of diglyceride (DG) during lipid metabolism. CONCLUSIONS Our study provides the first evidence that Bacillus spp. are a core microbiota for combating viral infections in teleost fish, shedding light on the conserved functions of probiotics as a core microbiota in regulating microbial homeostasis and mucosal immunity across the vertebrate lineage.
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Affiliation(s)
- Gaofeng Cheng
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Weiguang Kong
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Ruiqi Lin
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Zhihao Jiang
- Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China
| | - Xinyou Wang
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Xueying Qin
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Yong Shi
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Peng Yang
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Xiaoyun Chen
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Lu Xia
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Zhen Xu
- State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
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16
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Hanna A, Abbas H, Yassine F, AlBush A, Bilen M. Systematic review of gut microbiota composition, metabolic alterations, and the effects of treatments on PCOS and gut microbiota across human and animal studies. Front Microbiol 2025; 16:1549499. [PMID: 40438215 PMCID: PMC12116390 DOI: 10.3389/fmicb.2025.1549499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 04/15/2025] [Indexed: 06/01/2025] Open
Abstract
Introduction Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting around 12% of women globally, associated with infertility and various comorbidities. Emerging evidence suggests a crucial role of gut microbiota in PCOS pathophysiology, prompting research to investigate alterations in gut microbial composition in patients with PCOS. Methods This systematic review aims to analyze human and animal studies that compare gut microbiota composition, gut-derived metabolites, and treatment interventions in PCOS patients versus healthy controls. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, yielding studies examining gut microbiota, metabolomic shifts, and treatment responses in PCOS models and human populations. Results Our analysis revealed decreases in alpha diversity in PCOS patients, with more pronounced changes in beta diversity in animal models. Specific bacterial taxa, such as Bacteroides vulgatus, Escherichia-Shigella and Lactobacillus, showed implication in PCOS pathogenesis, suggesting potential microbial markers. Furthermore, discrepancies between human and animal studies show the need for humanized mouse models to bridge this gap. Interventions like probiotics and fecal microbiota transplantation (FMT) showed varying levels of efficacy, with FMT emerging as a more promising but invasive option, offering live bacteriotherapy as a potential therapeutic alternative. Alterations in gut-derived metabolites, including short-chain fatty acids and bile acids, highlighted the multifaceted nature of PCOS, with implications extending to metabolic, hormonal, and gut-brain axis disruptions. Discussion In conclusion, PCOS exhibits complex interactions between gut microbiota and metabolic pathways, necessitating further research with standardized methods and larger sample sizes to elucidate the microbiome's role in PCOS.
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Affiliation(s)
- Aya Hanna
- Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Hassan Abbas
- Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Fayez Yassine
- Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Alia AlBush
- Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Melhem Bilen
- Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Centre for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon
- World Health Organization (WHO) Collaborating Centre for Reference and Research on Bacterial Pathogens, Beirut, Lebanon
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17
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Yu Z, Zhao Z, Pan Y, Zhao L, Xiao Y, Yue D, Yu Y, Jiang J, Zhou Z. Abnormal gill color of Manila clam Ruditapes philippinarum due to the unhealthy gut mcirobiota and the role of gut-gill axis. FISH & SHELLFISH IMMUNOLOGY 2025; 163:110404. [PMID: 40350106 DOI: 10.1016/j.fsi.2025.110404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 05/07/2025] [Accepted: 05/08/2025] [Indexed: 05/14/2025]
Abstract
The Manila clam (Ruditapes philippinarum) is an ecologically and economically important species. Recently, a novel disease of Manila clam with abnormal gill colour has emerged, leading to growth inhibition and death in severe cases. In this study, a multi-omics approach was used to investigate the underlying mechanisms of abnormal gill colour in Manila clam and its association with gut microbiota. High-throughput sequencing revealed a reduction in the uniformity of gut microbiota in diseased clams, with increased abundance of Pseudomonas and Pseudoaltermonas. Network and null model analyses revealed a decline in microbiota stability and a shift toward deterministic assembly in diseased clams. Transcriptomic analysis revealed different gene expression profiles in the gills of healthy and diseased Manila clams, including down-regulation of several immune-related genes such as genes encoding heat shock proteins and involved in Toll and Imd signalling pathways. A total of 38 specialists were identified in the gut microbiota of diseased Manila clams based on their specificity and occupancy. Four of them (two Psychrobacter, one Pseudoaltermonas and one Halomonas) were closely correlated with the expression of gill genes associated with abnormal gill colour. In addition, a gene encoding a major vault protein was identified as the keystone of abnormal gill colour through the network of host genes and their gut microbiota. This study revealed the substantial variation in gut microbiota and gill gene expression in Manila clam with abnormal gill colour and provided insights into the complex host-microbiota interactions involved in disease development.
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Affiliation(s)
- Zuoan Yu
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Zelong Zhao
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Yongjia Pan
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Liang Zhao
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Yao Xiao
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Dongmei Yue
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Yuanfu Yu
- Dalian Baijuxin Marine Ranch Co., Ltd, Dalian, Liaoning 116500, RP China
| | - Jingwei Jiang
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China.
| | - Zunchun Zhou
- Ministry of Agriculture and Rural Affairs Key Lab of Protection and Utilization of Aquatic Germplasm Resource, Liaoning Key Lab of Germplasm Improvement and Fine Seed Breeding of Marine Aquatic Animals, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China.
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18
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Sharif-Askari EA, Atoui KM, Mteyrek AK, Fawaz LM. Probiotics and mediterranean diet for breast cancer management and prevention? Cell Stress 2025; 9:1-15. [PMID: 40417456 PMCID: PMC12096334 DOI: 10.15698/cst2025.05.303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2025] [Revised: 01/30/2025] [Accepted: 03/25/2025] [Indexed: 05/27/2025] Open
Abstract
The human gut microbiota, a diverse community of beneficial normal flora microorganisms, significantly influences physiological function and the immune response. Various microbiota strains have shown promise in supporting clinical treatment of chronic diseases, including cancer, by potentially providing antioxidative and anti-tumorigenic effects in both in vivo and in vitro studies. Breast cancer, which ranks amongst the top five cancer types common worldwide and particularly in Mediterranean countries, has been showing high incidence and prevalence. In breast cancer, microbiota composition, hormonal dynamics, and dietary choices are believed to play significant roles. Hence, the Mediterranean diet, known for its microbiota-friendly features, emerges as a potential protective factor against breast cancer development, highlighting the potential for personalized dietary strategies in cancer prevention. This comprehensive review highlights the emerging mechanisms by which probiotics support our immune system during different physiological activities. It also discusses their potential role, along with nutrition intervention, in improving essential clinical treatment outcomes in breast cancer patients and survivors, suggesting potential supportive strategies that go hand in hand with clinical strategies. Unfortunately, very little research addresses the possible clinical implications of probiotics and dietary habits on breast cancer, despite the promising results, calling for further studies and actions.
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Affiliation(s)
- Ehssan A. Sharif-Askari
- Biomedical Science Department, School of Arts & Sciences, Lebanese International University, Tyre, Lebanon
| | - Khadija M. Atoui
- Biomedical Science Department, School of Arts & Sciences, Lebanese International University, Tyre, Lebanon
| | - Ali K. Mteyrek
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Tyre, Lebanon
| | - Lama M. Fawaz
- Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Quebec, Canada
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19
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Shah AB, Cho H, Shim SH. Exploring the bioactive landscape: peptides and non-peptides from the human microbiota. NPJ Biofilms Microbiomes 2025; 11:76. [PMID: 40341751 PMCID: PMC12062242 DOI: 10.1038/s41522-025-00713-x] [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: 12/12/2024] [Accepted: 04/28/2025] [Indexed: 05/11/2025] Open
Abstract
The human microbiota, consisting of trillions of bacteria from six main phyla, produces peptide and non-peptide secondary metabolites which have antibacterial properties vital to medicine and biotechnology. These metabolites influence biological processes linked to diseases, yet much remains unknown. This review explores their structures and functions, aiming to spur novel metabolite discovery and advance drug development.
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Affiliation(s)
- Abdul Bari Shah
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
| | - Hyeonjae Cho
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
| | - Sang Hee Shim
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
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20
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Noman AM, Sultan MT, Maaz M, Mazhar A, Tariq N, Imran M, Hussain M, Mujtaba A, Abdelgawad MA, Mostafa EM, Ghoneim MM, Selim S, Al Jbawi E. Nutraceutical Potential of Anthocyanins: A Comprehensive Treatise. Food Sci Nutr 2025; 13:e70164. [PMID: 40330208 PMCID: PMC12050221 DOI: 10.1002/fsn3.70164] [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: 01/25/2025] [Revised: 03/05/2025] [Accepted: 04/01/2025] [Indexed: 05/08/2025] Open
Abstract
Anthocyanins (Anthos; flower and kyanos; blue) are natural coloring compounds from the flavonoids class that include cyanidin, peonidin, delphinidin, malvidin, pelargonidin, and petunidin. Recently, the role of anthocyanins in disease prevention, especially inflammation, diabetes, cancer, neuro-disorders, hepato-renal protective, and immuno-modulation properties has been highlighted. The current review covered the literature on the pharmacokinetics and pharmacological effects of anthocyanins, especially absorption, distribution, metabolism, and excretion (ADME). The discussion on molecular mechanisms underlying their therapeutic effects is the limelight of the article. The GLUT1, GLUT3, SGLT1, SMCT1, and SMCT2 are the main carriers involved in the transportation of anthocyanins in the gastrointestinal tract. The anthocyanins exert their anticancer effects by reducing the expression of IL-6, IL-1β, TNF-β, COX-2, downregulation of NF-kB, EZH2, MDR1, Akt, and modulation of P13K/AKT and AMPK/mTOR pathways. The reduction in α-amylase and α-glucosidase and improved FFAR1 activity results in antidiabetic effects. The regulation of PGC-1α/NRF2/TFAM, p-PI3K/Akt/GSK3β, and Nrf2/HO-1 prevents neurodegeneration. The anthocyanins impose hepato-renal protective effects via ameliorating NLRP3 inflammasome, inhibiting MDA, GSSG, iNOS, HO-1, ICAM-1, β2-microglobulin, and MPO activity, and improved SOD, CAT, and GSH activity. Anthocyanins promote beneficial gut microbiota and enhance SCFA production, thus inhibiting pro-inflammatory markers. The immuno-modulatory impact of anthocyanins involves the reduction of CRP, P-selectin, C1q, and C4. Anthocyanins reduce LDL, VLDL, TGs, and TC via improved GBA and upregulation of ATP6 V0C, ZO-1, and ATG4D expression. The WHO/FAO suggested that 2.5 mg/kg/day of grape-skin extracts of anthocyanins are safe, and China recommended that 50 mg/day of anthocyanins are safe for consumption. In a nutshell, the multifaceted health benefits of anthocyanins make them promising candidates for disease prevention and therapeutic interventions.
