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Sahebi K, Arianejad M, Azadi S, Hosseinpour-Soleimani F, Kazemi R, Tajbakhsh A, Negahdaripour M. The interplay between gut microbiome, epigenetics, and substance use disorders: from molecular to clinical perspectives. Eur J Pharmacol 2025; 998:177630. [PMID: 40252900 DOI: 10.1016/j.ejphar.2025.177630] [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: 12/26/2024] [Revised: 03/27/2025] [Accepted: 04/15/2025] [Indexed: 04/21/2025]
Abstract
Substance use disorders (SUDs) involve a complex series of central and peripheral pathologies, leading to impairments in cognitive, behavioral, and physiological processes. Emerging evidence indicates a more significant role for the microbiome-gut-brain axis (MGBA) in SUDs than previously recognized. The MGBA is interconnected with various body systems by producing numerous metabolites, most importantly short-chain fatty acids (SCFAs), cytokines, and neurotransmitters. These mediators influence the human body's epigenome and transcriptome. While numerous epigenetic alterations in different brain regions have been reported in SUD models, the intricate relationship between SUDs and the MGBA suggests that the gut microbiome may partially contribute to the underlying mechanisms of SUDs. Promising results have been observed with gut microbiome-directed interventions in patients with SUDs, including prebiotics, probiotics, antibiotics, and fecal microbiota transplantation. Nonetheless, the long-term epigenetic effects of these interventions remain unexplored. Moreover, various confounding factors and study limitations have hindered the identification of molecular mechanisms and clinical applications of gut microbiome interventions in SUDs. In the present review, we will (i) provide a comprehensive discussion on how the gut microbiome influences SUDs, with an emphasis on epigenetic alterations; (ii) discuss the current evidence on the bidirectional relationship of gut microbiome and SUDs, highlighting potential targets for intervention; and (iii) review recent advances in gut microbiome-directed therapies, along with their limitations and future directions.
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Affiliation(s)
- Keivan Sahebi
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mona Arianejad
- Department of Molecular Medicine, School of Advanced Technologies of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Soha Azadi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Hosseinpour-Soleimani
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Applied Cell Sciences and Tissue Engineering, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Radmehr Kazemi
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Manica Negahdaripour
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
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Horn JA, Delgadillo DR, Mayer EA. Understanding Microbial Mediation of the Brain-Gut Axis. Gastroenterol Clin North Am 2025; 54:367-381. [PMID: 40348493 DOI: 10.1016/j.gtc.2024.12.004] [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] [Indexed: 05/14/2025]
Abstract
Bidirectional communications between the gut and the brain play an important role in the regulation of food intake, pain perception, mood, and cognitive function. The involved communication pathways are modulated by signals generated by the gut microbiome. Alterations in these communications have been implicated in several chronic brain and gut disorders, including food addiction, mood disorders, neurodevelopmental and neurodegenerative disorders, and functional and inflammatory bowel disorders. The gut microbiome holds great promise for the development of novel therapies normalizing altered brain-gut interactions.
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Affiliation(s)
- Jill A Horn
- Department of Population and Public Health Sciences, Keck School of Medicine at USC, 1845 N Soto Street, Los Angeles, CA 90032, USA
| | - Desiree R Delgadillo
- Goodman-Luskin Microbiome Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS 42-210, MC737818, Los Angeles, CA 90095-73787, USA
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress & Resilience; UCLA Vatche & Tamar Manoukian Division of Digestive Diseases, Goodman Luskin Microbiome Center, UCLA.
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Oliver PJ, Civitelli L, Hu MT. The gut-brain axis in early Parkinson's disease: from prodrome to prevention. J Neurol 2025; 272:413. [PMID: 40394204 DOI: 10.1007/s00415-025-13138-5] [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: 03/07/2025] [Revised: 04/28/2025] [Accepted: 04/30/2025] [Indexed: 05/22/2025]
Abstract
Parkinson's disease is the second most common neurodegenerative disorder and fastest growing neurological condition worldwide, yet its etiology and progression remain poorly understood. This disorder is characterized pathologically by the prion-like spread of misfolded neuronal alpha-synuclein proteins in specific brain regions leading to Lewy body formation, neurodegeneration, and progressive neurological impairment. It is unclear what triggers Parkinson's and where α-synuclein protein aggregation begins, although proposed induction sites include the olfactory bulb and dorsal motor nucleus of the vagus nerve. Within the last 20 years, there has been increasing evidence that Parkinson's could be triggered by early microbiome changes and α-synuclein accumulation in the gastrointestinal system. Gut microbiota dysbiosis that alters gastrointestinal motility, permeability, and inflammation could enable prion-like spread of α-synuclein from the gut-to-brain via the enteric nervous system. Individuals with isolated rapid eye movement sleep behavior disorder have a high likelihood of developing Parkinson's and might represent a prodromal 'gut-first' subtype of the condition. The gut-first model of Parkinson's offers novel gut-based therapeutic avenues, such as anti-, pre-, and pro-biotic preparations and fecal microbiota transplants. Crucially, gut-based interventions offer an avenue to treat Parkinson's at early prodromal stages with the aim of mitigating evolution to clinically recognizable Parkinson's disease characterized by motor impairment.
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Affiliation(s)
- Patrick James Oliver
- Clinical Medical School, University of Oxford, Oxford, UK
- Green Templeton College, University of Oxford, Oxford, UK
| | - Livia Civitelli
- Nuffield Department of Clinical Neurosciences, Oxford Parkinsons' Disease Center, University of Oxford, Oxford, UK
| | - Michele T Hu
- Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
- Department of Neurology, West Wing, Level 3, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
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Chen Z, Zhang Z, Nie BN, Huang W, Zhu Y, Zhang L, Xu M, Wang M, Yuan C, Liu N, Wang X, Tian J, Ba Q, Wang Z. Temporal network analysis of gut microbiota unveils aging trajectories associated with colon cancer. mSystems 2025; 10:e0118824. [PMID: 40298386 PMCID: PMC12090783 DOI: 10.1128/msystems.01188-24] [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: 08/31/2024] [Accepted: 03/24/2025] [Indexed: 04/30/2025] Open
Abstract
The human gut microbiome's role in colorectal cancer (CRC) pathogenesis has gained increasing recognition. This study aimed to delineate the microbiome characteristics that distinguish CRC patients from healthy individuals, while also evaluating the influence of aging, through a comprehensive metagenomic approach. The study analyzed a cohort of 80 CRC patients and 80 matched healthy controls, dividing participants into a normal and a CRC group, further categorized by age into young, middle-aged, and old-aged subgroups. Extensive metagenomic sequencing of fecal samples allowed for the exploration of both the structural and functional profiles of the microbiome, with findings validated in an independent cohort to ensure robustness. Our results highlight notable differences in microbiome composition between CRC patients and healthy individuals, which exhibit age-dependent variations. Specifically, a higher prevalence of pathogenic bacteria, such as Bacteroides vulgatus, known to drive inflammation and carcinogenesis, was observed in CRC patients, alongside a reduction in beneficial microbes, including Lactobacillus. Functionally, the CRC-associated microbiome showed an increase in pathways related to DNA repair, cell cycle regulation, and metabolic activities, such as the Citrate cycle and Galactose metabolism, underscoring distinct microbial alterations in CRC patients that could influence disease onset and progression. These insights lay a foundation for future research into microbiome-based diagnostics and treatments for CRC. IMPORTANCE This study underscores the critical role of the gut microbiome in colorectal cancer (CRC) pathogenesis, particularly in the context of aging. By identifying age-specific microbial biomarkers and functional pathways associated with CRC, our findings provide novel insights into how microbiome composition and metabolic activities influence disease progression. These discoveries pave the way for developing personalized microbiome-based diagnostic tools and therapeutic strategies, potentially improving CRC prevention and treatment outcomes across different age groups. Understanding these microbial dynamics could also inform interventions targeting gut microbiota to mitigate CRC risk and progression.
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Affiliation(s)
- Ziqi Chen
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhipeng Zhang
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Bei Ning Nie
- Nanjing University of Traditional Chinese Medicine, Nanjing, China
| | - Wei Huang
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ying Zhu
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Long Zhang
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Meng Xu
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengfei Wang
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chenyue Yuan
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ningning Liu
- State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinyi Wang
- Department of Pathology, University of California, San Diego, La Jolla, California, USA
| | - Jianhui Tian
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qian Ba
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ziliang Wang
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Ye H, Meehan D, Timmons S, O'Toole PW. Effects of Prebiotics and a Synthetic Microbiome Consortium on the Composition and Metabolites of the Elderly Gut Microbiota In Vitro. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:11720-11729. [PMID: 40324006 DOI: 10.1021/acs.jafc.5c00364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
A 24 h artificial colon fermentation was performed to assess the effects of a prebiotic MIX and synthetic consortium (S7) on gut microbiota composition and microbial metabolite production in clinically stratified older adults (healthy and frail). Treatments included supplementation of the donor microbiota with a synthetic microbial consortium (S7), a prebiotic mix (MIX), and a combination of MIX and S7 (MIX+S7). The S7 treatment decreased the alpha diversity of long-stay-dwelling donor (LS, "frail") microbiota and increased the relative abundance of S7 taxa at 16 h. MIX alone caused the enrichment of reportedly beneficial genera such as Coprobacillus and Eubacterium in community-dwelling donor (CM, "healthy") microbiota and Citrobacter and Faecalibacterium in LS microbiota. The MIX+S7 treatment sustained higher overall S7 species richness and consortium taxon abundance at 24 h. Both MIX and MIX+S7 treatments enhanced short-chain acid production compared to control. These findings highlight the differential responses of microbiota from distinct elderly health strata to prebiotic and microbial consortia supplementation.
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Affiliation(s)
- Huimin Ye
- School of Microbiology, and APC Microbiome Ireland, University College Cork, Western Road, T12 Y337 Cork, Ireland
| | - Dara Meehan
- School of Microbiology, and APC Microbiome Ireland, University College Cork, Western Road, T12 Y337 Cork, Ireland
| | - Suzanne Timmons
- Centre for Gerontology and Rehabilitation, School of Medicine, University College Cork, Western Road, T12 Y337 Cork, Ireland
| | - Paul W O'Toole
- School of Microbiology, and APC Microbiome Ireland, University College Cork, Western Road, T12 Y337 Cork, Ireland
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Fernandez E, Wargo JA, Helmink BA. The Microbiome and Cancer: A Translational Science Review. JAMA 2025:2833859. [PMID: 40354071 DOI: 10.1001/jama.2025.2191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Importance Growing evidence suggests that microbes located within the gastrointestinal tract and other anatomical locations influence the development and progression of diseases such as cancer. Observations Clinical and preclinical evidence suggests that microbes in the gastrointestinal tract and other anatomical locations, such as the respiratory tract, may affect carcinogenesis, development of metastases, cancer treatment response, and cancer treatment-related adverse effects. Within tumors of patients with cancer, microbes may affect response to treatment, and therapies that reduce or eliminate these microbes may improve outcomes in patients with cancer. Modulating gastrointestinal tract (gut) microbes through fecal microbiota transplant and other strategies such as dietary intervention (eg, high-fiber diet intervention) has improved outcomes in small studies of patients treated with cancer immunotherapy. In contrast, disruption of the gut microbiota by receipt of broad-spectrum antibiotics prior to treatment with cancer immunotherapy has been associated with poorer overall survival and higher rates of adverse effects in patients treated with immune checkpoint blockade for solid tumors and also with chimeric antigen receptor T-cell therapy for hematologic malignancies. Conclusions and Relevance Microbes in the gut and other locations in the body may influence the development and progression of cancer and may affect the response to adverse effects from cancer therapy. Future therapies targeting microbes in the gut and other locations in the body could potentially improve outcomes in patients with cancer.