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Affiliation(s)
- Ahmad Mujtaba Noman
- Department of Human Nutrition, Faculty of Food Science and NutritionBahauddin Zakariya UniversityMultanPakistan
- TIMES InstituteMultanPakistan
| | - Muhammad Tauseef Sultan
- Department of Human Nutrition, Faculty of Food Science and NutritionBahauddin Zakariya UniversityMultanPakistan
| | - Muhammad Maaz
- Department of Human Nutrition, Faculty of Food Science and NutritionBahauddin Zakariya UniversityMultanPakistan
| | - Aimen Mazhar
- Department of Human Nutrition, Faculty of Food Science and NutritionBahauddin Zakariya UniversityMultanPakistan
| | - Naima Tariq
- Departmnet of Food Science and Technology, Faculty of Food Science and NutritionBahauddin Zakariya UniversityMultanPakistan
| | - Muhammad Imran
- Department of Food Science and TechnologyUniversity of NarowalNarowalPakistan
| | - Muzzamal Hussain
- Department of Food ScienceGovernment College University FaisalabadFaisalabadPakistan
| | - Ahmed Mujtaba
- Department of Food Sciences and Technology, Faculty of Engineering Sciences and TechnologyHamdard University IslamabadIslamabadPakistan
| | - Mohamed A. Abdelgawad
- Department of Pharmaceutical Chemistry, College of PharmacyJouf UniversitySakakaSaudi Arabia
| | - Ehab M. Mostafa
- Department of Pharmacognosy, College of PharmacyJouf UniversitySakakaSaudi Arabia
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of PharmacyAlMaarefa UniversityRiyadhSaudi Arabia
| | - Samy Selim
- Department of Clinical Laboratory Sciences, College of Applied Medical SciencesJouf UniversitySakakaSaudi Arabia
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Bauer Estrada K, Conde-Martínez N, Acosta-González A, Díaz-Barrera LE, Rodríguez-Castaño GP, Quintanilla-Carvajal MX. Synbiotics of encapsulated Limosilactobacillus fermentum K73 promotes in vitro favorable gut microbiota shifts and enhances short-chain fatty acid production in fecal samples of children with autism spectrum disorder. Food Res Int 2025; 209:116227. [PMID: 40253179 DOI: 10.1016/j.foodres.2025.116227] [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: 11/21/2024] [Revised: 02/23/2025] [Accepted: 03/11/2025] [Indexed: 04/21/2025]
Abstract
Modulation of the gut microbiota has emerged as a promising approach for addressing the gastrointestinal and neurodevelopmental symptoms associated with autism spectrum disorder (ASD). Consequently, this study aimed to evaluate the impact of four formulated synbiotics comprising Limoscilactobacillus fermentum K73, high-oleic palm oil and whey, on the gut microbiota composition of Colombian children with and without ASD. These components were encapsulated through high-shear emulsification and spray drying. The four synbiotics and their individual components were subjected to in vitro digestion and fermentation using samples of Colombian children gut microbiota. Short-chain fatty acids (SCFAs), including lactic, acetic, propionic, and butyric acids, were quantified using HPLC-DAD, while serotonin was determined by an ELISA kit after in vitro fermentations. Changes in microbial structure were assessed by the sequencing of the 16S rRNA gene via next-generation sequencing (NGS). The results revealed a decrease in the abundance of genera like Bacteroides and Dorea in ASD-associated samples after the treatment with the synbiotics. Conversely, an increase in the relative abundance of probiotic-related genera, including Lactobacillus, Streptococcus, and Anaerostipes, was observed. Furthermore, the analysis of SCFAs and serotonin indicated that the synbiotic intervention resulted in an elevated butyric acid and microbial serotonin synthesis, alongside a decrease in propionic acid, which is changes considered beneficial in the context of ASD. This evidence suggests that synbiotics of L. fermentum K73 could represent a promising live biotherapeutic strategy for modulating the gut microbiota of children with ASD.
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Affiliation(s)
- Katherine Bauer Estrada
- Biosciences Doctorate, Engineering Department, Universidad de La Sabana, Chía, Colombia; Engineering Department, Universidad de La Sabana, Chía, Colombia
| | | | - Alejandro Acosta-González
- Engineering Department, Universidad de La Sabana, Chía, Colombia; Unisabana Center for Translational Science, School of Medicine, Universidad de La Sabana, Chía, Colombia
| | | | | | - María Ximena Quintanilla-Carvajal
- Engineering Department, Universidad de La Sabana, Chía, Colombia; Unisabana Center for Translational Science, School of Medicine, Universidad de La Sabana, Chía, Colombia.
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22
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Sathitkowitchai W, Mok K, Udomsri P, Nitisinprasert S, Nakphaichit M. Synergistic activity of synbiotic blend between Lactococcus lactis KAFF 1-4 and fibersol-2 on gut microbiota modulation and anti-VRE properties. 3 Biotech 2025; 15:133. [PMID: 40255450 PMCID: PMC12006641 DOI: 10.1007/s13205-025-04298-2] [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: 10/06/2024] [Accepted: 04/03/2025] [Indexed: 04/22/2025] Open
Abstract
The study evaluated the effectiveness of a synbiotic blend containing Lactococcus lactis KA-FF 1-4 and Fibersol-2 in modulating gut microbiota and inhibiting vancomycin-resistant Enterococcus (VRE). Compared to probiotic or prebiotic treatments alone, the synbiotic blend significantly altered the gut microbiota composition, increasing beneficial bacteria like Blautia, Clostridium, Parabacteroides, Prevotella, and Roseburia, while reducing VRE abundance. Moreover, the synbiotic treatment showed an increase in short-chain fatty acid (SCFA) concentrations, particularly acetate, propionate, and butyrate. Correlation analysis revealed that enriched taxa in the synbiotic treatment were positively associated with higher SCFA levels. These findings highlight the potential of synbiotic formulations in improving gut microbiota balance and combating antibiotic-resistant pathogens like VRE.
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Affiliation(s)
- Witida Sathitkowitchai
- Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
| | - Kevin Mok
- Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
- Center of Excellence for Microbiota Innovation, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
| | - Patkakorn Udomsri
- Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
| | - Sunee Nitisinprasert
- Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
- Center of Excellence for Microbiota Innovation, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
- Center for Advanced Studies for Agriculture and Food, Kasetsart University Institute for Advanced Studies, Kasetsart University (CASAF, NRU-KU), Bangkok, 10900 Thailand
| | - Massalin Nakphaichit
- Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
- Center of Excellence for Microbiota Innovation, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
- Center for Advanced Studies for Agriculture and Food, Kasetsart University Institute for Advanced Studies, Kasetsart University (CASAF, NRU-KU), Bangkok, 10900 Thailand
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Maqsood S, Arshad MT, Ikram A, Gnedeka KT. Fruit-Based Diet and Gut Health: A Review. Food Sci Nutr 2025; 13:e70159. [PMID: 40313793 PMCID: PMC12041667 DOI: 10.1002/fsn3.70159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 02/08/2025] [Accepted: 03/09/2025] [Indexed: 05/03/2025] Open
Abstract
Gut health is essential to the overall well-being of a human being due to its implication on digestion, the performance of the immune system, and nutritional absorption. The gut microbiota represents an intricate ecology of bacteria, fungi, and viruses, important in regulating the immune response and maintaining intestinal health. Fruit-based diets have developed as an essential constituent in gut health, and current studies highlight nutrition in modulating gut microbiota composition and activity. Rich in fiber, polyphenols, vitamins, and antioxidants, fruits also expand immunological function, subordinate inflammation in the stomach, and boost microbial diversity. The article reviews the benefits of fruit-derived dietary fibers, which assist as prebiotics in fostering the development of beneficial gut microbiota and decreasing intestinal inflammation. These antioxidants in fruits include flavonoids and carotenoids, whose immunomodulatory properties are under investigation for therapeutic use in autoimmune diseases, infections, and inflammatory bowel disease (IBD). Some fruits of particular interest include bananas, apples, citrus, and berries, as studies have consistently shown their immunomodulatory and gastrointestinal effects. There are still barriers to increasing fruit intake, including socioeconomic restrictions and the need for personalized nutritional counseling. The review fills an existing gap in the literature. It encourages enhanced immune and gastrointestinal well-being by combining the most recent research with practical recommendations on implementing fruit-based diets into daily nutrition.
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Affiliation(s)
- Sammra Maqsood
- National Institute of Food Science and TechnologyUniversity of Agriculture FaisalabadFaisalabadPakistan
| | - Muhammad Tayyab Arshad
- University Institute of Food Science and TechnologyThe University of LahoreLahorePakistan
| | - Ali Ikram
- University Institute of Food Science and TechnologyThe University of LahoreLahorePakistan
| | - Kodjo Théodore Gnedeka
- Togo Laboratory: Applied Agricultural Economics Research Team (ERE2A)University of LoméLoméTogo
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24
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Ajith TA, Anita B. Impact of Gut Microbiota and Probiotics on Rheumatoid Arthritis: A Potential Treatment Challenge. Int J Rheum Dis 2025; 28:e70266. [PMID: 40329613 DOI: 10.1111/1756-185x.70266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 04/02/2025] [Accepted: 04/30/2025] [Indexed: 05/08/2025]
Abstract
Over the past few decades, there has been a surge in global study on the relationship between gut microbiota and human health. Numerous human illnesses have been linked to dysbiosis. Gram-positive firmicutes and Gram-negative bacteroidetes are the two leading bacterial phyla that make up 90% of the gut microbiome. Many symbionts in the gut environment establish intricate relationships with host defense to stop both local and non-native dangerous bacteria from colonizing and invading. Dysbiosis alters the paracellular route and damages the epithelium, enabling them to penetrate the epithelium and come into contact with the immune cells. Impaired intestinal barrier function, immune regulation mediated by metabolites derived from the gut microbiota, posttranslational modification of host proteins such as increased citrullination, regulation of the gut microbiota's effect on immune cells, intestinal epithelial cell autophagy, interaction between the microbiome and human leukocyte antigen alleles, and interaction with microRNAs are some of the mechanisms involved in rheumatoid arthritis (RA). The gut microbiota, Prevotella copri, and Collinsella spp. were shown to be higher in the early/preclinical phases of RA, while Bacteroidetes, Bifidobacteria, and Eubacterium rectale were found to be lower. Probiotic-based early dietary intervention may reduce inflammation and slow the rate of joint deterioration, and such intervention can also aid in the restoration of gut microbiota equilibrium. This review article describes the gut microbial dysbiosis and role of probiotics in RA.
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Affiliation(s)
| | - Bejoy Anita
- Department of General Medicine, Amala Institute of Medical Sciences, Thrissur, Kerala, India
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25
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Zeyneb H, Song Y, Wang L, Zheng J, Wang W, Pei H, Cao X. Preventive effect of quinoa polysaccharides on lipopolysaccharide-induced inflammation in mice through gut microbiota regulation. Int J Biol Macromol 2025; 307:141899. [PMID: 40068754 DOI: 10.1016/j.ijbiomac.2025.141899] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 02/28/2025] [Accepted: 03/07/2025] [Indexed: 03/14/2025]
Abstract
Inflammation significantly influences the development of gastrointestinal (GI) diseases such as inflammatory bowel diseases (IBD)and ulcerative colitis, which disrupts normal digestive functions, leading to tissue damage and various symptoms. This research explores the preventive effects of quinoa polysaccharides (QPS) on lipopolysaccharide (LPS)-induced systemic acute inflammation in mice and their mechanism of action. The findings revealed that QPS alleviated LPS-induced inflammation symptoms, enhanced the mice behavior score and their immune organ index, reduced pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) levels, elevated the expression level of tight junction proteins (ZO-1, MUC2). Additionally, the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were improved via QPS administration. Further, our research suggested that QPS enhanced the diversity and abundance of gut microbiota compared to that of LPS mice, leading to an increase in the short-chain fatty acids in mice feces. Linear discriminant analysis (LDA) effect size (LEfSe) showed that QPS administration could lead to a range of gut biomarkers, promoting the enhancement of polysaccharide-metabolizing bacteria. The results of 16S rRNA sequencing indicated that QPS alleviates LPS-induced inflammation by enhancing the richness of beneficial bacteria such as Bacteroides and Lactobacillus. Linear discriminant analysis (LDA) effect size (LEfSe) showed that QPS administration could lead to a range of gut biomarkers, promoting the enhancement of polysaccharide-metabolizing bacteria. UPLC Q-TOF-MS was performed to analyze metabolites in the fecal samples. LPS administration significantly altered metabolite levels detected in mice feces in which some metabolites have decreased such as xanthosine and hypoxanthine while an increase in some metabolites in mice that received QPS, metabolomics analysis showed the beneficial effects of QPS primarily mediated via amino and bile acid-related metabolism pathways. Our research could offer the basis for further studies and applications of quinoa polysaccharides.
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Affiliation(s)
- Hitache Zeyneb
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University, Beijing 100048, China
| | - Ya Song
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University, Beijing 100048, China
| | - Lin Wang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University, Beijing 100048, China
| | - Jimin Zheng
- College of Chemistry, Beijing Normal University, Beijing 100875, China
| | - Wei Wang
- Institute of Analysis and Testing, Beijing Academy of Science and Technology (Beijing Center for Physical &Chemical Analysis), Beijing 100094, China
| | - Hairun Pei
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University, Beijing 100048, China.
| | - Xueli Cao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University, Beijing 100048, China.
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26
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Maubach G, Kanthasamy AK, Gogia S, Naumann M. The enigma of maladaptation in gastric pathophysiology. Trends Cancer 2025; 11:448-461. [PMID: 39984410 DOI: 10.1016/j.trecan.2025.01.014] [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: 11/14/2024] [Revised: 01/24/2025] [Accepted: 01/29/2025] [Indexed: 02/23/2025]
Abstract
Despite a decline in global incidence, gastric cancer (GC) remains a major health concern. The development of GC is a sequential, multistage maladaptive process involving numerous different factors. Understanding the complexity of GC development is crucial for early detection, effective treatment, and, ultimately, prevention. In this respect, identifying the impact of risk factors contributing to the emergence or progression of GC, such as Helicobacter pylori infection, host and bacterial genetics, alcohol consumption, smoking, and preserved foods, will aid in combatting this disease. In this review, we focus on recent developments in understanding the role of the microbiome, dysfunctional molecular pathways, and immune evasion in gastric pathophysiology. We also highlight challenges and advances in treatment of GC.
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Affiliation(s)
- Gunter Maubach
- Institute of Experimental Internal Medicine, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Arun K Kanthasamy
- Institute of Experimental Internal Medicine, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Sandro Gogia
- Institute of Experimental Internal Medicine, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany.
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27
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Flores-Treviño S, Bocanegra-Ibarias P, Salas-Treviño D, Ramírez-Elizondo MT, Pérez-Alba E, Camacho-Ortiz A. Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases. Expert Opin Biol Ther 2025; 25:1-14. [PMID: 40134274 DOI: 10.1080/14712598.2025.2484303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 03/21/2025] [Indexed: 03/27/2025]
Abstract
INTRODUCTION The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases. AREAS COVERED Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed. EXPERT OPINION In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.
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Affiliation(s)
- Samantha Flores-Treviño
- Department of Infectious Diseases, University Hospital "Dr. José Eleuterio González", Autonomous University of Nuevo Leon, Monterrey, Mexico
| | - Paola Bocanegra-Ibarias
- Department of Infectious Diseases, University Hospital "Dr. José Eleuterio González", Autonomous University of Nuevo Leon, Monterrey, Mexico
| | - Daniel Salas-Treviño
- Department of Infectious Diseases, University Hospital "Dr. José Eleuterio González", Autonomous University of Nuevo Leon, Monterrey, Mexico
| | - María Teresa Ramírez-Elizondo
- Department of Infectious Diseases, University Hospital "Dr. José Eleuterio González", Autonomous University of Nuevo Leon, Monterrey, Mexico
| | - Eduardo Pérez-Alba
- Department of Infectious Diseases, University Hospital "Dr. José Eleuterio González", Autonomous University of Nuevo Leon, Monterrey, Mexico
| | - Adrián Camacho-Ortiz
- Department of Infectious Diseases, University Hospital "Dr. José Eleuterio González", Autonomous University of Nuevo Leon, Monterrey, Mexico
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28
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Diacova T, Cifelli CJ, Davis CD, Holscher HD, Kable ME, Lampe JW, Latulippe ME, Swanson KS, Karl JP. Best Practices and Considerations for Conducting Research on Diet-Gut Microbiome Interactions and Their Impact on Health in Adult Populations: An Umbrella Review. Adv Nutr 2025; 16:100419. [PMID: 40180180 PMCID: PMC12056254 DOI: 10.1016/j.advnut.2025.100419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 03/19/2025] [Accepted: 03/27/2025] [Indexed: 04/05/2025] Open
Abstract
Diet modulates gut microbiome composition and function. However, determining causal links between diet-gut microbiome interactions and human health is complicated by inconsistencies in the evidence, arising partially from variability in research methods and reporting. Widespread adoption of standardized best practices would advance the field but require those practices to be identified, consolidated, and discussed. This umbrella review aimed to identify recommended best practices, define existing gaps, and collate considerations for conducting research on diet-gut microbiome interactions and their impact on human health outcomes. Reviews meeting inclusion criteria and published after 2013 were identified using a systematic search. Recommendations, considerations, and gaps relating to the best practices associated with study design, participant selection, dietary intervention/assessment, biological sample collection, and data analysis and reporting were extracted and consolidated. Eight narrative reviews were included. Several general points of agreement were identified, and a recurring theme was that best practices are dependent upon the research aims, outcomes, and feasibility. Multiple gaps were also identified. Some, such as suboptimal diet assessment methods and lack of validated dietary intake biomarkers, are particularly relevant to nutrition science. Others, including defining a "healthy" gut microbiome and the absence of standardized sample and data collection/analysis protocols, were relevant specifically to gut microbiome research. Gaps specific to diet-gut microbiome research include the underrepresentation of microbiome-modulating dietary components in food databases, lack of knowledge regarding interventions eliciting changes in the gut microbiome to confer health benefits, lack of in situ measurement methods, and the need to further develop and refine statistical approaches for integrating diet and gut microbiome data. Future research and cross-disciplinary exchange will address these gaps and evolve the best practices. In the interim, the best practices and considerations discussed herein, and the publications from which that information was extracted provide a roadmap for conducting diet-gut microbiome research. This trial was registered at PROSPERO as CRD42023437645.