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Affiliation(s)
- Estefania Fernandez
- Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston
| | - Jennifer A Wargo
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston
| | - Beth A Helmink
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
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Zeng H, Liu C, Wan L, Peng L, Wang K, Zhou F, Fang W, Wen S, Bai Q, Yang X, Liu L, Zeng J, Huang J, Liu Z. Epigallocatechin gallate prevents and alleviates type 2 diabetes mellitus (T2DM) through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats. J Adv Res 2025:S2090-1232(25)00296-6. [PMID: 40349958 DOI: 10.1016/j.jare.2025.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/21/2025] [Accepted: 05/02/2025] [Indexed: 05/14/2025] Open
Abstract
INTRODUCTION As the main active ingredient of the first FDA-approved phytochemical drug, epigallocatechin gallate (EGCG) can effectively alleviate glucolipid metabolic disorders. However, existing studies mainly focuses on the treatment of EGCG in disease models, with limited focus on its preventive effect on diseases in healthy models. OBJECTIVES This study investigated how EGCG prevents and alleviates T2DM through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats. METHODS The GK T2DM rat strain was established through repeated selective breeding of Wistar rats with glucose intolerance. Whether and how EGCG prevents and alleviates T2DM were evaluated, including glucose production and absorption efficiency, glucose transport, glucose metabolism, glucose excretion, T2DM-related tissue damage, gut microbiota, and liver transcriptome. RESULTS The health benefits of EGCG are primarily reliant on the involvement of the gut microbiota. Our study showed that although the specific microbial communities involved differ, the bidirectional interaction between EGCG and gut microbiota is widespread in healthy rats and T2DM rats. EGCG intervention elevated the relative abundance of specific microbial communities, which in turn promoted the metabolic processing of EGCG in the gut, producing numerous EGCG metabolites that may contribute to preventing and alleviating T2DM. In healthy rats, EGCG intervention selectively enhanced insulin secretion and serum insulin levels to prevent T2DM. In T2DM rats, EGCG intervention selectively lowered blood glucose levels, improved insulin resistance, delayed glucose production and absorption, and promoted urinary glucose excretion to alleviate T2DM. In both healthy and T2DM rats, EGCG intervention universally reduced gut microbiota-derived lipopolysaccharides, maintained systemic oxidative stress homeostasis, alleviated liver and kidney damage, increased muscle glycogen content, and promoted beige thermogenesis in white fat, thus demonstrating potential for preventing and alleviating T2DM. CONCLUSION As a natural active ingredient, EGCG could prevent and alleviate T2DM through gut microbiota and multi-organ interactions.
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Affiliation(s)
- Hongzhe Zeng
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Changwei Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Liwei Wan
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Liyuan Peng
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Kuofei Wang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Fang Zhou
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Wenwen Fang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Shuai Wen
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Qixian Bai
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Xiaomei Yang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Linmei Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China
| | - Jie Zeng
- Micangshan Tea Industry Research Institute, Sichuan Wangcang Vocational Middle School, Sichuan 628200, China
| | - Jian'an Huang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China.
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China; National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Changsha 410128, China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, China.
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8
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Metris A, Walker AW, Showering A, Doolan A, McBain AJ, Ampatzoglou A, Murphy B, O'Neill C, Shortt C, Darby EM, Aldis G, Hillebrand GG, Brown HL, Browne HP, Tiesman JP, Leng J, Lahti L, Jakubovics NS, Hasselwander O, Finn RD, Klamert S, Korcsmaros T, Hall LJ. Assessing the safety of microbiome perturbations. Microb Genom 2025; 11. [PMID: 40371892 DOI: 10.1099/mgen.0.001405] [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] [Indexed: 05/16/2025] Open
Abstract
Everyday actions such as eating, tooth brushing or applying cosmetics inherently modulate our microbiome. Advances in sequencing technologies now facilitate detailed microbial profiling, driving intentional microbiome-targeted product development. Inspired by an academic-industry workshop held in January 2024, this review explores the oral, skin and gut microbiomes, focussing on the potential long-term implications of perturbations. Key challenges in microbiome safety assessment include confounding factors (ecological variability, host influences and external conditions like geography and diet) and biases from experimental measurements and bioinformatics analyses. The taxonomic composition of the microbiome has been associated with both health and disease, and perturbations like regular disruption of the dental biofilm are essential for preventing caries and inflammatory gum disease. However, further research is required to understand the potential long-term impacts of microbiome disturbances, particularly in vulnerable populations including infants. We propose that emerging technologies, such as omics technologies to characterize microbiome functions rather than taxa, leveraging artificial intelligence to interpret clinical study data and in vitro models to characterize and measure host-microbiome interaction endpoints, could all enhance the risk assessments. The workshop emphasized the importance of detailed documentation, transparency and openness in computational models to reduce uncertainties. Harmonisation of methods could help bridge regulatory gaps and streamline safety assessments but should remain flexible enough to allow innovation and technological advancements. Continued scientific collaboration and public engagement are critical for long-term microbiome monitoring, which is essential to advancing safety assessments of microbiome perturbations.
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Affiliation(s)
- Aline Metris
- Unilever, Safety, Environmental and Regulatory Sciences (SERS), Sharnbrook, UK
| | - Alan W Walker
- Microbiome, Food Innovation and Food Security Theme, Rowett Institute, University of Aberdeen, Aberdeen, UK
| | | | | | - Andrew J McBain
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Antonis Ampatzoglou
- Unilever, Safety, Environmental and Regulatory Sciences (SERS), Sharnbrook, UK
| | - Barry Murphy
- Unilever R&D Port Sunlight, Bebington, Wirral, UK
| | - Catherine O'Neill
- Division of Dermatology and Musculoskeletal Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | | | - Elizabeth M Darby
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | | | - Greg G Hillebrand
- University of Cincinnati, James L. Winkle College of Pharmacy, Cincinnati, OH, USA
| | - Helen L Brown
- School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK
| | - Hilary P Browne
- School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College, Cork, Ireland
| | | | - Joy Leng
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Leo Lahti
- Department of Computing, University of Turku, Turku FI-20014, Finland
| | - Nicholas S Jakubovics
- School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | | | - Robert D Finn
- European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK
| | - Silvia Klamert
- Unilever, Safety, Environmental and Regulatory Sciences (SERS), Sharnbrook, UK
| | - Tamas Korcsmaros
- Food, Microbiomes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
- Division of Digestive Diseases, Imperial College London, London, UK
- NIHR Imperial BRC Organoid Facility, Imperial College London, London, UK
| | - Lindsay J Hall
- Food, Microbiomes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
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9
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Yang K, Li G, Li Q, Wang W, Zhao X, Shao N, Qiu H, Liu J, Xu L, Zhao J. Distribution of gut microbiota across intestinal segments and their impact on human physiological and pathological processes. Cell Biosci 2025; 15:47. [PMID: 40241220 PMCID: PMC12001467 DOI: 10.1186/s13578-025-01385-y] [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: 01/13/2025] [Accepted: 03/25/2025] [Indexed: 04/18/2025] Open
Abstract
In recent years, advancements in metagenomics, metabolomics, and single-cell sequencing have enhanced our understanding of the intricate relationships between gut microbiota and their hosts. Gut microbiota colonize humans from birth, with their initial composition significantly influenced by the mode of delivery and feeding method. During the transition from infancy to early childhood, exposure to a diverse diet and the maturation of the immune system lead to the gradual stabilization of gut microbiota's composition and distribution. Numerous studies have demonstrated that gut microbiota can influence a wide range of physiological functions and pathological processes by interacting with various tissues and organs through the gut-organ axis. Different intestinal segments exhibit unique physical and chemical conditions, which leads to the formation of vertical gradients along the intestinal tract: aerobes and facultative aerobes mainly live in the small intestine and anaerobic bacteria mainly live in the large intestine, and horizontal gradients: mucosa-associated microbiota and lumen-associated microbiota. In this review, we systematically summarize the distribution characteristics of gut microbiota across six intestinal segments: duodenum, jejunum, ileum, cecum, colon, and rectum. We also draw a conclusion that gut microbiota distributed in different intestinal segments affect the progression of different diseases. We hope to elucidate the role of microbiota at specific anatomic sites within the gut in precisely regulating the processes of particular diseases, thereby providing a solid foundation for developing novel diagnostic and therapeutic strategies for related diseases.
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Affiliation(s)
- Ke Yang
- The First Clinical Institute, Zunyi Medical University, Zunyi, 563000, China
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Guangqin Li
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Qihong Li
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Wei Wang
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Xu Zhao
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
- Guizhou University Medical College, Guiyang, 550025, Guizhou, China
| | - Nan Shao
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Hui Qiu
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Jing Liu
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Lin Xu
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China.
- Department of Immunology, Zunyi Medical University, Zunyi, 563000, Guizhou, China.
| | - Juanjuan Zhao
- Key Laboratory for Cancer Prevention and treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, Guizhou, China.
- Department of Immunology, Zunyi Medical University, Zunyi, 563000, Guizhou, China.
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10
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Gilbert JA, Azad MB, Bäckhed F, Blaser MJ, Byndloss M, Chiu CY, Chu H, Dugas LR, Elinav E, Gibbons SM, Gilbert KE, Henn MR, Ishaq SL, Ley RE, Lynch SV, Segal E, Spector TD, Strandwitz P, Suez J, Tropini C, Whiteson K, Knight R. Clinical translation of microbiome research. Nat Med 2025; 31:1099-1113. [PMID: 40217076 DOI: 10.1038/s41591-025-03615-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 02/26/2025] [Indexed: 04/18/2025]
Abstract
The landscape of clinical microbiome research has dramatically evolved over the past decade. By leveraging in vivo and in vitro experimentation, multiomic approaches and computational biology, we have uncovered mechanisms of action and microbial metrics of association and identified effective ways to modify the microbiome in many diseases and treatment modalities. This Review explores recent advances in the clinical application of microbiome research over the past 5 years, while acknowledging existing barriers and highlighting opportunities. We focus on the translation of microbiome research into clinical practice, spearheaded by Food and Drug Administration (FDA)-approved microbiome therapies for recurrent Clostridioides difficile infections and the emerging fields of microbiome-based diagnostics and therapeutics. We highlight key examples of studies demonstrating how microbiome mechanisms, metrics and modifiers can advance clinical practice. We also discuss forward-looking perspectives on key challenges and opportunities toward integrating microbiome data into routine clinical practice, precision medicine and personalized healthcare and nutrition.
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Affiliation(s)
- Jack A Gilbert
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA.
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
| | - Meghan B Azad
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
- Manitoba Interdisciplinary Lactation Centre, Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada
- CIFAR Humans & the Microbiome Program, CIFAR, Toronto, Ontario, Canada
| | - Fredrik Bäckhed
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Martin J Blaser
- CIFAR Humans & the Microbiome Program, CIFAR, Toronto, Ontario, Canada
- Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA
| | - Mariana Byndloss
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Charles Y Chiu
- Department of Laboratory Medicine, University of California, San Fransisco, San Francisco, CA, USA
- Department of Medicine, Division of Infectious Diseases, University of California, San Fransisco, San Francisco, CA, USA
- Chan-Zuckerberg Biohub, San Francisco, CA, USA
| | - Hiutung Chu
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Pathology, University of California San Diego, La Jolla, CA, USA
- Chiba University-UC San Diego Center for Mucosal Immunology, Allergy and Vaccines, La Jolla, CA, USA
| | - Lara R Dugas
- Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA
- Division of Epidemiology and Biostatistics, School of Public Health, University of Cape Town, Cape Town, South Africa
| | - Eran Elinav
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel
- Microbiome and Cancer Division, DKFZ, Heidelberg, Germany
| | - Sean M Gibbons
- Institute for Systems Biology, Seattle, WA, USA
- Department of Bioengineering, University of Washington, Seattle, WA, USA
- Department of Genome Sciences, University of Washington, Seattle, WA, USA
- eScience Institute, University of Washington, Seattle, WA, USA
| | - Katharine E Gilbert
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | | | - Suzanne L Ishaq
- School of Food and Agriculture, University of Maine, Orono, ME, USA
- Microbes and Social Equity working group, Orono, ME, USA
| | - Ruth E Ley
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Susan V Lynch
- Benioff Center for Microbiome Medicine, Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Eran Segal
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
| | - Tim D Spector
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
- ZOE Ltd, London, UK
| | | | - Jotham Suez
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Carolina Tropini
- CIFAR Humans & the Microbiome Program, CIFAR, Toronto, Ontario, Canada
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - Katrine Whiteson
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA
- Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, San Diego, CA, USA
- Halıcıoğlu Data Science Institute, University of California San Diego, San Diego, CA, USA
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11
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Tahiri M, Gilbert JA. Examining the potential prebiotic effect of almonds. J Appl Microbiol 2025; 136:lxaf078. [PMID: 40156575 DOI: 10.1093/jambio/lxaf078] [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: 01/30/2025] [Revised: 03/19/2025] [Accepted: 03/27/2025] [Indexed: 04/01/2025]
Abstract
Almonds, a nutrient-dense food rich in dietary fiber, polyphenols, and unsaturated fatty acids, exhibit significant potential as a functional food with prebiotic effects. Prebiotics selectively stimulate the growth and activity of beneficial gut microbiota, leading to improved gut and systemic health. This review synthesizes evidence from in vitro studies, clinical trials, and systematic reviews to elucidate the prebiotic effects of almond consumption. Almonds enhance gut microbiota diversity and composition, particularly increasing beneficial bacteria such as Bifidobacterium and Roseburia, while promoting the production of short-chain fatty acids (SCFAs), such as butyrate, which are critical for gut barrier integrity and inflammation modulation. The presence of polyphenols, such as proanthocyanidins, contributes to their antioxidative and antimicrobial properties, further supporting microbiome health. Despite variability in study outcomes, likely due to differences in population health status, study design, and almond preparation methods, the cumulative findings underscore almonds' role as a potential prebiotic food with the potential to improve cardiovascular health. Continued research focusing on individualized responses and standardized methodologies is essential to fully harness the health benefits of almond consumption.
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Affiliation(s)
- Maha Tahiri
- Nutrition Sustainability Strategies, St Petersburg, FL 33702, United States
- Tufts University, Friedmann School of Nutrition Science and Policy, Boston, MA 02111, United States
| | - Jack A Gilbert
- Department of Pediatrics, University of California San Diego, La Jolla, CA 92023, United States
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92023, United States
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA 92023, United States
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12
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Zhang Y, Wang L, Peng L. The Role of Intestinal Fungi in the Pathogenesis and Treatment of Ulcerative Colitis. Microorganisms 2025; 13:794. [PMID: 40284630 PMCID: PMC12029736 DOI: 10.3390/microorganisms13040794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/27/2025] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely associated with dysbiosis of the gut microbiome, encompassing not only bacterial communities but also fungal populations. Despite the growing recognition of the gut microbiome's role in UC pathogenesis, the contribution of intestinal fungi has only recently garnered significant attention. In this review, we comprehensively examine the characteristics of intestinal fungi in both healthy individuals and UC patients, elucidating their role in disease pathogenesis and their interactions with bacterial communities. Additionally, we explore the impact of intestinal fungi on disease severity and therapeutic responses in UC. Furthermore, we evaluate the therapeutic potential of antifungal agents, probiotics, and fecal microbiota transplantation (FMT) in UC management, emphasizing the critical role of fungi in these treatment modalities. Future research should prioritize elucidating the multifunctional roles of fungi in UC pathogenesis and their implications for treatment strategies. Moreover, the identification of fungal biomarkers associated with FMT efficacy could pave the way for precision medicine approaches in FMT, offering novel insights into personalized therapeutic interventions for UC.
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Affiliation(s)
- Yujing Zhang
- Microbiota Laboratory, Clinical Division of Microbiota, Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; (Y.Z.); (L.W.)
- Medical School of Chinese PLA, Beijing 100853, China
| | - Lin Wang
- Microbiota Laboratory, Clinical Division of Microbiota, Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; (Y.Z.); (L.W.)
- Medical School of Chinese PLA, Beijing 100853, China
| | - Lihua Peng
- Microbiota Laboratory, Clinical Division of Microbiota, Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; (Y.Z.); (L.W.)
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13
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Goel A, Shete O, Goswami S, Samal A, C B L, Kedia S, Ahuja V, O'Toole PW, Shanahan F, Ghosh TS. Toward a health-associated core keystone index for the human gut microbiome. Cell Rep 2025; 44:115378. [PMID: 40023840 DOI: 10.1016/j.celrep.2025.115378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 11/19/2024] [Accepted: 02/10/2025] [Indexed: 03/04/2025] Open
Abstract
A robust index of gut microbiome taxa encompassing their association with host health and microbiome resilience would be valuable for development and optimization of microbiome-based therapeutics. Here we present a single ranked order for 201 taxa, the Health-Associated Core Keystone (HACK) index, derived using their association strengths with prevalence/community association in non-diseased subjects, longitudinal stability, and host health. The index was derived based on 127 discovery cohorts and 14 validation datasets (cumulatively encompassing 45,424 gut microbiomes, subject age >18 years, representing 42 countries, 28 disease categories, and 10,021 longitudinal samples). We show that this index is reproducible regardless of microbiome profiling strategies and cohort lifestyle. Specific consortia of high HACK index taxa respond positively to Mediterranean diet interventions and reflect immune checkpoint inhibitor responsiveness and associated with specific functional profiles at the genome level. The availability of HACK indices provides a rational basis for comparing microbiomes and facilitating selection and design of microbiome-based therapeutics.
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Affiliation(s)
- Abhishek Goel
- Department of Computational Biology, Indraprastha Institute of Information Technology (IIIT-Delhi), Okhla Phase III, New Delhi, India
| | - Omprakash Shete
- Department of Computational Biology, Indraprastha Institute of Information Technology (IIIT-Delhi), Okhla Phase III, New Delhi, India
| | - Sourav Goswami
- Department of Computational Biology, Indraprastha Institute of Information Technology (IIIT-Delhi), Okhla Phase III, New Delhi, India
| | - Amit Samal
- Department of Computational Biology, Indraprastha Institute of Information Technology (IIIT-Delhi), Okhla Phase III, New Delhi, India
| | - Lavanya C B
- Department of Computational Biology, Indraprastha Institute of Information Technology (IIIT-Delhi), Okhla Phase III, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Paul W O'Toole
- Schools of Microbiology and Medicine, & APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Fergus Shanahan
- Schools of Microbiology and Medicine, & APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Tarini Shankar Ghosh
- Department of Computational Biology, Indraprastha Institute of Information Technology (IIIT-Delhi), Okhla Phase III, New Delhi, India.
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14
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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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15
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Frame LA. Fiber, microbiomes, and SCFAs: insights from companion animal models to inform personalized nutrition. mSystems 2025; 10:e0145424. [PMID: 39927761 PMCID: PMC11915871 DOI: 10.1128/msystems.01454-24] [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] [Indexed: 02/11/2025] Open
Abstract
A recent study by A. Bhosle, M. I. Jackson, A. M. Walsh, E. A. Franzosa, et al. (mSystems 10:e00452-24, 2024, https://doi.org/10.1128/msystems.00452-24) enhances our understanding of dietary fiber's impact on the gut microbiome and metabolome in companion animals, uncovering individual variations in microbial and metabolic responses. By examining short-chain fatty acid (SCFA) profiles in response to fiber, the authors reveal potential therapeutic benefits of tailored dietary interventions, such as enhanced gut and immune health. These findings resonate with human microbiome research, where dietary fiber has shown health benefits through microbial diversity and SCFA production. The study emphasizes the potential for breed-specific responses to fiber, given the variation in microbiome composition and physiology across breeds. Such insights align with emerging concepts of personalized nutrition, offering an opportunity to develop precision dietary strategies that address specific health needs in both veterinary and human contexts. This foundational research positions dietary fiber as a valuable tool in preventive health, providing a roadmap for future studies to refine individualized approaches for gut microbiome modulation.
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Affiliation(s)
- Leigh A. Frame
- The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Resiliency & Well-being Center, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Office of Integrative Medicine and Health, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Department of Physician Assistant Studies, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
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16
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Li C, Cheng D, Ren H, Zhang T. Unraveling the gut microbiota's role in PCOS: a new frontier in metabolic health. Front Endocrinol (Lausanne) 2025; 16:1529703. [PMID: 40171188 PMCID: PMC11958223 DOI: 10.3389/fendo.2025.1529703] [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: 11/17/2024] [Accepted: 02/27/2025] [Indexed: 04/03/2025] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting reproductive-age women, characterized primarily by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. In recent years, the gut microbiota has garnered widespread attention for its potential role as a key regulator of host metabolism in the pathogenesis of PCOS. Studies have shown that PCOS patients exhibit dysbiosis in their gut microbiota, characterized by reduced microbial diversity, an imbalance in the ratio of Firmicutes to Bacteroidetes, changes in the abundance of specific taxa, and abnormal levels of metabolic products. These alterations may exacerbate metabolic dysfunction in PCOS through multiple mechanisms, including influencing host energy metabolism, disrupting lipid and bile acid metabolism, and inducing chronic inflammation. Addressing gut dysbiosis through the modulation of patients' microbiomes-such the use of, prebiotics, fecal microbiota transplantation, and optimizing diet lifestyle-may offer strategies for improving metabolic abnormalities and alleviating clinical symptoms in PCOS. Additionally, the gut microbiome promises as a potential marker, aiding in the precise diagnosis and personalization of PCOS. Although our current understanding of how the gut microbiota influences PCOS is still limited, research is needed to explore the causal relationships and mechanisms involved, providing a more reliable theoretical basis for clinical. This review aims summarize the research progress on the relationship between gut microbiota and PCOS, and to suggest future directions to promote the development of prevention and treatment strategies for PCOS.
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Affiliation(s)
- Caihong Li
- Department of Assisted Reproductive Laboratory, Shenyang Jinghua Hospital, Shenyang, China
| | - Dongkai Cheng
- Department of Assisted Reproductive Laboratory, Shenyang Jinghua Hospital, Shenyang, China
| | - Haiqin Ren
- Department of Assisted Reproductive Laboratory, Shenyang Jinghua Hospital, Shenyang, China
| | - Tao Zhang
- Department of Stem Cells and Regenerative Medicine, Shenyang Key Laboratory of Stem Cell and Regenerative Medicine, China Medical University, Shenyang, China
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17
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Safarchi A, Al-Qadami G, Tran CD, Conlon M. Understanding dysbiosis and resilience in the human gut microbiome: biomarkers, interventions, and challenges. Front Microbiol 2025; 16:1559521. [PMID: 40104586 PMCID: PMC11913848 DOI: 10.3389/fmicb.2025.1559521] [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: 01/13/2025] [Accepted: 02/19/2025] [Indexed: 03/20/2025] Open
Abstract
The healthy gut microbiome is important in maintaining health and preventing various chronic and metabolic diseases through interactions with the host via different gut-organ axes, such as the gut-brain, gut-liver, gut-immune, and gut-lung axes. The human gut microbiome is relatively stable, yet can be influenced by numerous factors, such as diet, infections, chronic diseases, and medications which may disrupt its composition and function. Therefore, microbial resilience is suggested as one of the key characteristics of a healthy gut microbiome in humans. However, our understanding of its definition and indicators remains unclear due to insufficient experimental data. Here, we review the impact of key drivers including intrinsic and extrinsic factors such as diet and antibiotics on the human gut microbiome. Additionally, we discuss the concept of a resilient gut microbiome and highlight potential biomarkers including diversity indices and some bacterial taxa as recovery-associated bacteria, resistance genes, antimicrobial peptides, and functional flexibility. These biomarkers can facilitate the identification and prediction of healthy and resilient microbiomes, particularly in precision medicine, through diagnostic tools or machine learning approaches especially after antimicrobial medications that may cause stable dysbiosis. Furthermore, we review current nutrition intervention strategies to maximize microbial resilience, the challenges in investigating microbiome resilience, and future directions in this field of research.
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Affiliation(s)
- Azadeh Safarchi
- Microbiome for One Systems Health FSP, CSIRO, Westmead, NSW, Australia
- Health and Biosecurity Research Unit, CSIRO, Adelaide, SA, Australia
| | - Ghanyah Al-Qadami
- Microbiome for One Systems Health FSP, CSIRO, Westmead, NSW, Australia
- Health and Biosecurity Research Unit, CSIRO, Adelaide, SA, Australia
| | - Cuong D Tran
- Health and Biosecurity Research Unit, CSIRO, Adelaide, SA, Australia
| | - Michael Conlon
- Health and Biosecurity Research Unit, CSIRO, Adelaide, SA, Australia
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18
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Ang TL, Koo SH, Ang D, Tan CK, Wang LM, Wong SH, Chow PKH. Postcholecystectomy Gut Microbiome Changes and the Clinical Impact: A Systematic Review With Narrative Synthesis. J Gastroenterol Hepatol 2025; 40:574-583. [PMID: 39675817 DOI: 10.1111/jgh.16846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/21/2024] [Accepted: 11/23/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Cholecystectomy (CCE) can affect the enterohepatic circulation of bile acids and result in gut microbiome changes. This systematic review aimed to clarify the effect of CCE on gut microbiome composition and its clinical impact. METHOD A systematic search was conducted in PubMed, Web of Science, and Scopus, combining keywords such as "cholecystectomy" or "post-cholecystectomy" with "gut microbiome," "stool microbiome," or "gut dysbiosis." Data were extracted and synthesized using narrative review. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS A total of 1373 articles were screened and 14 studies were selected. Significant but inconsistent microbiome changes were reported. Changes were observed in alpha and beta diversity. At phylum level, an increase in Bacteroides and Ascomycota, decrease in Firmicutes, Actinomycetes, and Basidiomycota, and both increase and decrease in Fusobacteria were reported. At genus level, an increase in Prevotella and a decrease in Faecalibacterium were reported. In post-CCE diarrhea, decreased beta diversity, a decreased F/B ratio, an increase in Prevotella, an increase in Phocaeicola vulgatus, and a decrease in Prevotella copri were noted. For post-CCE syndrome, a higher abundance of Proteobacteria and decreased Firmicutes/Bacteroides (F/B) ratio were reported. A decreased relative abundance of Bifidobacterium longum subsp. longum from controls to CCE without colonic neoplasia to CCE with colonic neoplasia, and an increased abundance of Candida glabrata from controls, to CCE without colonic neoplasia and CCE with colonic neoplasia, were reported. CONCLUSION Patients who underwent CCE had significant gut dysbiosis. However, current studies could not clarify the detailed gut microbial structural and functional changes associated with CCE.