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Affiliation(s)
- Tatiana Diacova
- Graduate Group in Nutritional Biology, University of California Davis, Davis, CA, United States
| | | | - Cindy D Davis
- Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, United States
| | - Hannah D Holscher
- Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL, United States; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, United States
| | - Mary E Kable
- Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, United States
| | - Johanna W Lampe
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Marie E Latulippe
- Institute for the Advancement of Food and Nutrition Sciences, Washington, DC, United States
| | - Kelly S Swanson
- Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, United States; Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, United States
| | - J Philip Karl
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States.
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Muttiah B, Hanafiah A. Gut Microbiota and Cardiovascular Diseases: Unraveling the Role of Dysbiosis and Microbial Metabolites. Int J Mol Sci 2025; 26:4264. [PMID: 40362500 PMCID: PMC12072866 DOI: 10.3390/ijms26094264] [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: 04/09/2025] [Revised: 04/29/2025] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
Cardiovascular diseases (CVDs), including heart failure (HF), hypertension, myocardial infarction (MI), and atherosclerosis, are increasingly linked to gut microbiota dysbiosis and its metabolic byproducts. HF, affecting over 64 million individuals globally, is associated with systemic inflammation and gut barrier dysfunction, exacerbating disease progression. Similarly, hypertension and MI correlate with reduced microbial diversity and an abundance of pro-inflammatory bacteria, contributing to vascular inflammation and increased cardiovascular risk. Atherosclerosis is also influenced by gut dysbiosis, with key microbial metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) playing crucial roles in disease pathogenesis. Emerging evidence highlights the therapeutic potential of natural compounds, including flavonoids, omega-3 fatty acids, resveratrol, curcumin, and marine-derived bioactives, which modulate the gut microbiota and confer cardioprotective effects. These insights underscore the gut microbiota as a critical regulator of cardiovascular health, suggesting that targeting dysbiosis may offer novel preventive and therapeutic strategies. Further research is needed to elucidate underlying mechanisms and optimize microbiome-based interventions for improved cardiovascular outcomes.
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Affiliation(s)
- Barathan Muttiah
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Alfizah Hanafiah
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- GUT Research Group, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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30
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Sharma S, Sharma A, Sodhi GK, George N, Alarjani KM, Mukherjee A, Kumar Rath S, Kaur R, Dwibedi V. Staphylococcus epidermidis SAS1: new probiotic candidate for obesity and allergy treatment their mechanistic insights and cytotoxicity evaluation. Front Microbiol 2025; 16:1546687. [PMID: 40371109 PMCID: PMC12075200 DOI: 10.3389/fmicb.2025.1546687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 04/07/2025] [Indexed: 05/16/2025] Open
Abstract
Background Probiotics are live bacteria that provides numerous healthy and beneficial effects to the consumers. The present study aimed to investigate the effect of a probiotic candidate Staphylococcus epidermidis SAS1, in immunoregulation and obesity management. Methods : This probiotic candidate was isolated from a soil sample collected from a region of fruit waste decomposition. In vitro cytotoxicity was assessed using the THP-1 (human leukemia monocytic cell line) cells using MTT assay. Results An IC50 value of 47.52 ± 0.18 μg/mL and cell shrinkage were observed along with the release of cellular content of THP-1 cells. The higher production of reactive oxygen species and lesser release of interleukins (IL-4, 5, and 13) are attributed to the antiallergic potential of this strain. Furthermore, in vitro cytotoxicity evaluation using 3T3-L1 cells identified this strain as a promising candidate for anti-obesity treatment. The observed IC50 value was 514.4 ± 0.061 μg/mL. Discussion This extract was shown to have good lipase-inhibiting enzyme activity and was reported to prevent adipogenesis, depicted by increased HDL levels and decreased LDL and triglyceride levels. These results suggested that Staphylococcus epidermidis SAS1 may have therapeutic use in the treatment of obesity and allergies.
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Affiliation(s)
- Sonia Sharma
- University Institute of Biotechnology, Chandigarh University, Mohali, India
| | - Aarjoo Sharma
- Department of Microbiology, Panjab University, Chandigarh, India
| | - Gurleen Kaur Sodhi
- University Institute of Biotechnology, Chandigarh University, Mohali, India
| | - Nancy George
- University Institute of Biotechnology, Chandigarh University, Mohali, India
| | - Khaloud Mohammed Alarjani
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Arkadeep Mukherjee
- Department of Civil Engineering, Yeungnam University, Gyeongsan, Republic of Korea
| | - Santosh Kumar Rath
- School of Pharmaceuticals and Population Health Informatics, Faculty of Pharmacy, DIT University, Dehradun, India
| | - Ramandeep Kaur
- Department of Biotechnology, Chandigarh Group of Colleges, Landran, India
| | - Vagish Dwibedi
- University Institute of Biotechnology, Chandigarh University, Mohali, India
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31
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Zhang R, Hu W, Zhong S, Chen W, Chen M, Yu Q. Impact of Enterococcus faecium Kimate-X on Reducing Stress in Dogs Through Gut Microbiota Modulation. Vet Sci 2025; 12:412. [PMID: 40431505 PMCID: PMC12115767 DOI: 10.3390/vetsci12050412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Revised: 04/07/2025] [Accepted: 04/16/2025] [Indexed: 05/29/2025] Open
Abstract
Stress in dog breeding leads to significant physiological and psychological burdens, including anxiety, reduced appetite, weakened immune function, gut microbiota imbalance, and even death. Currently, there are various pharmacological interventions for stress management, but few focus on gut health. This study evaluates the potential of a novel strain, Enterococcus faecium Kimate-X, in alleviating transport stress and improving gut health in dogs, providing an alternative to traditional pharmacological treatments. In vitro experiments showed that Kimate-X significantly enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) while reducing the levels of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in RAW 264.7 macrophage cells. In vivo, dogs supplemented with Kimate-X exhibited significantly lower cortisol levels after transport, indicating reduced stress. Metagenomic analysis revealed increased gut microbiota diversity and higher concentrations of short-chain fatty acids (acetate, propionate, and butyrate) in fecal samples. This study systematically uncovers the mechanism by which Enterococcus faecium Kimate-X alleviates transport stress through modulation of the gut microbiota. These findings provide new scientific evidence supporting the use of probiotics as a novel approach to stress management in animals.
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Affiliation(s)
- Rui Zhang
- Laboratory of Microbiology, Immunology and Metabolism, Diprobio (Shanghai) Co., Ltd., Shanghai 200050, China; (W.H.); (S.Z.); (W.C.); (M.C.); (Q.Y.)
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210014, China
| | - Wanjin Hu
- Laboratory of Microbiology, Immunology and Metabolism, Diprobio (Shanghai) Co., Ltd., Shanghai 200050, China; (W.H.); (S.Z.); (W.C.); (M.C.); (Q.Y.)
| | - Saiwei Zhong
- Laboratory of Microbiology, Immunology and Metabolism, Diprobio (Shanghai) Co., Ltd., Shanghai 200050, China; (W.H.); (S.Z.); (W.C.); (M.C.); (Q.Y.)
| | - Weiyang Chen
- Laboratory of Microbiology, Immunology and Metabolism, Diprobio (Shanghai) Co., Ltd., Shanghai 200050, China; (W.H.); (S.Z.); (W.C.); (M.C.); (Q.Y.)
| | - Meiru Chen
- Laboratory of Microbiology, Immunology and Metabolism, Diprobio (Shanghai) Co., Ltd., Shanghai 200050, China; (W.H.); (S.Z.); (W.C.); (M.C.); (Q.Y.)
| | - Qinghua Yu
- Laboratory of Microbiology, Immunology and Metabolism, Diprobio (Shanghai) Co., Ltd., Shanghai 200050, China; (W.H.); (S.Z.); (W.C.); (M.C.); (Q.Y.)
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210014, China
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Mahgoup EM. "Gut Microbiota as a Therapeutic Target for Hypertension: Challenges and Insights for Future Clinical Applications" "Gut Microbiota and Hypertension Therapy". Curr Hypertens Rep 2025; 27:14. [PMID: 40261509 DOI: 10.1007/s11906-025-01331-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2025] [Indexed: 04/24/2025]
Abstract
PURPOSE OF REVIEW Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management. RECENT FINDINGS Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.