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Affiliation(s)
- Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Seok Hwee Koo
- Research Laboratory, Clinical Trials and Research Unit, Changi General Hospital, Singapore
| | - Daphne Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
| | - Chin Kimg Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lai Mun Wang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Department of Pathology, Parkway Laboratory Services Ltd, Singapore
| | - Sunny Hei Wong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore
| | - Pierce K H Chow
- Duke-NUS Medical School, Singapore
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, National Cancer Center and Singapore General Hospital, Singapore
- Program in Translational and Clinical Research in Liver Cancer, National Cancer Centre Singapore, Singapore
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19
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Joos R, Boucher K, Lavelle A, Arumugam M, Blaser MJ, Claesson MJ, Clarke G, Cotter PD, De Sordi L, Dominguez-Bello MG, Dutilh BE, Ehrlich SD, Ghosh TS, Hill C, Junot C, Lahti L, Lawley TD, Licht TR, Maguin E, Makhalanyane TP, Marchesi JR, Matthijnssens J, Raes J, Ravel J, Salonen A, Scanlan PD, Shkoporov A, Stanton C, Thiele I, Tolstoy I, Walter J, Yang B, Yutin N, Zhernakova A, Zwart H, Doré J, Ross RP. Examining the healthy human microbiome concept. Nat Rev Microbiol 2025; 23:192-205. [PMID: 39443812 DOI: 10.1038/s41579-024-01107-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2024] [Indexed: 10/25/2024]
Abstract
Human microbiomes are essential to health throughout the lifespan and are increasingly recognized and studied for their roles in metabolic, immunological and neurological processes. Although the full complexity of these microbial communities is not fully understood, their clinical and industrial exploitation is well advanced and expanding, needing greater oversight guided by a consensus from the research community. One of the most controversial issues in microbiome research is the definition of a 'healthy' human microbiome. This concept is complicated by the microbial variability over different spatial and temporal scales along with the challenge of applying a unified definition to the spectrum of healthy microbiome configurations. In this Perspective, we examine the progress made and the key gaps that remain to be addressed to fully harness the benefits of the human microbiome. We propose a road map to expand our knowledge of the microbiome-health relationship, incorporating epidemiological approaches informed by the unique ecological characteristics of these communities.
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Affiliation(s)
- Raphaela Joos
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Katy Boucher
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Aonghus Lavelle
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Manimozhiyan Arumugam
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Martin J Blaser
- Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA
| | - Marcus J Claesson
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Paul D Cotter
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre and VistaMilk SFI Research Centre, Moorepark, Fermoy, Moorepark, Ireland
| | - Luisa De Sordi
- Centre de Recherche Saint Antoine, Sorbonne Université, INSERM, Paris, France
| | | | - Bas E Dutilh
- Institute of Biodiversity, Faculty of Biological Sciences, Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany
- Theoretical Biology and Bioinformatics, Department of Biology, Science for Life, Utrecht University, Utrecht, The Netherlands
| | - Stanislav D Ehrlich
- Université Paris-Saclay, INRAE, MetaGenoPolis (MGP), Jouy-en-Josas, France
- Department of Clinical and Movement Neurosciences, University College London, London, UK
| | - Tarini Shankar Ghosh
- Department of Computational Biology, Indraprastha Institute of Information Technology Delhi (IIIT-Delhi), New Delhi, India
| | - Colin Hill
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Christophe Junot
- Département Médicaments et Technologies pour La Santé (DMTS), Université Paris-Saclay, CEA, INRAE, MetaboHUB, Gif-sur-Yvette, France
| | - Leo Lahti
- Department of Computing, University of Turku, Turku, Finland
| | - Trevor D Lawley
- Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, UK
| | - Tine R Licht
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Emmanuelle Maguin
- Université Paris-Saclay, INRAE, AgroParisTech, MICALIS, Jouy-en-Josas, France
| | - Thulani P Makhalanyane
- Department of Microbiology, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
| | - Julian R Marchesi
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Jelle Matthijnssens
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium
| | - Jeroen Raes
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium
- Vlaams Instituut voor Biotechnologie (VIB) Center for Microbiology, Leuven, Belgium
| | - Jacques Ravel
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Anne Salonen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Pauline D Scanlan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Andrey Shkoporov
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre and VistaMilk SFI Research Centre, Moorepark, Fermoy, Moorepark, Ireland
| | - Ines Thiele
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Medicine, University of Ireland, Galway, Ireland
| | - Igor Tolstoy
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
| | - Jens Walter
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
- Department of Medicine, University College Cork, Cork, Ireland
| | - Bo Yang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Natalia Yutin
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
| | - Alexandra Zhernakova
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Hub Zwart
- Erasmus School of Philosophy, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | - Joël Doré
- Université Paris-Saclay, INRAE, MetaGenoPolis (MGP), Jouy-en-Josas, France
- Université Paris-Saclay, INRAE, AgroParisTech, MICALIS, Jouy-en-Josas, France
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- School of Microbiology, University College Cork, Cork, Ireland.
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20
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Abbas M, Tangney M. The oncobiome; what, so what, now what? MICROBIOME RESEARCH REPORTS 2025; 4:16. [PMID: 40207280 PMCID: PMC11977386 DOI: 10.20517/mrr.2024.89] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/14/2025] [Accepted: 02/21/2025] [Indexed: 04/11/2025]
Abstract
Microbial communities inhabiting various body sites play critical roles in the initiation, progression, and treatment of cancer. The gut microbiota, a highly diverse microbial ecosystem, interacts with immune cells to modulate inflammation and immune surveillance, influencing cancer risk and therapeutic outcomes. Local tissue microbiota may impact the transition from premalignant states to malignancy. Characterization of the intratumoral microbiota increasingly reveals distinct microbiomes that may influence tumor growth, immune responses, and treatment efficacy. Various bacteria species have been reported to modulate cancer therapies through mechanisms such as altering drug metabolism and shaping the tumor microenvironment (TME). For instance, gut or intratumoral bacterial enzymatic activity can convert prodrugs into active forms, enhancing therapeutic effects or, conversely, inactivating small-molecule chemotherapeutics. Specific bacterial species have also been linked to improved responses to immunotherapy, underscoring the microbiome's role in treatment outcomes. Furthermore, unique microbial signatures in cancer patients, compared with healthy individuals, demonstrate the diagnostic potential of microbiota. Beyond the gut, tumor-associated and local microbiomes also affect therapy by influencing inflammation, tumor progression, and drug resistance. This review explores the multifaceted relationships between microbiomes and cancer, focusing on their roles in modulating the TME, immune activation, and treatment efficacy. The diagnostic and therapeutic potential of bacterial members of microbiota represents a promising avenue for advancing precision oncology and improving patient outcomes. By leveraging microbial biomarkers and interventions, new strategies can be developed to optimize cancer diagnosis and treatment.
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Affiliation(s)
- Munawar Abbas
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
- Cancer Research@UCC, University College Cork, Cork, T12 XF62, Ireland
| | - Mark Tangney
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
- Cancer Research@UCC, University College Cork, Cork, T12 XF62, Ireland
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21
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Hawley JA, Forster SC, Giles EM. Exercise, the Gut Microbiome and Gastrointestinal Diseases: Therapeutic Impact and Molecular Mechanisms. Gastroenterology 2025:S0016-5085(25)00329-4. [PMID: 39978410 DOI: 10.1053/j.gastro.2025.01.224] [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: 09/12/2024] [Revised: 01/16/2025] [Accepted: 01/25/2025] [Indexed: 02/22/2025]
Abstract
The benefits of regular physical activity (PA) on disease prevention and treatment outcomes have been recognized for centuries. However, only recently has interorgan communication triggered by the release of "myokines" from contracting skeletal muscles emerged as a putative mechanism by which exercise confers protection against numerous disease states. Cross-talk between active skeletal muscles and the gut microbiota reveal how regular PA boosts host immunity, facilitates a more diverse gut microbiome and functional metabolome, and plays a positive role in energy homeostasis and metabolic regulation. In contrast, and despite the large interindividual variation in the human gut microbiome, reduced microbial diversity has been implicated in several diseases of the gastrointestinal (GI) tract, systemic immune diseases, and cancers. Although prolonged, intense, weight-bearing exercise conducted in extreme conditions can increase intestinal permeability, compromising gut-barrier function and resulting in both upper and lower GI symptoms, these are transient and benign. Accordingly, the gut microbiome has become an attractive target for modulating many of the positive effects of regular PA on GI health and disease, although the precise dose of exercise required to induce favourable changes in the microbiome and enhance host immunity is currently unknown. Future efforts should concentrate on gaining a deeper understanding of the factors involved in exercise-gut interactions through the generation of functional 'omics readouts (ie, metatranscriptomics, metaproteomics, and metabolomics) that have the potential to identify functional traits of the microbiome that are linked to host health and disease states, and validating these interactions in experimental and preclinical systems. A greater understanding of how PA interacts with the GI tract and the microbiome may enable targeted therapeutic strategies to be developed for individuals and populations at risk for a variety of GI diseases.
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Affiliation(s)
- John A Hawley
- The Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia; Department of Sport and Exercise Sciences, Manchester Metropolitan University Institute of Sport, Manchester, United Kingdom.
| | - Samuel C Forster
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia
| | - Edward M Giles
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Victoria, Australia
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22
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O' Donovan CM, Nori SRC, Shanahan F, Celentano G, Murphy TB, Cotter PD, Sullivan OO. Temporal stability and lack of variance in microbiome composition and functionality in fit recreational athletes. Sci Rep 2025; 15:5619. [PMID: 39955324 PMCID: PMC11829997 DOI: 10.1038/s41598-025-88723-9] [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: 10/10/2024] [Accepted: 01/30/2025] [Indexed: 02/17/2025] Open
Abstract
Human gut microbiome composition and function is influenced by environmental and lifestyle factors, including exercise and fitness. We studied the composition and functionality of the faecal microbiome of recreational (non-elite) runners (n = 62) with serial shotgun metagenomics, at 4 time points over a 7-week period. Gut microbiome composition and function was stable over time. Grouping of samples on the basis of their fitness level (fair, good, excellent, and superior) or habitual training (low (4-6 h/week), medium (7-9 h/week), high (10-12 h/week), and extreme (13 + hours/week)) revealed no significant microbiome-related differences. Overall, the species Faecalibacterium prausnitzii, Blautia wexlerae, and Prevotella copri were the most abundant members of the gut microbiome. Analysis of co-abundance groups (CAGs) revealed no significant relationship between CAGs and fitness levels or training subgroups. Functional pathways were similar across all samples and timepoints with no clustering based on associated metadata. The most abundant genes identified within samples corresponded to pathways for nucleoside and nucleotide biosynthesis, amino acid biosynthesis, and cell wall biosynthesis. Collectively, these results describe the microbiome of active recreational runners and note temporal stability amongst participants.
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Affiliation(s)
- Ciara M O' Donovan
- APC Microbiome Ireland, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Sai Ravi Chandra Nori
- APC Microbiome Ireland, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Cork, Ireland
| | - Fergus Shanahan
- APC Microbiome Ireland, Cork, Ireland
- Department of Medicine, University College Cork, Cork, Ireland
| | - Gerardina Celentano
- School of Mathematics and Statistics, University College Dublin, Dublin, Ireland
| | - Thomas Brendan Murphy
- School of Mathematics and Statistics, University College Dublin, Dublin, Ireland
- VistaMilk, Fermoy, Cork, Ireland
| | - Paul D Cotter
- APC Microbiome Ireland, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Cork, Ireland
- VistaMilk, Fermoy, Cork, Ireland
| | - Orla O' Sullivan
- APC Microbiome Ireland, Cork, Ireland.
- Teagasc Food Research Centre, Moorepark, Cork, Ireland.
- VistaMilk, Fermoy, Cork, Ireland.
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23
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Tito Tadeo RY, Stensvold CR. Pitfalls in gut single-cell eukaryote research. Trends Parasitol 2025; 41:91-101. [PMID: 39814642 DOI: 10.1016/j.pt.2024.12.011] [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: 11/27/2024] [Revised: 12/18/2024] [Accepted: 12/18/2024] [Indexed: 01/18/2025]
Abstract
Gut single-celled eukaryotes (GSCEs) are found in billions of people worldwide, but we still know little about their functions and relationships in human gut ecology. Lately, retrospective analysis of bacterial data obtained by next-generation sequencing (NGS) methods has been used to identify links between GSCEs, gut bacteria, host metabolism, and host phenotypical traits, suggesting possible direct or indirect associations to favorable gut microbiome features and other health parameters. Here, we highlight some of the pitfalls related to the research strategy typically used so far and propose action points that could pave the way for a more accurate understanding of GSCEs in human health and disease.
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Affiliation(s)
- Raul Yhossef Tito Tadeo
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium
| | - Christen Rune Stensvold
- Laboratory of Parasitology, Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark; Department of Protozoology, Mahidol University, Bangkok, Thailand.