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Affiliation(s)
- Elsayed M Mahgoup
- Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
- Department of Internal Medicine, Division of Cardiovascular Medicine, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
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Nemati MH, Yazdanpanah E, Kazemi R, Orooji N, Dadfar S, Oksenych V, Haghmorad D. Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential. BIOLOGY 2025; 14:435. [PMID: 40282300 PMCID: PMC12025160 DOI: 10.3390/biology14040435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/11/2025] [Accepted: 04/16/2025] [Indexed: 04/29/2025]
Abstract
Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.
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Affiliation(s)
- Mohammad Hosein Nemati
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Esmaeil Yazdanpanah
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
| | - Roya Kazemi
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Niloufar Orooji
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Sepehr Dadfar
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Valentyn Oksenych
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
| | - Dariush Haghmorad
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
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Ionescu VA, Diaconu CC, Gheorghe G, Mihai MM, Diaconu CC, Bostan M, Bleotu C. Gut Microbiota and Colorectal Cancer: A Balance Between Risk and Protection. Int J Mol Sci 2025; 26:3733. [PMID: 40332367 PMCID: PMC12028331 DOI: 10.3390/ijms26083733] [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: 03/21/2025] [Revised: 04/11/2025] [Accepted: 04/14/2025] [Indexed: 05/08/2025] Open
Abstract
The gut microbiome, a complex community of microorganisms residing in the intestinal tract, plays a dual role in colorectal cancer (CRC) development, acting both as a contributing risk factor and as a protective element. This review explores the mechanisms by which gut microbiota contribute to CRC, emphasizing inflammation, oxidative stress, immune evasion, and the production of genotoxins and microbial metabolites. Fusobacterium nucleatum, Escherichia coli (pks+), and Bacteroides fragilis promote tumorigenesis by inducing chronic inflammation, generating reactive oxygen species, and producing virulence factors that damage host DNA. These microorganisms can also evade the antitumor immune response by suppressing cytotoxic T cell activity and increasing regulatory T cell populations. Additionally, microbial-derived metabolites such as secondary bile acids and trimethylamine-N-oxide (TMAO) have been linked to carcinogenic processes. Conversely, protective microbiota, including Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii, contribute to intestinal homeostasis by producing short-chain fatty acids (SCFAs) like butyrate, which exhibit anti-inflammatory and anti-carcinogenic properties. These beneficial microbes enhance gut barrier integrity, modulate immune responses, and inhibit tumor cell proliferation. Understanding the dynamic interplay between pathogenic and protective microbiota is essential for developing microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, to prevent or treat CRC. Future research should focus on identifying microbial biomarkers for early CRC detection and exploring personalized microbiome-targeted therapies. A deeper understanding of host-microbiota interactions may lead to innovative strategies for CRC management and improved patient outcomes.
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Affiliation(s)
- Vlad Alexandru Ionescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (G.G.); (M.-M.M.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Camelia Cristina Diaconu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (G.G.); (M.-M.M.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Academy of Romanian Scientists, 050085 Bucharest, Romania;
| | - Gina Gheorghe
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (G.G.); (M.-M.M.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Mara-Madalina Mihai
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (G.G.); (M.-M.M.)
- Department of Oncologic Dermathology, “Elias” University Emergency Hospital, 010024 Bucharest, Romania
| | - Carmen Cristina Diaconu
- Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania; (C.C.D.); (M.B.)
| | - Marinela Bostan
- Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania; (C.C.D.); (M.B.)
- Department of Immunology, “Victor Babes” National Institute of Pathology, 050096 Bucharest, Romania
| | - Coralia Bleotu
- Academy of Romanian Scientists, 050085 Bucharest, Romania;
- Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania; (C.C.D.); (M.B.)
- Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060023 Bucharest, Romania
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Dakal TC, Xu C, Kumar A. Advanced computational tools, artificial intelligence and machine-learning approaches in gut microbiota and biomarker identification. FRONTIERS IN MEDICAL TECHNOLOGY 2025; 6:1434799. [PMID: 40303946 PMCID: PMC12037385 DOI: 10.3389/fmedt.2024.1434799] [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: 07/23/2024] [Accepted: 10/16/2024] [Indexed: 05/02/2025] Open
Abstract
The microbiome of the gut is a complex ecosystem that contains a wide variety of microbial species and functional capabilities. The microbiome has a significant impact on health and disease by affecting endocrinology, physiology, and neurology. It can change the progression of certain diseases and enhance treatment responses and tolerance. The gut microbiota plays a pivotal role in human health, influencing a wide range of physiological processes. Recent advances in computational tools and artificial intelligence (AI) have revolutionized the study of gut microbiota, enabling the identification of biomarkers that are critical for diagnosing and treating various diseases. This review hunts through the cutting-edge computational methodologies that integrate multi-omics data-such as metagenomics, metaproteomics, and metabolomics-providing a comprehensive understanding of the gut microbiome's composition and function. Additionally, machine learning (ML) approaches, including deep learning and network-based methods, are explored for their ability to uncover complex patterns within microbiome data, offering unprecedented insights into microbial interactions and their link to host health. By highlighting the synergy between traditional bioinformatics tools and advanced AI techniques, this review underscores the potential of these approaches in enhancing biomarker discovery and developing personalized therapeutic strategies. The convergence of computational advancements and microbiome research marks a significant step forward in precision medicine, paving the way for novel diagnostics and treatments tailored to individual microbiome profiles. Investigators have the ability to discover connections between the composition of microorganisms, the expression of genes, and the profiles of metabolites. Individual reactions to medicines that target gut microbes can be predicted by models driven by artificial intelligence. It is possible to obtain personalized and precision medicine by first gaining an understanding of the impact that the gut microbiota has on the development of disease. The application of machine learning allows for the customization of treatments to the specific microbial environment of an individual.
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Affiliation(s)
- Tikam Chand Dakal
- Genome and Computational Biology Lab, Department of Biotechnology, Mohanlal Sukhadia University, Udaipur, India
| | - Caiming Xu
- Beckman Research Institute of City of Hope, Monrovia, CA, United States
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Abhishek Kumar
- Manipal Academy of Higher Education (MAHE), Manipal, India
- Institute of Bioinformatics, International Technology Park, Bangalore, India
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Abdul Manan M. Progress in Probiotic Science: Prospects of Functional Probiotic-Based Foods and Beverages. INTERNATIONAL JOURNAL OF FOOD SCIENCE 2025; 2025:5567567. [PMID: 40259922 PMCID: PMC12011469 DOI: 10.1155/ijfo/5567567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 03/27/2025] [Indexed: 04/23/2025]
Abstract
This comprehensive review explores the evolving role of probiotic-based foods and beverages, highlighting their potential as functional and "future foods" that could significantly enhance nutrition, health, and overall well-being. These products are gaining prominence for their benefits in gut health, immune support, and holistic wellness. However, their future success depends on addressing critical safety concerns and navigating administrative complexities. Ensuring that these products "do more good than harm" involves rigorous evaluations of probiotic strains, particularly those sourced from the human gastrointestinal tract. Lactic acid bacteria (LABs) serve as versatile and effective functional starter cultures for the development of probiotic foods and beverages. The review emphasizes the role of LABs as functional starter cultures and the development of precision probiotics in advancing these products. Establishing standardized guidelines and transparent practices is essential, requiring collaboration among regulatory bodies, industry stakeholders, and the scientific community. The review underscores the importance of innovation in developing "friendly bacteria," "super probiotics," precision fermentation, and effective safety assessments. The prospects of functional probiotic-based foods and beverages rely on refining these elements and adapting to emerging scientific advancements. Ultimately, empowering consumers with accurate information, fostering innovation, and maintaining stringent safety standards will shape the future of these products as trusted and beneficial components of a health-conscious society. Probiotic-based foods and beverages, often infused with LABs, a "friendly bacteria," are emerging as "super probiotics" and "future foods" designed to "do more good than harm" for overall health.
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Affiliation(s)
- Musaalbakri Abdul Manan
- Food Science and Technology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), MARDI Headquarters, Persiaran MARDI-UPM, Serdang, Selangor, Malaysia
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37
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Bonomo MG, D’Angelo S, Picerno V, Carriero A, Salzano G. Recent Advances in Gut Microbiota in Psoriatic Arthritis. Nutrients 2025; 17:1323. [PMID: 40284188 PMCID: PMC12030176 DOI: 10.3390/nu17081323] [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: 03/06/2025] [Revised: 04/04/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025] Open
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.
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Affiliation(s)
- Maria Grazia Bonomo
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
| | - Salvatore D’Angelo
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Valentina Picerno
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Antonio Carriero
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Giovanni Salzano
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
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Hakimiha N, Jahani Sherafat S, Laakso EL, Fekrazad R. Photobiomodulation and the oral-gut microbiome axis: therapeutic potential and challenges. Front Med (Lausanne) 2025; 12:1555704. [PMID: 40270495 PMCID: PMC12014685 DOI: 10.3389/fmed.2025.1555704] [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: 01/05/2025] [Accepted: 03/31/2025] [Indexed: 04/25/2025] Open
Abstract
This Perspective article explores the challenges associated with the direct application of photobiomodulation (PBM) to the gut and presents a novel hypothesis for indirect gut health modulation through oral microbiome alteration. Given the difficulties in delivering PBM effectively to deep gastrointestinal tissues, an alternative approach involves targeting the oral microbiome, which has a demonstrated relationship with the gut microbiome. Research indicates that PBM applied to the oral cavity could selectively alter microbial composition. This alteration may, via the oral-gut microbiome axis, indirectly impact gut health. This hypothesis, supported by preliminary studies, suggests that oral PBM could offer a promising non-invasive strategy for managing gut-related disorders. Furthermore, there may be a link between the oral microbiome and brain diseases. Given the proximity to the brain, PBM-induced changes in the oral microbiota could indirectly help prevent neurological disorders. However, further investigation is necessary to comprehensively elucidate the underlying mechanisms and therapeutic implications of this approach.