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24
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Kuziak A, Heczko P, Pietrzyk A, Strus M. Iron Homeostasis Dysregulation, Oro-Gastrointestinal Microbial Inflammatory Factors, and Alzheimer's Disease: A Narrative Review. Microorganisms 2025; 13:122. [PMID: 39858890 PMCID: PMC11767265 DOI: 10.3390/microorganisms13010122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 12/23/2024] [Accepted: 01/04/2025] [Indexed: 01/27/2025] Open
Abstract
Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder that profoundly impacts cognitive function and the nervous system. Emerging evidence highlights the pivotal roles of iron homeostasis dysregulation and microbial inflammatory factors in the oral and gut microbiome as potential contributors to the pathogenesis of AD. Iron homeostasis disruption can result in excessive intracellular iron accumulation, promoting the generation of reactive oxygen species (ROS) and oxidative damage. Additionally, inflammatory agents produced by pathogenic bacteria may enter the body via two primary pathways: directly through the gut or indirectly via the oral cavity, entering the bloodstream and reaching the brain. This infiltration disrupts cellular homeostasis, induces neuroinflammation, and exacerbates AD-related pathology. Addressing these mechanisms through personalized treatment strategies that target the underlying causes of AD could play a critical role in preventing its onset and progression.
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Affiliation(s)
- Agata Kuziak
- Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, św. Łazarza 16 Street, 31-008 Cracow, Poland;
- Department of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, Czysta 18 Street, 31-121 Cracow, Poland; (P.H.); (A.P.)
| | - Piotr Heczko
- Department of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, Czysta 18 Street, 31-121 Cracow, Poland; (P.H.); (A.P.)
| | - Agata Pietrzyk
- Department of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, Czysta 18 Street, 31-121 Cracow, Poland; (P.H.); (A.P.)
| | - Magdalena Strus
- Department of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, Czysta 18 Street, 31-121 Cracow, Poland; (P.H.); (A.P.)
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25
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Song S, Ning L, Yu J. Elucidating the causal relationship between gut microbiota, metabolites, and diabetic nephropathy in European patients: Revelations from genome-wide bidirectional mendelian randomization analysis. Front Endocrinol (Lausanne) 2025; 15:1391891. [PMID: 39845884 PMCID: PMC11750691 DOI: 10.3389/fendo.2024.1391891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 12/17/2024] [Indexed: 01/24/2025] Open
Abstract
Objective Previous observational studies suggest a potential link between gut microbiota, metabolites, and diabetic nephropathy. However, the exact causal relationship among these factors remains unclear. Method We conducted a two-sample bidirectional Mendelian randomization study using summary statistics from the IEU OpenGWAS Project database to investigate gut microbiota, metabolites, and diabetic nephropathy. A range of methods, including inverse variance weighting, MR-Egger, weighted median, and simple median, were applied to examine causal associations. Sensitivity analyses were performed to assess the robustness of the results. Additionally, reverse Mendelian randomization analysis was conducted, treating significant gut microbiota as the outcome, to evaluate effects and perform sensitivity testing. This comprehensive approach provided an in-depth assessment of the interactions among gut microbiota, metabolites, and diabetic nephropathy. Result The Inverse Variance Weighted estimates revealed that the abundance of Lachnospiraceae, Parasutterella, and Eubacterium exhibited negative causal effects on diabetic nephropathy, while Coprococcus, Sutterella, Faecalibacterium prausnitzii, and Bacteroides vulgatus showed protective causal effects against the condition. However, reverse Mendelian randomization analysis did not identify any significant associations between diabetic nephropathy and the identified gut microbiota. Furthermore, the estimates indicated that Cholesterol, Pyridoxate, Hexanoylcarnitine, X-12007, Octanoylcarnitine, 10-nonadecenoate (19:1n9), X-12734, and the average number of double bonds in a fatty acid chain had negative causal effects on diabetic nephropathy. In contrast, Methionine, Glycodeoxycholate, X-06351, 1-stearoylglycerol (1-monostearin), 5-dodecenoate (12:1n7), X-13859, 2-hydroxyglutarate, Glycoproteins, Phospholipids in IDL, and the concentration of small HDL particles demonstrated protective causal effects. Notably, sensitivity analyses did not detect any heterogeneity or horizontal pleiotropy, ensuring the robustness of the findings. Conclusion Modulating gut microbiota diversity and composition offers a promising strategy for improving the incidence and prognosis of diabetic nephropathy. This highlights the need for future clinical trials focusing on microbiome-based interventions, potentially utilizing microbiome-dependent metabolites. Such approaches could transform the treatment and management of diabetic nephropathy and its associated risk factors, paving the way for more effective therapeutic strategies to combat this debilitating condition.
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Affiliation(s)
- Siyuan Song
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Li Ning
- Department of Gynecology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangyi Yu
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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26
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Slykerman RF, Davies N, Vlckova K, O'Riordan KJ, Bassett SA, Dekker J, Schellekens H, Hyland NP, Clarke G, Patterson E. Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy. Microb Biotechnol 2025; 18:e70079. [PMID: 39815671 PMCID: PMC11735468 DOI: 10.1111/1751-7915.70079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 01/18/2025] Open
Abstract
Advancing microbiome-gut-brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo. For the therapeutic application of live microbial psychobiotics, consensus on their application as adjunct treatments to conventional neuromodulators, use in unmedicated populations or in at-risk cohorts with sub-clinical symptomatology is warranted. This missing information on both sides of the therapeutic equation when treating central nervous system (CNS) conditions makes psychobiotic research challenging, especially when compared to other pharmaceutical or functional food approaches. Expediting the transition from positive preclinical data to proven benefits in humans includes interpreting the promises and pitfalls of animal behavioural assays, as well as navigating mechanism-informed decision making to select the right microbe(s) for the job. In this review, we consider how these decisions can be supported in light of information accrued from a range of clinical studies across healthy, at-risk and pathological study populations, where specific strains have been evaluated in the context of gastrointestinal physiology, brain function and behaviour. Examples of successful, partial and unsuccessful translation from bench to bedside are considered. We also discuss the developments in in silico analyses that have enhanced our understanding of the gut microbiome and that have moved research towards pinpointing the host-microbe interactions most important for optimal gut-brain axis function. Combining this information with knowledge from functional assays across in vitro and ex vivo domains and incorporating model organisms can prime the discovery pipelines with the most promising and rationally selected psychobiotic candidates.
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Affiliation(s)
| | - Naomi Davies
- Department of Psychological MedicineUniversity of AucklandAucklandNew Zealand
| | - Klara Vlckova
- Fonterra Microbiome Research CentreUniversity College CorkCorkIreland
| | | | - Shalome A. Bassett
- Fonterra Research and Development CentrePalmerston NorthNew Zealand
- Riddet InstituteMassey UniversityPalmerston NorthNew Zealand
| | - James Dekker
- Fonterra Research and Development CentrePalmerston NorthNew Zealand
| | - Harriët Schellekens
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of Anatomy and NeuroscienceUniversity College CorkCorkIreland
| | - Niall P. Hyland
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of PhysiologyUniversity College CorkCorkIreland
| | - Gerard Clarke
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of Psychiatry and Neurobehavioural ScienceUniversity College CorkCorkIreland
| | - Elaine Patterson
- Fonterra Microbiome Research CentreUniversity College CorkCorkIreland
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27
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Shete O, Ghosh TS. Normal Gut Microbiomes in Diverse Populations: Clinical Implications. Annu Rev Med 2025; 76:95-114. [PMID: 39556491 DOI: 10.1146/annurev-med-051223-031809] [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] [Indexed: 11/20/2024]
Abstract
The human microbiome is a sensor and modulator of physiology and homeostasis. Remarkable tractability underpins the promise of therapeutic manipulation of the microbiome. However, the definition of a normal or healthy microbiome has been elusive. This is in part due to the underrepresentation of minority groups and major global regions in microbiome studies to date. We review studies of the microbiome in different populations and highlight a commonality among health-associated microbiome signatures along with major drivers of variation. We also provide an overview of microbiome-associated therapeutic interventions for some widespread, widely studied diseases. We discuss sources of bias and the challenges associated with defining population-specific microbiome reference bases. We propose a roadmap for defining normal microbiome references that can be used for population-customized microbiome therapeutics and diagnostics.
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Affiliation(s)
- Omprakash Shete
- Department of Computational Biology, Indraprastha Institute of Information Technology Delhi, New Delhi, Delhi, India;
| | - Tarini Shankar Ghosh
- Department of Computational Biology, Indraprastha Institute of Information Technology Delhi, New Delhi, Delhi, India;
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28
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Simbirtseva KY, O'Toole PW. Healthy and Unhealthy Aging and the Human Microbiome. Annu Rev Med 2025; 76:115-127. [PMID: 39531852 DOI: 10.1146/annurev-med-042423-042542] [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] [Indexed: 11/16/2024]
Abstract
An altered gut microbiome is a feature of many multifactorial diseases, and microbiome effects on host metabolism, immune function, and possibly neurological function are implicated. Increased biological age is accompanied by a change in the gut microbiome. However, age-related health loss does not occur uniformly across all subjects but rather depends on differential loss of gut commensals and gain of pathobionts. In this article, we summarize the known and possible effects of the gut microbiome on the hallmarks of aging and describe the most plausible mechanisms. Understanding and targeting these factors could lead to prolonging health span by rationally maintaining the gut microbiome.
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Affiliation(s)
- Kseniya Y Simbirtseva
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland;
| | - Paul W O'Toole
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland;
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García Mansilla MJ, Rodríguez Sojo MJ, Lista AR, Ayala Mosqueda CV, Ruiz Malagón AJ, Gálvez J, Rodríguez Nogales A, Rodríguez Sánchez MJ. Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential Therapeutic Effects of Probiotics and Their Metabolites. Nutrients 2024; 17:155. [PMID: 39796588 PMCID: PMC11723002 DOI: 10.3390/nu17010155] [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: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
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Affiliation(s)
- María José García Mansilla
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
| | - María Jesús Rodríguez Sojo
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - Andrea Roxana Lista
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | | | - Antonio Jesús Ruiz Malagón
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Málaga, Spain
| | - Julio Gálvez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
- CIBER de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alba Rodríguez Nogales
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - María José Rodríguez Sánchez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
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Ciernikova S, Sevcikova A, Novisedlakova M, Mego M. Insights into the Relationship Between the Gut Microbiome and Immune Checkpoint Inhibitors in Solid Tumors. Cancers (Basel) 2024; 16:4271. [PMID: 39766170 PMCID: PMC11674129 DOI: 10.3390/cancers16244271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/16/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025] Open
Abstract
Immunotherapy with immune checkpoint inhibitors represents a revolutionary approach to the treatment of solid tumors, including malignant melanoma, lung cancer, and gastrointestinal malignancies. Anti-CTLA-4 and anti-PD-1/PDL-1 therapies provide prolonged survival for cancer patients, but their efficacy and safety are highly variable. This review focuses on the crucial role of the gut microbiome in modulating the efficacy and toxicity of immune checkpoint blockade. Studies suggest that the composition of the gut microbiome may influence the response to immunotherapy, with specific bacterial strains able to promote an anti-tumor immune response. On the other hand, dysbiosis may increase the risk of adverse effects, such as immune-mediated colitis. Interventions aimed at modulating the microbiome, including the use of probiotics, prebiotics, fecal microbial transplantation, or dietary modifications, represent promising strategies to increase treatment efficacy and reduce toxicity. The combination of immunotherapy with the microbiome-based strategy opens up new possibilities for personalized treatment. In addition, factors such as physical activity and nutritional supplementation may indirectly influence the gut ecosystem and consequently improve treatment outcomes in refractory patients, leading to enhanced patient responses and prolonged survival.
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Affiliation(s)
- Sona Ciernikova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia;
| | - Aneta Sevcikova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia;
| | - Maria Novisedlakova
- Department of Oncology, Hospital Bory, Ivana Bukovčana 6118, 841 08 Bratislava, Slovakia;
| | - Michal Mego
- 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava and National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovakia;
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Yarahmadi A, Afkhami H, Javadi A, Kashfi M. Understanding the complex function of gut microbiota: its impact on the pathogenesis of obesity and beyond: a comprehensive review. Diabetol Metab Syndr 2024; 16:308. [PMID: 39710683 PMCID: PMC11664868 DOI: 10.1186/s13098-024-01561-z] [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: 10/10/2024] [Accepted: 12/15/2024] [Indexed: 12/24/2024] Open
Abstract
Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.