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Affiliation(s)
- Neda Hakimiha
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Somayeh Jahani Sherafat
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - E-Liisa Laakso
- Mater Research Institute, University of Queensland, South Brisbane, QLD, Australia
- School of Health Sciences and Social Work, Griffith University, Brisbane, QLD, Australia
| | - Reza Fekrazad
- Radiation Sciences Research Center (RSRC), AJA University of Medical Sciences, Tehran, Iran
- International Network for Photo Medicine and Photo Dynamic Therapy (INPMPDT), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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Liu HJ, Wu MC, Gau SY. Role of gut microbiota and mesenteric adipose tissue in the pathology of Crohn's disease: Potential therapeutic targets. World J Gastroenterol 2025; 31:102291. [PMID: 40248060 PMCID: PMC12001166 DOI: 10.3748/wjg.v31.i13.102291] [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: 10/14/2024] [Revised: 03/01/2025] [Accepted: 03/11/2025] [Indexed: 04/02/2025] Open
Abstract
This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn's disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.
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Affiliation(s)
- Han-Jung Liu
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Meng-Che Wu
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Division of Pediatric Gastroenterology, Children's Medical Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan
| | - Shuo-Yan Gau
- Department and Graduate Institute of Business Administration, National Taiwan University, Taipei 106319, Taiwan
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T-Thienprasert NP, Jaithon T, Klomkliew P, Chanchaem P, Suwanasopee T, Koonawootrittriron S, Kovitvadhi A, Chundang P, Pongprayoon P, Kityakarn S, Luksirikul P, Payungporn S. Comparative Analysis of the Gut Microbiota of Thai Indigenous Chicken Fed House Crickets. Animals (Basel) 2025; 15:1070. [PMID: 40218462 PMCID: PMC11987825 DOI: 10.3390/ani15071070] [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: 03/05/2025] [Revised: 03/30/2025] [Accepted: 03/31/2025] [Indexed: 04/14/2025] Open
Abstract
The gut microbiota is pivotal to chickens' overall health, influencing digestion, nutrient absorption, and immune function. Dietary compounds significantly impact gut microbiota composition. House crickets (Acheta domesticus) have emerged as an alternative protein source for animal feed, rich in proteins and beneficial fatty acids. This study compared the gut microbiota in the cecum and ileum of Thai indigenous chicken breeds (Betong Chicken, white feather with black bone chicken, and black feather with black bone chicken) fed with or without house crickets. Using Oxford Nanopore Technology of 16S rDNA, this study found a similar relative abundance of gut bacteria across groups, with dominant bacteria including Firmicute, Bacteroidetes, Proteobacteria, and Actinobacteria. LEfSe analysis identified differential abundance of beneficial bacteria, such as Ruminococcaceae, Rikenella, and Deferribacteres, in the cecum of the black feather with black bone chicken after cricket feeding. Additionally, Lactobacillaceae exhibited differential abundance in the ileum of this breed post-cricket diet. Consequently, this study provides new data into the gut microbiota of Thai indigenous chickens. It suggests that house cricket diets did not significantly alter microbiota diversity but may enhance beneficial bacteria in certain breeds.
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Affiliation(s)
| | - Titiradsadakorn Jaithon
- Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand;
| | - Pavit Klomkliew
- Center of Excellence in Systems Microbiology, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (P.K.); (P.C.)
| | - Prangwalai Chanchaem
- Center of Excellence in Systems Microbiology, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (P.K.); (P.C.)
| | - Thanathip Suwanasopee
- Department of Animal Science, Faculty of Agriculture, Kasetsart University, Bangkok 10900, Thailand; (T.S.); (S.K.)
| | - Skorn Koonawootrittriron
- Department of Animal Science, Faculty of Agriculture, Kasetsart University, Bangkok 10900, Thailand; (T.S.); (S.K.)
| | - Attawit Kovitvadhi
- Department of Physiology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand; (A.K.); (P.C.)
| | - Pipatpong Chundang
- Department of Physiology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand; (A.K.); (P.C.)
| | - Prapasiri Pongprayoon
- Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (P.P.); (S.K.); (P.L.)
- Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok 10900, Thailand
| | - Sutasinee Kityakarn
- Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (P.P.); (S.K.); (P.L.)
| | - Patraporn Luksirikul
- Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (P.P.); (S.K.); (P.L.)
- Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok 10900, Thailand
| | - Sunchai Payungporn
- Center of Excellence in Systems Microbiology, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (P.K.); (P.C.)
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Burke C, Glynn T, Jahangir C, Murphy C, Buckley N, Tangney M, Rahman A, Gallagher WM. Exploring the prognostic and predictive potential of bacterial biomarkers in non-gastrointestinal solid tumors. Expert Rev Mol Diagn 2025; 25:117-128. [PMID: 39973615 DOI: 10.1080/14737159.2025.2465743] [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: 08/19/2024] [Revised: 01/06/2025] [Accepted: 02/07/2025] [Indexed: 02/21/2025]
Abstract
INTRODUCTION Standard clinical parameters like tumor size, age, lymph node status, and molecular markers are used to predict progression risk and treatment response. However, exploring additional markers that reflect underlying biology could offer a more comprehensive understanding of the tumor microenvironment (TME). The TME influences tumor development, progression, disease severity, and survival, with tumor-associated bacteria posited to play significant roles. Studies on tumor-associated microbiota have focused on high bacterial-load sites such as the gut, oral cavity, and stomach, but interest is growing in non-gastrointestinal (GI) solid tumors, such as breast, lung, and pancreas. Microbe-based biomarkers, including Helicobacter pylori, human papillomavirus (HPV), and hepatitis B and C viruses, have proven valuable in predicting gastric, cervical, and renal cancers. AREAS COVERED Potential of prognostic and predictive bacterial biomarkers in non-GI solid tumors and the methodologies used. EXPERT OPINION Advances in techniques like 16S rRNA gene sequencing, qPCR, immunostaining, and in situ hybridization have enabled detailed analysis of difficult-to-culture microbes in solid tumors. However, to ensure reliable results, it is critical to standardize protocols, accurately align reads, address contamination, and maintain proper sample handling. This will pave the way for developing reliable bacterial markers that enhance prognosis, prediction, and personalized treatment planning.
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Affiliation(s)
- Caoimbhe Burke
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Thomas Glynn
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Chowdhury Jahangir
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Clodagh Murphy
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Niamh Buckley
- School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland
| | - Mark Tangney
- Cancer Research@UCC, University College Cork, Cork, Ireland
| | - Arman Rahman
- UCD School of Medicine, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - William M Gallagher
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
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Aleali MS, Mahapatro A, Maddineni G, Paladiya R, Jeanty H, Mohanty E, Mirchandani M, Jahanshahi A, Devulapally P, Alizadehasl A, Tariq MD, Hosseini Jebelli SF, Aliabadi AY, Hashemi SM, Amini-Salehi E. The impact of gut microbiome modulation on anthropometric indices in metabolic syndrome: an umbrella review. Ann Med Surg (Lond) 2025; 87:2263-2277. [PMID: 40212162 PMCID: PMC11981403 DOI: 10.1097/ms9.0000000000003140] [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: 08/23/2024] [Accepted: 02/25/2025] [Indexed: 04/13/2025] Open
Abstract
Background Metabolic syndrome (MetS) is a complex disorder characterized by a cluster of metabolic risk factors. Recent research highlights the gut microbiome's role in metabolic regulation, suggesting that modulation through probiotics, prebiotics, and synbiotics may provide a novel approach to managing MetS. This umbrella review aims to integrate insights from existing meta-analyses to explore how changes in gut microbiota influence key body measurement indicators in individuals with MetS. Methods A systematic search of PubMed, Scopus, and Web of Science databases identified meta-analyses that assessed the impact of probiotics, prebiotics, or synbiotics on anthropometric indices in MetS patients. Results The results indicated that microbial therapy leads to a significant reduction in body mass index (BMI) (SMD: -0.22; 95% CI: -0.35 to -0.09; P < 0.01) and waist circumference (WC) (SMD: -0.47; 95% CI: -0.80 to -0.15; P < 0.01). However, microbial therapy did not significantly affect body fat mass (SMD: -0.30; 95% CI: -0.64 to 0.02; P = 0.06), body fat percentage (SMD: -0.29; 95% CI: -0.62 to 0.03; P = 0.07), waist-to-hip ratio (SMD: -0.09; 95% CI: -0.46 to 0.28; P = 0.63), and weight (SMD: -0.06; 95% CI: -0.21 to 0.08; P = 0.37). Conclusions Gut microbial modulation, mainly through probiotics and synbiotics, shows promise in reducing BMI and WC in MetS patients. However, its effects on other anthropometric indices remain uncertain, warranting further high-quality research to fully understand microbial interventions' therapeutic potential.
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Affiliation(s)
- Maryam Sadat Aleali
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | | | | | - Ruchir Paladiya
- University of Connecticut Health Center, Farmington, Connecticut, USA
| | - Herby Jeanty
- The Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Elan Mohanty
- Gautam Maddineni, MD Mary Medical Center Apple Valley, Apple Valley, California, USA
| | | | - Ali Jahanshahi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Pavan Devulapally
- Social Determinants of Health Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Azin Alizadehasl
- Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | | | | | | | - Seyyed Mohammad Hashemi
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran
| | - Ehsan Amini-Salehi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
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Saleem MM, Masood S, Rahmatullah MM, Ayesha Imdad I, Mohammed Aslam Sange A, Nasr D. Gut Microbiota Dysbiosis and Its Role in the Development of Irritable Bowel Syndrome. Cureus 2025; 17:e83084. [PMID: 40438840 PMCID: PMC12116818 DOI: 10.7759/cureus.83084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2025] [Indexed: 06/01/2025] Open
Abstract
The gut microbiota refers to the diverse community of symbiotic and pathogenic microorganisms inhabiting the host digestive tract. This microbiome plays a vital role in maintaining the integrity of the digestive system. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. Although the pathophysiology of IBS remains unclear, recent studies suggest that the disruption of the gut microbiota (dysbiosis) may play a significant role. This study aims to examine the role of the gut microbiota in the development of IBS, analyze factors influencing the gut microbiome, and explore the potential for microbiota-targeted therapies. Relevant literature published from 2014 until 2024 was sourced from Google Scholar, PubMed, and Scopus using the keywords "microbiome", "irritable bowel syndrome", "dysbiosis", "faecal transplantation", and "probiotics". This review revealed consistent evidence of gut microbiota dysbiosis in individuals with IBS, characterized by altered microbial diversity, composition, and metabolic function. Contributing factors included a reduced abundance of beneficial commensals, overgrowth of potentially pathogenic species, and disrupted host-microbiota interactions. This dysbiosis was also frequently associated with symptom severity and specific IBS subtypes. Emerging evidence further highlights the role of diet, stress, and genetic factors in modulating gut microbiota and influencing IBS development. The growing body of research supports a strong link between dysbiosis and the pathogenesis and symptomatology of IBS. Understanding the microbial underpinnings of IBS opens avenues for potential diagnostic biomarkers and innovative therapeutic interventions aimed at restoring a balanced gut microbiota. However, further research is needed to elucidate the underlying mechanisms and translate these insights into effective clinical strategies for the management of IBS. This review underscores the significance of gut microbiota in IBS and its potential as a target for future therapeutic interventions.
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Affiliation(s)
- Manal M Saleem
- College of Medicine, Dubai Medical University, Dubai, ARE
| | - Sarah Masood
- College of Medicine, Dubai Medical University, Dubai, ARE
| | | | | | | | - Dina Nasr
- College of Medicine, Dubai Medical University, Dubai, ARE
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Wu J, Zhang X, Ayesha K, Khuram S, Cui J, Wang G, Yangzong Z, Shi M, Jiang X, Li L, Liu G, Zhao W, Song T. Multi-omics analysis of the mechanism of alfalfa and wheat-induced rumen flatulence in Xizang sheep. Microbiol Spectr 2025; 13:e0326824. [PMID: 40052788 PMCID: PMC11960438 DOI: 10.1128/spectrum.03268-24] [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: 12/14/2024] [Accepted: 01/26/2025] [Indexed: 04/03/2025] Open
Abstract
Rumen flatulence is a diet-related rumen disease in ruminants. This study induced a rumen flatulence model in Xizang sheep using alfalfa (HRF) and wheatgrass (MRF). The aim was to understand the rumen microbiota diversity in healthy and pathological states, host-microbiota interactions, and the molecular mechanisms of rumen flatulence. Results showed that the pH in the HRF and MRF groups was lower than that in the natural grass group (LRF). SCFA concentrations varied between groups: in HRF, 2-BA and CA increased; in MRF, 4-MVA and 5-MCA rose. Microbial analysis indicated that the alpha- and beta-diversity of HRF and MRF groups were lower than LRF's, with different microbial compositions. Transcriptome analysis revealed many differentially expressed genes (DEGs). Compared to MRF, HRF had 348 upregulated and 511 downregulated DEGs. Versus LRF, MRF had 201 upregulated and 185 downregulated DEGs, while HRF had 128 upregulated and 238 downregulated DEGs. Spearman's correlation analysis showed that there was a positive correlation between Butyrivibrio, Quinella, and specific genes. These findings reveal the potential mechanism of rumen flatulence in Xizang sheep and provide new insights into the prevention and treatment of the disease.IMPORTANCEThe research used a high-protein diet to induce a model to understand the diversity of rumen microbiota and its interaction with the host, as well as exploring the molecular mechanisms of rumen flatulence.
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Affiliation(s)
- Jing Wu
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Xiaoming Zhang
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Khan Ayesha
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Shahzad Khuram
- Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad (CUI), Lahore, Pakistan
| | - Jianzhao Cui
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- Shigatse Science Popularization Center, Shigatse, Xizang, China
| | - Gaofu Wang
- Chongqing Academy of Animal Science, Chongqing, China
| | - Zhaxi Yangzong
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
| | - Mingyan Shi
- College of Life Science, Luoyang Normal University, Luoyang, Henan, China
| | - Xunping Jiang
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Long Li
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
| | - Guiqiong Liu
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Wangsheng Zhao
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Tianzeng Song
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
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Frankel G, Findlay M, Bargen L. Treatment-Refractory Epilepsy Alimentary Therapy (TREAT): A canine case study. THE CANADIAN VETERINARY JOURNAL = LA REVUE VETERINAIRE CANADIENNE 2025; 66:378-384. [PMID: 40170936 PMCID: PMC11932361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 04/03/2025]
Abstract
Half of all epilepsy cases in both humans and canines are identified as idiopathic. Of these cases, 30 to 40% remain treatment-refractory to antiepileptic medications. Several human and dog studies have demonstrated low-carbohydrate diets and dietary medium-chain triglyceride (MCT) supplementation are effective for seizure reduction, with some patients achieving a seizure-free status. Recent evidence suggests the gut-brain axis has an important role in the pathology of neurological disease among both humans and dogs. Altered gut microbiota may have a major role in treatment-refractory epilepsy. This case report describes a dog with treatment-refractory epilepsy experiencing cluster seizures triggered by an altered gut microbiome despite therapeutic drug concentrations of multiple agents. Consideration of an underlying gastrointestinal disorder should be investigated in patients with treatment-refractory epilepsy, despite therapeutic concentrations of several antiepileptic medications. Dietary and gastrointestinal health-promoting interventions for epilepsy should also be considered before add-on pharmacotherapy or euthanasia. For difficult epilepsy cases, we suggest exploring the role of a limited-ingredient, low-carbohydrate diet, MCT supplementation, and/or pre/probiotics to augment pharmacotherapeutic strategies. This information may be critically valuable in designing high-quality, diet-based therapies for epileptic dogs. Key clinical message: Gastrointestinal workup, dietary changes to a low-carbohydrate diet, supplementation with MCTs, and addition of pre/probiotics could be considered to augment pharmacotherapeutic strategies in treatmentrefractory epilepsy cases in dogs.
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Affiliation(s)
- Grace Frankel
- Clinical pharmacist, Southern Health, 381 Stonebridge Crossing, Steinbach, Manitoba R5G 0P8 (Frankel); Emergency veterinarian, Pembina Veterinary Hospital, 400 Pembina Hwy, Winnipeg, Manitoba R3L 2E7 (Findlay); Small-animal practice veterinarian, Pet Vet, 25 MB-52A, Steinbach, Manitoba R5G 1X6 (Bargen)
| | - Melissa Findlay
- Clinical pharmacist, Southern Health, 381 Stonebridge Crossing, Steinbach, Manitoba R5G 0P8 (Frankel); Emergency veterinarian, Pembina Veterinary Hospital, 400 Pembina Hwy, Winnipeg, Manitoba R3L 2E7 (Findlay); Small-animal practice veterinarian, Pet Vet, 25 MB-52A, Steinbach, Manitoba R5G 1X6 (Bargen)
| | - Leeanne Bargen
- Clinical pharmacist, Southern Health, 381 Stonebridge Crossing, Steinbach, Manitoba R5G 0P8 (Frankel); Emergency veterinarian, Pembina Veterinary Hospital, 400 Pembina Hwy, Winnipeg, Manitoba R3L 2E7 (Findlay); Small-animal practice veterinarian, Pet Vet, 25 MB-52A, Steinbach, Manitoba R5G 1X6 (Bargen)
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Ma B, Barathan M, Ng MH, Law JX. Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials. Int J Mol Sci 2025; 26:3148. [PMID: 40243936 PMCID: PMC11989138 DOI: 10.3390/ijms26073148] [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: 01/15/2025] [Revised: 03/26/2025] [Accepted: 03/27/2025] [Indexed: 04/18/2025] Open
Abstract
Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development and progression of chronic diseases. This review provides a comprehensive analysis of the complex interplay between these two factors, focusing on how an imbalance between reactive oxygen species (ROS) and antioxidants leads to OS, disrupting cellular homeostasis and contributing to a range of conditions, including metabolic disorders, cardiovascular diseases, neurological diseases, and cancer. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, is essential for regulating immune responses, metabolic pathways, and overall health. Dysbiosis, an imbalance in the gut microbiota composition, is closely associated with chronic inflammation, metabolic dysfunction, and various diseases. This review highlights how the gut microbiota influences and is influenced by OS, complicating the pathophysiology of many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators of cellular crosstalk between the OS and gut microbiota. EVs also play a crucial role in signaling between the gut microbiota and host tissues, modulating immune responses, inflammation, and metabolic processes. The signaling function of EVs holds promise for the development of targeted therapies aimed at restoring microbial balance and mitigating OS. Personalized therapeutic approaches, including probiotics, antioxidants, and fecal microbiota transplantation-based strategies, can be used to address OS-related diseases and improve health outcomes. Nonetheless, further research is needed to study the molecular mechanisms underlying these interactions and the potential of innovative interventions to offer novel strategies for managing OS-related diseases and enhancing overall human health.