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Affiliation(s)
- Aref Yarahmadi
- Department of Biology, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
| | - Ali Javadi
- Department of Medical Sciences, Faculty of Medicine, Qom Medical Sciences, Islamic Azad University, Qom, Iran.
| | - Mojtaba Kashfi
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Fellowship in Clinical Laboratory Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
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Huang J, Lu Y, Tian F, Ni Y. Association of body index with fecal microbiome in children cohorts with ethnic-geographic factor interaction: accurately using a Bayesian zero-inflated negative binomial regression model. mSystems 2024; 9:e0134524. [PMID: 39570024 DOI: 10.1128/msystems.01345-24] [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: 10/09/2024] [Accepted: 10/24/2024] [Indexed: 11/22/2024] Open
Abstract
The exponential growth of high-throughput sequencing (HTS) data on the microbial communities presents researchers with an unparalleled opportunity to delve deeper into the association of microorganisms with host phenotype. However, this growth also poses a challenge, as microbial data are complex, sparse, discrete, and prone to zero inflation. Herein, by utilizing 10 distinct counting models for analyzing simulated data, we proposed an innovative Bayesian zero-inflated negative binomial (ZINB) regression model that is capable of identifying differentially abundant taxa associated with distinctive host phenotypes and quantifying the effects of covariates on these taxa. Our proposed model exhibits excellent accuracy compared with conventional Hurdle and INLA models, especially in scenarios characterized by inflation and overdispersion. Moreover, we confirm that dispersion parameters significantly affect the accuracy of model results, with defects gradually alleviating as the number of analyzed samples increases. Subsequently applying our model to amplicon data in real multi-ethnic children cohort, we found that only a subset of taxa were identified as having zero inflation in real data, suggesting that the prevailing understanding and processing of microbial count data in most previous microbiome studies were overly dogmatic. In practice, our pipeline of integrating bacterial differential abundance in microbiome data and relevant covariates is effective and feasible. Taken together, our method is expected to be extended to the microbiota studies of various multi-cohort populations. IMPORTANCE The microbiome is closely associated with physical indicators of the body, such as height, weight, age and BMI, which can be used as measures of human health. Accurately identifying which taxa in the microbiome are closely related to indicators of physical development is valuable as microbial markers of regional child growth trajectory. Zero-inflated negative binomial (ZINB) model, a type of Bayesian generalized linear model, can be effectively modeled in complex biological systems. We present an innovative ZINB regression model that is capable of identifying differentially abundant taxa associated with distinctive host phenotypes and quantifying the effects of covariates on these taxa, and demonstrate that its accuracy is superior to traditional Hurdle and INLA models. Our pipeline of integrating bacterial differential abundance in microbiome data and relevant covariates is effective and feasible.
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Affiliation(s)
- Jian Huang
- School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, China
- Key Laboratory of Xinjiang Special Probiotics and Dairy Technology, Shihezi University, Shihezi, Xinjiang, China
| | - Yanzhuan Lu
- School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, China
- Key Laboratory of Xinjiang Special Probiotics and Dairy Technology, Shihezi University, Shihezi, Xinjiang, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Yongqing Ni
- School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, China
- Key Laboratory of Xinjiang Special Probiotics and Dairy Technology, Shihezi University, Shihezi, Xinjiang, China
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Peng Y, Zhu J, Wang S, Liu Y, Liu X, DeLeon O, Zhu W, Xu Z, Zhang X, Zhao S, Liang S, Li H, Ho B, Ching JYL, Cheung CP, Leung TF, Tam WH, Leung TY, Chang EB, Chan FKL, Zhang L, Ng SC, Tun HM. A metagenome-assembled genome inventory for children reveals early-life gut bacteriome and virome dynamics. Cell Host Microbe 2024; 32:2212-2230.e8. [PMID: 39591974 DOI: 10.1016/j.chom.2024.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 10/03/2024] [Accepted: 10/24/2024] [Indexed: 11/28/2024]
Abstract
Existing microbiota databases are biased toward adult samples, hampering accurate profiling of the infant gut microbiome. Here, we generated a metagenome-assembled genome inventory for children (MAGIC) from a large collection of bulk and viral-like particle-enriched metagenomes from 0 to 7 years of age, encompassing 3,299 prokaryotic and 139,624 viral species-level genomes, 8.5% and 63.9% of which are unique to MAGIC. MAGIC improves early-life microbiome profiling, with the greatest improvement in read mapping observed in Africans. We then identified 54 candidate keystone species, including several Bifidobacterium spp. and four phages, forming guilds that fluctuated in abundance with time. Their abundances were reduced in preterm infants and were associated with childhood allergies. By analyzing the B. longum pangenome, we found evidence of phage-mediated evolution and quorum sensing-related ecological adaptation. Together, the MAGIC database recovers genomes that enable characterization of the dynamics of early-life microbiomes, identification of candidate keystone species, and strain-level study of target species.
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Affiliation(s)
- Ye Peng
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Jie Zhu
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Shilan Wang
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Yingzhi Liu
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Xin Liu
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Orlando DeLeon
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, The University of Chicago, Chicago, IL 60637, USA
| | - Wenyi Zhu
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Zhilu Xu
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Xi Zhang
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Shilin Zhao
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Suisha Liang
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China
| | - Hang Li
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China
| | - Brian Ho
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China
| | - Jessica Yuet-Ling Ching
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Chun Pan Cheung
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Ting Fan Leung
- Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR 999077, China; Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Wing Hung Tam
- Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Tak Yeung Leung
- Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Eugene B Chang
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, The University of Chicago, Chicago, IL 60637, USA
| | - Francis Ka Leung Chan
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR 999077, China; Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Lin Zhang
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China.
| | - Siew Chien Ng
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China; Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong SAR 999077, China.
| | - Hein Min Tun
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China; Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China.
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Deehan EC, Al Antwan S, Witwer RS, Guerra P, John T, Monheit L. Revisiting the Concepts of Prebiotic and Prebiotic Effect in Light of Scientific and Regulatory Progress-A Consensus Paper From the Global Prebiotic Association. Adv Nutr 2024; 15:100329. [PMID: 39481540 PMCID: PMC11616045 DOI: 10.1016/j.advnut.2024.100329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 10/18/2024] [Accepted: 10/25/2024] [Indexed: 11/02/2024] Open
Abstract
The term prebiotic has been used for almost 3 decades and has undergone numerous updates over the years. The scientific literature reveals that despite continuous efforts to establish a globally unified definition to guide jurisdictional regulations and product innovations, ambiguity continues to surround the terms prebiotic and prebiotic effect, leading to products that lack in full regulatory adherence being marketed worldwide. Thus, to reflect the current state of scientific research and knowledge and for the continuous advancement of the category, an update to the current prebiotic definition is warranted. This update includes removing the term selectivity, considering additional locations of action besides the gut, highlighting prebiotic performance benefits such as cognitive and athletic, and providing a clear standalone definition for prebiotic effect. The Global Prebiotic Association (GPA) is a leading information and industry hub committed to raising awareness about prebiotics, their emerging and well-established health benefits, and prebiotic product integrity and efficacy. In this position paper, GPA builds on previous prebiotic definitions to propose the following expanded definition for prebiotic: "a compound or ingredient that is utilized by the microbiota producing a health or performance benefit." In addition to prebiotic, GPA also defines prebiotic effect as "a health or performance benefit that arises from alteration of the composition and/or activity of the microbiota, as a direct or indirect result of the utilization of a specific and well-defined compound or ingredient by microorganisms." With these 2 definitions, GPA aims to paint a clearer picture for the term prebiotic, and by incorporating an industry point of view, these updated definitions may be used alongside current scientific and regulatory perspectives to move the category forward.
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Affiliation(s)
- Edward C Deehan
- Department of Food Science and Technology, University of Nebraska, Lincoln, NE, United States; Nebraska Food for Health Center, University of Nebraska, Lincoln, NE, United States; Scientific & Technical Committee, Global Prebiotic Association, Chicago, IL, United States.
| | | | - Rhonda S Witwer
- Scientific & Technical Committee, Global Prebiotic Association, Chicago, IL, United States; ADM, Decatur, IL, United States
| | - Paula Guerra
- Scientific & Technical Committee, Global Prebiotic Association, Chicago, IL, United States; SGS Nutrasource, Guelph, Ontario, Canada.
| | - Tania John
- Scientific & Technical Committee, Global Prebiotic Association, Chicago, IL, United States; SGS Nutrasource, Guelph, Ontario, Canada
| | - Len Monheit
- Scientific & Technical Committee, Global Prebiotic Association, Chicago, IL, United States; Global Prebiotic Association/Industry Transparency Center, Chicago, IL, United States
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Scicchitano D, Foresto L, Laczny CC, Cinti N, Vitagliano R, Halder R, Morri G, Turroni S, D'Amico F, Palladino G, Fiori J, Wilmes P, Rampelli S, Candela M. A 15-day pilot biodiversity intervention with horses in a farm system leads to gut microbiome rewilding in 10 urban Italian children. One Health 2024; 19:100902. [PMID: 39399231 PMCID: PMC11470462 DOI: 10.1016/j.onehlt.2024.100902] [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: 04/24/2024] [Revised: 09/20/2024] [Accepted: 09/22/2024] [Indexed: 10/15/2024] Open
Abstract
To provide some glimpses on the possibility of shaping the human gut microbiome (GM) through probiotic exchange with natural ecosystems, here we explored the impact of 15 days of daily interaction with horses on the GM of 10 urban-living Italian children. Specifically, the children were in close contact with the horses in an "educational farm", where they spent almost 10 h/day interacting with the animals. The children's GM was assessed before and after the horse interaction using metabarcoding sequencing and shotgun metagenomics, along with the horses' skin, oral and fecal microbiomes. Targeted metabolomic analysis for GM-produced beneficial metabolites (i.e., short-chain fatty acids) in the children's feces was also performed. Interaction with horses facilitated the acquisition of health-related traits in the children's GM, such as increased diversity, enhanced butyrate production and an increase in several health-promoting species considered to be next-generation probiotics. Among these, the butyrate producers Facecalibacterium prausnitzii and F. duncaniae and a species belonging to the order Christensenellales. Interaction with horses was also associated with increased proportions of Eggerthella lenta, Gordonibacter pamelae and G. urolithinfaciens, GM components known to play a role in the bioconversion of dietary plant polyphenols into beneficial metabolites. Notably, no increase in potentially harmful traits, including toxin genes, was observed. Overall, our pilot study provides some insights on the existence of possible health-promoting exchanges between children and horses microbiomes. It lays the groundwork for an implemented and more systematic enrollment effort to explore the full complexity of human GM rewilding through exchange with natural ecosystems, aligning with the One Health approach.
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Affiliation(s)
- Daniel Scicchitano
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
- Fano Marine Center, The Inter-Institute Center for Research on Marine Biodiversity, Resources and Biotechnologies, 61032 Fano, Italy
| | - Lucia Foresto
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
- Fano Marine Center, The Inter-Institute Center for Research on Marine Biodiversity, Resources and Biotechnologies, 61032 Fano, Italy
| | - Cédric C. Laczny
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Nicoló Cinti
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
- Fano Marine Center, The Inter-Institute Center for Research on Marine Biodiversity, Resources and Biotechnologies, 61032 Fano, Italy
| | - Rosalba Vitagliano
- Department of Chemistry “Giacomo Ciamician”, Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
| | - Rashi Halder
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Gaja Morri
- Psy D., Psychotherapist, Psychoanalyst, via M. Serenari, 7, 40033 Casalecchio di Reno, Bologna, Italy
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
| | - Federica D'Amico
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
| | - Giorgia Palladino
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
- Fano Marine Center, The Inter-Institute Center for Research on Marine Biodiversity, Resources and Biotechnologies, 61032 Fano, Italy
| | - Jessica Fiori
- Department of Chemistry “Giacomo Ciamician”, Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
- Institute of Neurological Sciences of Bologna (IRCCS), Laboratory of Proteomics Metabolomics and Bioanalitical Chemistry, 40124 Bologna, Italy
| | - Paul Wilmes
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Simone Rampelli
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
- Fano Marine Center, The Inter-Institute Center for Research on Marine Biodiversity, Resources and Biotechnologies, 61032 Fano, Italy
| | - Marco Candela
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, 40126 Bologna, Italy
- Fano Marine Center, The Inter-Institute Center for Research on Marine Biodiversity, Resources and Biotechnologies, 61032 Fano, Italy
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Lee JY, Kim Y, Kim J, Kim JK. Fecal Microbiota Transplantation: Indications, Methods, and Challenges. J Microbiol 2024; 62:1057-1074. [PMID: 39557804 DOI: 10.1007/s12275-024-00184-3] [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: 07/09/2024] [Revised: 09/25/2024] [Accepted: 10/16/2024] [Indexed: 11/20/2024]
Abstract
Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.
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Affiliation(s)
- Jee Young Lee
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Yehwon Kim
- Department of Medicine, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Jiyoun Kim
- Department of Medicine, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Jiyeun Kate Kim
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea.