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Affiliation(s)
| | | | | | - Jia Xian Law
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (B.M.); (M.B.); (M.H.N.)
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Liu Y, Li X, Chen Y, Yao Q, Zhou J, Wang X, Meng Q, Ji J, Yu Z, Chen X. Fecal microbiota transplantation: application scenarios, efficacy prediction, and factors impacting donor-recipient interplay. Front Microbiol 2025; 16:1556827. [PMID: 40201444 PMCID: PMC11975908 DOI: 10.3389/fmicb.2025.1556827] [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: 01/07/2025] [Accepted: 03/07/2025] [Indexed: 04/10/2025] Open
Abstract
Fecal microbiota transplantation (FMT) represents a therapeutic approach that directly regulates the gut microbiota of recipients, normalizes its composition and reaping therapeutic rewards. Currently, in addition to its general application in treating Clostridium difficile (C. difficile) infection (CDI), FMT treatment has also been extended to the fields of other gastrointestinal diseases, infections, gut-liver or gut-brain axis disorders, metabolic diseases and cancer, etc. Prior to FMT, rigorous donor screening is essential to reduce the occurrence of adverse events. In addition, it is imperative to evaluate whether the recipient can safely and effectively undergo FMT treatment. However, the efficacy of FMT is influenced by the complex interactions between the gut microbiota of donor and recipient, the degree of donor microbiota engraftment is not necessarily positively related with the success rate of FMT. Furthermore, an increasing number of novel factors affecting FMT outcomes are being identified in recent clinical trials and animal experiments, broadening our understanding of FMT treatment. This article provides a comprehensive review of the application scenarios of FMT, the factors influencing the safety and efficacy of FMT from the aspects of both the donors and the recipients, and summarizes how these emerging novel regulatory factors can be combined to predict the clinical outcomes of patients undergoing FMT.
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Affiliation(s)
- Yaxin Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xinru Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Yuchao Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Qinyan Yao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Jinjie Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiaoxuan Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Qingguo Meng
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Jiaxuan Ji
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Zihan Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
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Abdi R, Datta S, Zawar A, Kafle P. Evaluation of extended-spectrum β-lactamase producing bacteria in feces of shelter dogs as a biomarker for altered gut microbial taxa and functional profiles. Front Microbiol 2025; 16:1556442. [PMID: 40196031 PMCID: PMC11975251 DOI: 10.3389/fmicb.2025.1556442] [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: 01/06/2025] [Accepted: 02/19/2025] [Indexed: 04/09/2025] Open
Abstract
Background The USA is home to 83-88 million dogs, with 3-7 million living in shelters. Shelter dogs move through the supply chain from their geographical origin to adoptive homes, with possible exposure to pathogens and shift in their gut microbiota. However, research in this area is limited. This study examined the effects of intestinal colonization by ESBL bacteria on gut taxa abundance, diversity, and functions in 52 shelter dogs of various ages, sexes, and fertility statuses. Methodology We isolated fecal DNA, sequenced their 16S, processed the sequences using DADA2, identified taxa profiles in each dog by Phyloseq, and analyzed Chao1, Shannon, and Simpson alpha diversity by ggplot2 and Wilcoxon test. We analyzed beta diversity using Bray-Curtis dissimilarity matrix from the vegan package. Differential abundance of taxa, gut microbiome functions, and differential abundance of microbiome functions were analyzed using DESeq2, PICRUSt2, and ALDEx2, respectively, with Wilcoxon rank and Kruskal-Wallis tests for comparisons between dog groups. Results Firmicutes (69.3%), Bacteroidota (13.5%), Actinobacteriota (6.77%), Proteobacteria (5.54%), and Fusobacteriota (4.75%) were the major phyla in the gut of shelter dogs. ESBL bacteria colonized dogs had reduced gut microbiota alpha diversity than non-colonized dogs. The abundance levels of the following phyla (Proteobacteria, Deferribacterota, Bacteroidota, Fusobacteriota, and Spirochaetota), class (Gammaproteobacteria, Bacteroidia, Deferribacteres, Brachyspirae, and Fusobacteria), and families (Enterobacteriaceae, Peptostreptococcaceae, Lactobacillaceae, Lachnospiraceae, Prevotellaceae, and Peptostreptococcaceae) were significantly (p < 0.05) varied between the two dog groups. Further stratified analysis by age, sex, and spaying/neutering status influenced the abundance of taxa in ESBL bacteria colonized dogs, indicating these covariates act as effect modifiers. Most gut metabolic and biosynthetic pathways were downregulated in ESBL bacteria colonized dogs compared to non-colonized dogs. However, alpha-linolenic acid metabolism and shigellosis, fluorobenzoate degradation, allantoin degradation, toluene degradation, glycol degradation, fatty acid and beta-oxidation, and glyoxylate metabolism bypass pathways were increased in dogs colonized by ESBL bacteria. Conclusion Colonization by ESBL bacteria marks altered gut microbiota. Dog's demography and fertility status modify the alterations, indicating host factors and ESBL bacteria interplay to shape gut microbiota. ESBL bacteria or other factors reprogram gut microbiome functions through down and upregulating multiple metabolic and biosynthesis pathways to promote ESBL bacteria colonization.
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Affiliation(s)
- Reta Abdi
- Biomedical Sciences College of Veterinary Medicine, Long Island University, Brookville, NY, United States
| | - Srinka Datta
- GeneSpectrum Life Sciences LLP, Pune, Maharashtra, India
| | | | - Pratap Kafle
- Shreiber School of Veterinary Medicine, Rowan University, Mullica Hill, NJ, United States
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Zhra M, Elahi MA, Tariq A, Abu-Zaid A, Yaqinuddin A. Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma. Cells 2025; 14:466. [PMID: 40136715 PMCID: PMC11941559 DOI: 10.3390/cells14060466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/12/2025] [Accepted: 03/13/2025] [Indexed: 03/27/2025] Open
Abstract
Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The gut microbiome interacts with the liver via a bidirectional relationship with the gut-liver axis. Microbial metabolites, sirtuins, and immune responses are pivotal in different metabolic diseases. This extensive review explores the complex and multifaceted interrelationship between sirtuins and gut microbiota, highlighting their importance in health and disease, particularly metabolic dysfunction and hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as a group of NAD+-dependent deacetylases, serve as crucial modulators of a wide spectrum of cellular functions, including metabolic pathways, the inflammatory response, and the process of senescence. Their subcellular localization and diverse functions link them to various health conditions, including NAFLD and cancer. Concurrently, the gut microbiota, comprising diverse microorganisms, significantly influences host metabolism and immune responses. Recent findings indicate that sirtuins modulate gut microbiota composition and function, while the microbiota can affect sirtuin activity. This bidirectional relationship is particularly relevant in metabolic disorders, where dysbiosis contributes to disease progression. The review highlights recent findings on the roles of specific sirtuins in maintaining gut health and their implications in metabolic dysfunction and HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked to metabolic dysregulation and liver pathology.
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Affiliation(s)
- Mahmoud Zhra
- Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
| | - Muhammad Affan Elahi
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.A.E.); (A.A.-Z.)
| | - Aamira Tariq
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Islamabad 45550, Pakistan
| | - Ahmed Abu-Zaid
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.A.E.); (A.A.-Z.)
| | - Ahmed Yaqinuddin
- Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
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Jha SS, Jeyaraman N, Jeyaraman M, Ramasubramanian S, Muthu S, Santos GS, da Fonseca LF, Lana JF. Cross-talks between osteoporosis and gut microbiome. World J Orthop 2025; 16:102274. [PMID: 40124724 PMCID: PMC11924030 DOI: 10.5312/wjo.v16.i3.102274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/06/2025] [Accepted: 02/06/2025] [Indexed: 03/12/2025] Open
Abstract
The gut microbiome comprises a vast community of microbes inhabiting the human alimentary canal, playing a crucial role in various physiological functions. These microbes generally live in harmony with the host; however, when dysbiosis occurs, it can contribute to the pathogenesis of diseases, including osteoporosis. Osteoporosis, a systemic skeletal disease characterized by reduced bone mass and increased fracture risk, has attracted significant research attention concerning the role of gut microbes in its development. Advances in molecular biology have highlighted the influence of gut microbiota on osteoporosis through mechanisms involving immunoregulation, modulation of the gut-brain axis, and regulation of the intestinal barrier and nutrient absorption. These microbes can enhance bone mass by inhibiting osteoclast differentiation, inducing apoptosis, reducing bone resorption, and promoting osteoblast proliferation and maturation. Despite these promising findings, the therapeutic effectiveness of targeting gut microbes in osteoporosis requires further investigation. Notably, gut microbiota has been increasingly studied for their potential in early diagnosis, intervention, and as an adjunct therapy for osteoporosis, suggesting a growing utility in improving bone health. Further research is essential to fully elucidate the therapeutic potential and clinical application of gut microbiome modulation in the management of osteoporosis.
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Affiliation(s)
- Shiva Shankar Jha
- Department of Orthopaedics, Harishchandra Orthopaedic Research Institute, Patna 880023, Bihar, India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Sathish Muthu
- Department of Orthopaedics, Government Medical College and Hospital, Karur 639004, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| | - Gabriel Silva Santos
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
| | - Lucas Furtado da Fonseca
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
| | - José Fábio Lana
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
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