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Saadh MJ, Ahmed HH, Al-Hussainy AF, Kaur I, Kumar A, Chahar M, Saini S, Taher WM, Alwan M, Jawad MJ, Darvishi M, Alsaikhan F. Bile's Hidden Weapon: Modulating the Microbiome and Tumor Microenvironment. Curr Microbiol 2024; 82:25. [PMID: 39614901 DOI: 10.1007/s00284-024-04004-0] [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: 08/31/2024] [Accepted: 11/20/2024] [Indexed: 12/07/2024]
Abstract
The human gut microbiome is a dynamic and intricate ecosystem, composed of trillions of microorganisms that play a pivotal role in maintaining overall health and well-being. However, the gut microbiome is constantly exposed to various environmental factors, including the bile produced by the liver, which can significantly impact its composition and function. Bile acids, secreted by the liver and stored in the gallbladder, modulate the gut microbiome, influencing its composition and function. This altered microbiome profile can, in turn, impact the tumor microenvironment (TME), promoting an immunosuppressive environment that favors tumor growth and metastasis. Furthermore, changes in the gut microbiome can also influence the production of bile acids and other metabolites that directly affect cancer cells and their behavior. Moreover, bile acids have been shown to shape the microbiome and increase antibiotic resistance, underscoring the need for targeted interventions. This review provides a comprehensive overview of the intricate relationships between bile, the gut microbiome, and the TME, highlighting the mechanisms by which this interplay drives cancer progression and resistance to therapy. Understanding these complex interactions is crucial for developing novel therapeutic strategies that target the gut-bile-TME axis and improve patient outcomes.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | | | | | - Irwanjot Kaur
- Department of Biotechnology and Genetics, Jain (Deemed-to-Be) University, Bengaluru, Karnataka, 560069, India
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India
| | - Abhishek Kumar
- School of Pharmacy-Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Gangoh, Uttar Pradesh, 247341, India
- Department of Pharmacy, Arka Jain University, Jamshedpur, Jharkhand, 831001, India
| | - Mamata Chahar
- Department of Chemistry, NIMS Institute of Engineering & Technology, NIMS University, Rajasthan, Jaipur, India
| | - Suman Saini
- Department of Applied Sciences, Chandigarh Engineering College, Chandigarh Group of Colleges-Jhanjeri, Mohali, Punjab, 140307, India
| | - Waam Mohammed Taher
- College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
| | - Mariem Alwan
- Pharmacy College, Al-Farahidi University, Baghdad, Iraq
| | | | - Mohammad Darvishi
- Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Department of Aerospace and Subaquatic Medicine, AJA University of Medical Sciences, Tehran, Iran.
| | - Fahad Alsaikhan
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia
- School of Pharmacy, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
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Bajaj A, Markandey M, Samal A, Goswami S, Vuyyuru SK, Mohta S, Kante B, Kumar P, Makharia G, Kedia S, Ghosh TS, Ahuja V. Depletion of core microbiome forms the shared background against diverging dysbiosis patterns in Crohn's disease and intestinal tuberculosis: insights from an integrated multi-cohort analysis. Gut Pathog 2024; 16:65. [PMID: 39511674 PMCID: PMC11545864 DOI: 10.1186/s13099-024-00654-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 10/06/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND/AIMS Crohn's disease (CD) and intestinal tuberculosis (ITB) are gastrointestinal (GI) inflammatory disorders with overlapping clinical presentations but diverging etiologies. The study aims to decipher CD and ITB-associated gut dysbiosis signatures and identify disease-associated co-occurring modules to evaluate whether this dysbiosis signature is a disease-specific trait or is a shared feature across diseases of diverging etiologies. METHODS Disease-associated gut microbial modules were identified using statistical machine learning and co-abundance network analysis in controls, CD and ITB patients recruited as part of this study. Module reproducibility was reinvestigated through meta-network analysis encompassing >5400 bacteriomes and ~900 mycobiomes. Subsequently, >1600 Indian gut microbiomes were analyzed to identify a central-core gut microbiome of 46 taxa, whose abundances aided in the formulation of an India-specific Core Gut Microbiome Score (CGMS) to measure the degree of core retention. RESULTS Both diseases witness similar patterns of alterations in [alpha]-diversity, characterized by a significant reduction in gut bacterial (i.e., bacterial/archaeal) diversity and a concomitant increase in the fungal [alpha]-diversity. Specific bacterial taxa, along with the diverging mycobiome enabled distinction between the diseases. Co-abundance network analysis of these taxa, validated by integrated meta-network analysis, revealed a 'disease-depleted' module, consistent across multiple cohorts, with >75% of this module constituting the central-core Indian gut microbiome. CGMS robustly assessed the core-microbiome loss across different stages of gut inflammatory disorders, in Indian and international cohorts. CONCLUSIONS While the disease-specific gain of detrimental bacteria forms an important component of gut dysbiosis, loss of the core microbiome is a shared phenomenon contributing to various GI disorders.
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Affiliation(s)
- Aditya Bajaj
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Manasvini Markandey
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Amit Samal
- Department of Computational Biology, Indraprastha Institute of Information Technology-Delhi, New Delhi, India
| | - Sourav Goswami
- Department of Computational Biology, Indraprastha Institute of Information Technology-Delhi, New Delhi, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Srikant Mohta
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Bhaskar Kante
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Peeyush Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Tarini Shankar Ghosh
- Department of Computational Biology, Indraprastha Institute of Information Technology-Delhi, New Delhi, India.
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Zumkhawala-Cook A, Gallagher P, Raymann K. Diet affects reproductive development and microbiota composition in honey bees. Anim Microbiome 2024; 6:64. [PMID: 39501371 PMCID: PMC11539837 DOI: 10.1186/s42523-024-00350-3] [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: 09/08/2024] [Accepted: 10/23/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND Gut microbes are important to the health and fitness of many animals. Many factors have been shown to affect gut microbial communities including diet, lifestyle, and age. Most animals have very complex physiologies, lifestyles, and microbiomes, making it virtually impossible to disentangle what factors have the largest impact on microbiota composition. Honeybees are an excellent model to study host-microbe interactions due to their relatively simple gut microbiota, experimental tractability, and eusociality. Worker honey bees have distinct gut microbiota from their queen mothers despite being close genetic relatives and living in the same environment. Queens and workers differ in numerous ways including development, physiology, pheromone production, diet, and behavior. In the prolonged absence of a queen or Queen Mandibular Pheromones (QMP), some but not all workers will develop ovaries and become "queen-like". Using this inducible developmental change, we aimed to determine if diet and/or reproductive development impacts the gut microbiota of honey bee workers. RESULTS Microbiota-depleted newly emerged workers were inoculated with a mixture of queen and worker gut homogenates and reared under four conditions varying in diet and pheromone exposure. Three weeks post-emergence, workers were evaluated for ovary development and their gut microbiota communities were characterized. The proportion of workers with developed ovaries was increased in the absence of QMP but also when fed a queen diet (royal jelly). Overall, we found that diet, rather than reproductive development or pheromone exposure, led to more "queen-like" microbiota in workers. However, we revealed that diet alone cannot explain the microbiota composition of workers. CONCLUSION The hypothesis that reproductive development explains microbiota differences between queens and workers was rejected. We found evidence that diet is one of the main drivers of differences between the gut microbial community compositions of queens and workers but cannot fully explain the distinct microbiota of queens. Thus, we predict that behavioral and other physiological differences dictate microbiota composition in workers and queens. Our findings not only contribute to our understanding of the factors affecting the honey bee microbiota, which is important for bee health, but also illustrate the versatility and benefits of utilizing honeybees as a model system to study host-microbe interactions.
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Affiliation(s)
- Anjali Zumkhawala-Cook
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina, USA
- Department of Biochemistry and Molecular Biology, Kenyon College, Gambier, Ohio, USA
| | - Patrick Gallagher
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina, USA
| | - Kasie Raymann
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina, USA.
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Ross FC, Patangia D, Grimaud G, Lavelle A, Dempsey EM, Ross RP, Stanton C. The interplay between diet and the gut microbiome: implications for health and disease. Nat Rev Microbiol 2024; 22:671-686. [PMID: 39009882 DOI: 10.1038/s41579-024-01068-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2024] [Indexed: 07/17/2024]
Abstract
Diet has a pivotal role in shaping the composition, function and diversity of the gut microbiome, with various diets having a profound impact on the stability, functionality and diversity of the microbial community within our gut. Understanding the profound impact of varied diets on the microbiome is crucial, as it will enable us not only to make well-informed dietary decisions for better metabolic and intestinal health, but also to prevent and slow the onset of specific diet-related diseases that stem from suboptimal diets. In this Review, we explore how geographical location affects the gut microbiome and how different diets shape its composition and function. We examine the mechanisms by which whole dietary regimes, such as the Mediterranean diet, high-fibre diet, plant-based diet, high-protein diet, ketogenic diet and Western diet, influence the gut microbiome. Furthermore, we underscore the need for exhaustive studies to better understand the causal relationship between diet, host and microorganisms for the development of precision nutrition and microbiome-based therapies.
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Affiliation(s)
- Fiona C Ross
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Dhrati Patangia
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Moorepark Food Research Centre, Cork, Ireland
| | - Ghjuvan Grimaud
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Moorepark Food Research Centre, Cork, Ireland
| | - Aonghus Lavelle
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Eugene M Dempsey
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
- INFANT Centre, University College Cork, Cork, Ireland
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
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Lamminpää I, Boem F, Amedei A. Health-promoting worms? Prospects and pitfalls of helminth therapy. Bioessays 2024; 46:e2400080. [PMID: 39263744 DOI: 10.1002/bies.202400080] [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: 04/04/2024] [Revised: 08/28/2024] [Accepted: 09/02/2024] [Indexed: 09/13/2024]
Abstract
In this manuscript, we explore the potential therapeutic use of helminths. After analyzing helminths' role in connection with human health from the perspective of their symbiotic and evolutionary relationship, we critically examine some studies on their therapeutic applications. In doing so, we focus on some prominent mechanisms of action and potential benefits, but also on the exaggerations and theoretical and methodological difficulties of such proposals. We conclude that further studies are needed to fully explore the potential benefits of this perspective, and we encourage the scientific community in doing so.
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Affiliation(s)
- Ingrid Lamminpää
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Federico Boem
- Institut für Philosophie I, Ruhr-Universität Bochum, Bochum, Germany
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Interdisciplinary Internal Medicine Unit, Careggi University Hospital, Florence, Italy
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Khalaf R, Sciberras M, Ellul P. The role of the fecal microbiota in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2024; 36:1249-1258. [PMID: 38973540 DOI: 10.1097/meg.0000000000002818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
The understanding of the potential role of the microbiota in the pathogenesis of inflammatory bowel disease (IBD) is ever-evolving. Traditionally, the management of IBD has involved medical therapy and/or surgical intervention. IBD can be characterized by gut microbiome alterations through various pathological processes. Various studies delve into nontraditional methods such as probiotics and fecal microbiota transplant and their potential therapeutic effects. Fecal microbiota transplant involves the delivery of a balanced composition of gut microorganisms into an affected patient via multiple possible routes and methods, while probiotics consist of live microorganisms given via the oral route. At present, neither method is considered first-line treatment, however, fecal microbiota transplant has shown potential success in inducing and maintaining remission in ulcerative colitis. In a study by Kruis and colleagues, Escherichia coli Nissle 1917 was considered to be equivalent to mesalamine in mild ulcerative colitis. Alteration of the microbiome in the management of Crohn's disease is less well defined. Furthermore, variation in the clinical usefulness of 5-aminosalicylic acid medication has been attributed, in part, to its acetylation and inactivation by gut microbes. In summary, our understanding of the microbiome's role is continually advancing, with the possibility of paving the way for personalized medicine based on the microbiome.
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Affiliation(s)
- Rami Khalaf
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | - Pierre Ellul
- Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
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Fan S, Zhang Z, Nie Q, Ackah M, Nie S. Rethinking the classification of non-digestible carbohydrates: Perspectives from the gut microbiome. Compr Rev Food Sci Food Saf 2024; 23:e70046. [PMID: 39437196 DOI: 10.1111/1541-4337.70046] [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: 04/27/2024] [Revised: 08/23/2024] [Accepted: 09/30/2024] [Indexed: 10/25/2024]
Abstract
Clarification is required when the term "carbohydrate" is used interchangeably with "saccharide" and "glycan." Carbohydrate classification based on human digestive enzyme activities brings clarity to the energy supply function of digestible sugars and starch. However, categorizing structurally diverse non-digestible carbohydrates (NDCs) to make dietary intake recommendations for health promotion remains elusive. In this review, we present a summary of the strengths and weaknesses of the traditional dichotomic classifications of carbohydrates, which were introduced by food chemists, nutritionists, and microbiologists. In parallel, we discuss the current consensus on commonly used terms for NDCs such as "dietary fiber," "prebiotics," and "fermentable glycans" and highlight their inherent differences from the perspectives of gut microbiome. Moreover, we provide a historical perspective on the development of novel concepts such as microbiota-accessible carbohydrates, microbiota-directed fiber, targeted prebiotics, and glycobiome. Crucially, these novel concepts proposed by multidisciplinary scholars help to distinguish the interactions between diverse NDCs and the gut microbiome. In summary, the term NDCs created based on the inability of human digestive enzymes fails to denote their interactions with gut microbiome. Considering that the gut microbiome possesses sophisticated enzyme systems to harvest diverse NDCs, the subclassification of NDCs should be realigned to their metabolism by various gut microbes, particularly health-promoting microbes. Such rigorous categorizations facilitate the development of microbiome-targeted therapeutic strategies by incorporating specific types of NDCs.
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Affiliation(s)
- Songtao Fan
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
- State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China
| | - Zhihong Zhang
- School of Grain Science and Technology, Jiangsu University of Science and Technology, Zhenjiang, China
- State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China
| | - Qixing Nie
- State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China
| | - Michael Ackah
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China
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Belnap N, Ramsey K, Carvalho ST, Nearman L, Haas H, Huentelman M, Lee K. Exploring the Frontier: The Human Microbiome's Role in Rare Childhood Neurological Diseases and Epilepsy. Brain Sci 2024; 14:1051. [PMID: 39595814 PMCID: PMC11592123 DOI: 10.3390/brainsci14111051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 10/19/2024] [Accepted: 10/19/2024] [Indexed: 11/28/2024] Open
Abstract
Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut-brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this disease and other rare neurological diseases.
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Affiliation(s)
- Newell Belnap
- Center for Rare Childhood Disorders, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA; (N.B.)
| | - Keri Ramsey
- Center for Rare Childhood Disorders, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA; (N.B.)
| | | | - Lexi Nearman
- Department of Biological Science, Northern Arizona University, Flagstaff, AZ 86011, USA
- TGen Integrated Microbiomics Center, Translational Genomics Research Institute (TGen), Flagstaff, AZ 86011, USA
| | - Hannah Haas
- Center for Rare Childhood Disorders, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA; (N.B.)
- Barrett, the Honors College, Arizona State University, Tempe, AZ 85281, USA
| | - Matt Huentelman
- Center for Rare Childhood Disorders, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA; (N.B.)
| | - Keehoon Lee
- TGen Integrated Microbiomics Center, Translational Genomics Research Institute (TGen), Flagstaff, AZ 86011, USA
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Connolly D, Minj J, Murphy KM, Solverson PM, Rust BM, Carbonero F. Impact of quinoa and food processing on gastrointestinal health: a narrative review. Crit Rev Food Sci Nutr 2024:1-14. [PMID: 39422522 DOI: 10.1080/10408398.2024.2416476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Due to exceptional nutritional quality, quinoa is an ideal candidate to solve food insecurity in many countries. Quinoa's profile of polyphenols, essential amino acids, and lipids make it ideal for digestive health. How the nutrient profile and bioavailability of quinoa metabolites differs across cooking methods such as heat, pressure, and time employed has yet to be elucidated. The objective of this review is to compile available research pertaining to the impact of various cooking methods on quinoa's nutritional properties with specific emphasis on how those properties affect gut health. Replacing small percentages of wheat flour with quinoa flour in baked bread increases the antioxidant activity, essential amino acids, fiber, minerals, and polyphenols. Extruding quinoa flour reduces amino acid, lipid, and polyphenol content of the raw seed, however direct quinoa and cereal grain extrudate comparisons are absent. Boiling quinoa leads to an increase of dietary fiber as well as exceptional retention of amino acids, lipids, and polyphenols. Baking and extruding with quinoa flour results in less optimal texture due to higher density, however minor substitutions can retain acceptable texture and even improve taste. Future research on quinoa's substitution in common processing methods will create equally desirable, yet more nutritious food products.
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Affiliation(s)
- Devin Connolly
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
| | - Jagrani Minj
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
| | - Kevin M Murphy
- Department of Crop and Soil Science, Washington State University, Pullman, Washington, USA
| | - Patrick M Solverson
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
| | - Bret M Rust
- Department of Applied Health Science, Indiana University School of Public Health-Bloomington, Bloomington, Indiana, USA
| | - Franck Carbonero
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
- School of Food Science, Washington State University, Spokane, Washington, USA
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46
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Tannock GW. The human gut metacommunity as a conceptual aid in the development of precision medicine. Front Microbiol 2024; 15:1469543. [PMID: 39464395 PMCID: PMC11503762 DOI: 10.3389/fmicb.2024.1469543] [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: 07/24/2024] [Accepted: 09/13/2024] [Indexed: 10/29/2024] Open
Abstract
Human gut microbiomes (microbiotas) are highly individualistic in taxonomic composition but nevertheless are functionally similar. Thus, collectively, they comprise a "metacommunity." In ecological terminology, the assembly of human gut microbiomes is influenced by four processes: selection, speciation, drift, and dispersal. As a result of fortuitous events associated with these processes, individual microbiomes are taxonomically "tailor-made" for each host. However, functionally they are "off-the-shelf" because of similar functional outputs resulting from metabolic redundancy developed in host-microbe symbiosis. Because of this, future microbiological and molecular studies of microbiomes should emphasize the metabolic interplay that drives the human gut metacommunity and that results in these similar functional outputs. This knowledge will support the development of remedies for specific functional dysbioses and hence provide practical examples of precision medicine.
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Affiliation(s)
- Gerald W. Tannock
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
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47
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McBurney MI, Cho CE. Understanding the role of the human gut microbiome in overweight and obesity. Ann N Y Acad Sci 2024; 1540:61-88. [PMID: 39283061 DOI: 10.1111/nyas.15215] [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] [Indexed: 10/14/2024]
Abstract
The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.
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Affiliation(s)
- Michael I McBurney
- Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
- Division of Biochemical and Molecular Biology, Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, USA
| | - Clara E Cho
- Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
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Krause JL, Engelmann B, Lallinger DJD, Rolle-Kampczyk U, von Bergen M, Chang HD. Multi-Omics Analysis Unravels the Impact of Stool Sample Logistics on Metabolites and Microbial Composition. Microorganisms 2024; 12:1998. [PMID: 39458307 PMCID: PMC11509235 DOI: 10.3390/microorganisms12101998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 10/28/2024] Open
Abstract
Human health and the human microbiome are inevitably intertwined, increasing their relevance in clinical research. However, the collection, transportation and storage of faecal samples may introduce bias due to methodological differences, especially since postal shipping is a common practise in large-scale clinical cohort studies. Using four different Omics layer, we determined the structural (16S rRNA sequencing, cytometric microbiota profiling) and functional integrity (SCFAs, global metabolome) of the microbiota in relation to different easy-to-handle conditions. These conditions were storage at -20 °C, -20 °C as glycerol stock, 4 °C and room temperature with and without oxygen exposure for a maximum of one week. Storage time affected the microbiota on all Omics levels. However, the magnitude was donor-dependent, highlighting the need for purpose-optimized sample collection in clinical multi-donor studies. The effects of oxygen exposure were negligible for all analyses. At ambient temperature, SCFA and compositional profiles were stable for 24 h and 48 h, respectively, while at 4 °C, SCFA profiles were maintained for 48 h. The global metabolome was highly susceptible, already changing at 24 h in non-frozen conditions. Thus, faecal microbiota was best preserved on all levels when transported as a native sample frozen within 24 h, leading to the least biased outcomes in the analysis. We conclude that the immediate freezing of native stool samples for transportation to the lab is best suited for planned multi-Omics analyses that include metabolomics to extend standard sequencing approaches.
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Affiliation(s)
- Jannike L. Krause
- German Rheumatism Research Center Berlin, A Leibniz Institute—DRFZ, Schwiete Laboratory for Microbiota and Inflammation, 10117 Berlin, Germany; (D.J.D.L.); (H.-D.C.)
| | - Beatrice Engelmann
- Helmholtz-Centre for Environmental Research—UFZ, Department of Molecular Toxicology, 04318 Leipzig, Germany; (B.E.); (U.R.-K.); (M.v.B.)
| | - David J. D. Lallinger
- German Rheumatism Research Center Berlin, A Leibniz Institute—DRFZ, Schwiete Laboratory for Microbiota and Inflammation, 10117 Berlin, Germany; (D.J.D.L.); (H.-D.C.)
| | - Ulrike Rolle-Kampczyk
- Helmholtz-Centre for Environmental Research—UFZ, Department of Molecular Toxicology, 04318 Leipzig, Germany; (B.E.); (U.R.-K.); (M.v.B.)
| | - Martin von Bergen
- Helmholtz-Centre for Environmental Research—UFZ, Department of Molecular Toxicology, 04318 Leipzig, Germany; (B.E.); (U.R.-K.); (M.v.B.)
- Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, 04103 Leipzig, Germany
- German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, 04103 Leipzig, Germany
| | - Hyun-Dong Chang
- German Rheumatism Research Center Berlin, A Leibniz Institute—DRFZ, Schwiete Laboratory for Microbiota and Inflammation, 10117 Berlin, Germany; (D.J.D.L.); (H.-D.C.)
- Department for Cytometry, Institute of Biotechnology, Technical University Berlin, 10115 Berlin, Germany
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49
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Misera A, Marlicz W, Podkówka A, Łoniewski I, Skonieczna-Żydecka K. Possible application of Akkermansia muciniphila in stress management. MICROBIOME RESEARCH REPORTS 2024; 3:48. [PMID: 39741949 PMCID: PMC11684984 DOI: 10.20517/mrr.2023.81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 01/03/2025]
Abstract
Akkermansia muciniphila (A. muciniphila) is a promising candidate bacterium for stress management due to its beneficial effects on the microbiota-gut-brain axis (MGBA). As a well-known mucin-degrading bacterium in the digestive tract, A. muciniphila has demonstrated significant benefits for host physiology. Recent research highlights its potential in treating several neuropsychiatric disorders. Proposed mechanisms of action include the bacterium's outer membrane protein Amuc_1100 and potentially its extracellular vesicles (EVs), which interact with host immune receptors and influence serotonin pathways, which are crucial for emotional regulation. Despite its potential, the administration of probiotics containing A. muciniphila faces technological challenges, prompting the development of pasteurized forms recognized as safe by the European Food Safety Authority (EFSA). This review systematically examines the existing literature on the role of A. muciniphila in stress management, emphasizing the need for further research to validate its efficacy. The review follows a structured methodology, including comprehensive database searches and thematic data analysis, to provide a detailed understanding of the relationship between stress, microbiota, and A. muciniphila therapeutic potential.
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Affiliation(s)
- Agata Misera
- Department of Psychiatry, Pomeranian Medical University in Szczecin, Szczecin 71-460, Poland
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Szczecin 71-252, Poland
| | - Albert Podkówka
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin 71-460, Poland
| | - Igor Łoniewski
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin 71-460, Poland
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50
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Elsawy NA, Ibrahiem AH, Younis GA, Meheissen MA, Abdel-Fattah YH. Microbiome and Femoral Cartilage Thickness in Knee Osteoarthritis: Is There a Link? Cartilage 2024:19476035241276852. [PMID: 39235213 PMCID: PMC11569570 DOI: 10.1177/19476035241276852] [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: 06/23/2024] [Revised: 08/05/2024] [Accepted: 08/06/2024] [Indexed: 09/06/2024] Open
Abstract
OBJECTIVE To assess the relation between microbiome and lipopolysaccharide (LPS), in the blood and synovial fluid (SF) with femoral cartilage thickness (FCT) measured by ultrasound (US) in knee osteoarthritis (KOA) patients. METHODS This cross-sectional study included 40 primary KOA patients recruited between September 2022 and June 2023. Age, gender, and body mass index (BMI) were recorded. Patients underwent full clinical examination, standing plain x-ray of the knee joint and knee US examination to measure medial, intercondylar, and lateral FCT. Microbiomes (specific bacterial phyla) were detected by real-time polymerase chain reaction and LPS levels were measured by enzyme-linked immunosorbent assay kit in the patients' serum and SF. RESULTS The patient's age ranged from 43 to 72 years. Most patients were females (72.5%), with a mean BMI of 35.8 ± 6.21 kg/m2. The mean medial, intercondylar, and lateral FCT were less than cut-off values. All 40 (100%) patients showed positive bacterial deoxyribonucleic acid (16S ribosomal RNA) in both blood and SF samples. Firmicutes was the most abundant in patients' blood (48.49%) and SF (63.59%). The mean serum LPS level was significantly higher compared to mean SF LPS (t =4.702, P < 0.001). There was a statistically significant negative correlation between lateral FCT and Firmicutes relative abundance in both patients' blood and SF. CONCLUSION Microbiome and LPS are present in the blood and SF of primary KOA patients. Microbiome (Firmicutes) was associated with decreased lateral FCT. This might provide a potential link between both systemic and local microbiomes and cartilage affection in KOA patients.
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Affiliation(s)
- Noha Abdelhalim Elsawy
- Department of Rheumatology, Rehabilitation and Physical Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Aya Hanafy Ibrahiem
- Department of Rheumatology, Rehabilitation and Physical Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Gihan Abdellatif Younis
- Department of Rheumatology, Rehabilitation and Physical Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Marwa Ahmed Meheissen
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Yousra Hisham Abdel-Fattah
- Department of Rheumatology, Rehabilitation and Physical Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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