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1
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El-Saadony MT, Saad AM, Mohammed DM, Korma SA, Alshahrani MY, Ahmed AE, Ibrahim EH, Salem HM, Alkafaas SS, Saif AM, Elkafas SS, Fahmy MA, Abd El-Mageed TA, Abady MM, Assal HY, El-Tarabily MK, Mathew BT, AbuQamar SF, El-Tarabily KA, Ibrahim SA. Medicinal plants: bioactive compounds, biological activities, combating multidrug-resistant microorganisms, and human health benefits - a comprehensive review. Front Immunol 2025; 16:1491777. [PMID: 40375989 PMCID: PMC12079674 DOI: 10.3389/fimmu.2025.1491777] [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: 09/05/2024] [Accepted: 03/13/2025] [Indexed: 05/18/2025] Open
Abstract
In recent years, medicinal plants have gained significant attention in modern medicine due to their accessibility, affordability, widespread acceptance, and safety, making herbal remedies highly valued globally. Consequently, ensuring medicinal plants' quality, efficacy, and safety has become a critical concern for developed and developing nations. The emergence of multidrug-resistant microorganisms poses a serious global health threat, particularly in low-income regions, despite significant advancements in antimicrobial drugs and medical research over the past century. The rapid spread of these multidrug-resistant infections is primarily attributed to improper prescriptions, overuse, and unregulated access to antibiotics. Addressing these challenges, the standardization of plant-derived pharmaceuticals could pave the way for a transformative era in healthcare. Preserving and leveraging the historical knowledge of medicinal plants is essential before such valuable information is lost. Recently, there has been growing interest among natural and pharmaceutical scientists in exploring medicinal plants as potential sources of antimicrobial agents. This current review aims to identify the most common pathogens threatening human health, analyze the factors contributing to the rise of drug-resistant microorganisms, and evaluate the widespread use of medicinal plants across various countries as alternative antibiotics, highlighting their unique mechanisms of antimicrobial resistance.
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Affiliation(s)
- Mohamed T. El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Ahmed M. Saad
- Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | | | - Sameh A. Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Mohammad Y. Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Ahmed Ezzat Ahmed
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia
| | - Essam H. Ibrahim
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia
- Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo, Egypt
| | - Heba M. Salem
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
- Department of Diseases of Birds, Rabbits, Fish & their Care & Wildlife, School of Veterinary Medicine, Badr University in Cairo (BUC), Cairo, Egypt
| | - Samar Sami Alkafaas
- Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt
| | - Abdullah M. Saif
- Division of Biochemistry, Department of Chemistry, Tanta University, Faculty of Science, Tanta, Egypt
| | - Sara Samy Elkafas
- Faculty of Control System and Robotics, Information Technologies, Mechanics and Optics University, Saint-Petersburg, Russia
- Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University, Menofia, Egypt
| | - Mohamed A. Fahmy
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Taia A. Abd El-Mageed
- Soils and Water Science Department, Faculty of Agriculture, Fayoum University, Fayoum, Egypt
| | - Mariam M. Abady
- Nutrition and Food Sciences Department, National Research Centre, Giza, Egypt
- Department of Bio-Analytical Science, University of Science and Technology, Daejeon, Republic of Korea
| | - Hanya Y. Assal
- Faculty of Biotechnology, October University for Modern Sciences and Arts, 6 October City, Egypt
| | | | - Betty T. Mathew
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Synan F. AbuQamar
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Khaled A. El-Tarabily
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Salam A. Ibrahim
- Food Microbiology and Biotechnology Laboratory, Food and Nutritional Science Program, North Carolina A&T State University, Greensboro, NC, United States
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Yang Y, Zhang Y, Zhang W, Lu K, Wang L, Liu Y, Du L, Yang J, Guan L, Ma H. Flammulina velutipes residue Polysaccharide Alleviates Immunosuppression and Intestinal Injury by Modulating Gut Microbiota and Associated Metabolites. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:7788-7806. [PMID: 40116376 DOI: 10.1021/acs.jafc.4c12105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/23/2025]
Abstract
This study elucidated the mechanisms underlying the immunoregulatory and gut-microbiota-modulating effects of Flammulina velutipes residue polysaccharide (FVRP) using cyclophosphamide (CTX)-induced mouse models. FVRP supplementation alleviated CTX-induced intestinal damage and boosted antioxidant enzyme activity and cytokine secretion. Additionally, FVRP enhanced the diversity and total species richness of the gut microbiota, promoting the proliferation of beneficial bacteria (e.g., Prevotellaceae), while reducing the abundance of CTX-derived bacteria (Lachnospiraceae and Rikenellaceae). FVRP facilitates the accumulation of short-chain fatty acids. Untargeted metabolomic analyses of cecal content revealed that FVRP treatment notably restored the levels of 32 endogenous metabolites altered by CTX. Based on a pseudosterility mice model, fecal microbiota transplantation (FMT), and fecal filtrate transplantation (FFT), gut microbiota and associated metabolites were demonstrated to play a crucial role in the immunomodulatory and protective effects of FVRP against intestinal injury. In conclusion, FVRP exhibits significant potential as an immune enhancer and natural therapeutic agent for alleviating intestinal inflammatory conditions.
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Affiliation(s)
- Yiting Yang
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Yao Zhang
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Wenying Zhang
- Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, P. R. China
| | - Kunpeng Lu
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Liping Wang
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Yanfang Liu
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Linna Du
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Jing Yang
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Lili Guan
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
| | - Hongxia Ma
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, P. R. China
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3
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Westerbeke FHM, Attaye I, Rios‐Morales M, Nieuwdorp M. Glycaemic sugar metabolism and the gut microbiota: past, present and future. FEBS J 2025; 292:1421-1436. [PMID: 39359099 PMCID: PMC11927047 DOI: 10.1111/febs.17293] [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: 10/18/2023] [Revised: 08/02/2024] [Accepted: 09/24/2024] [Indexed: 10/04/2024]
Abstract
Non-communicable diseases (NCDs), such as type 2 diabetes (T2D) and metabolic dysfunction-associated fatty liver disease, have reached epidemic proportions worldwide. The global increase in dietary sugar consumption, which is largely attributed to the production and widespread use of cheap alternatives such as high-fructose corn syrup, is a major driving factor of NCDs. Therefore, a comprehensive understanding of sugar metabolism and its impact on host health is imperative to rise to the challenge of reducing NCDs. Notably, fructose appears to exert more pronounced deleterious effects than glucose, as hepatic fructose metabolism induces de novo lipogenesis and insulin resistance through distinct mechanisms. Furthermore, recent studies have demonstrated an intricate relationship between sugar metabolism and the small intestinal microbiota (SIM). In contrast to the beneficial role of colonic microbiota in complex carbohydrate metabolism, sugar metabolism by the SIM appears to be less beneficial to the host as it can generate toxic metabolites. These fermentation products can serve as a substrate for fatty acid synthesis, imposing negative health effects on the host. Nevertheless, due to the challenging accessibility of the small intestine, our knowledge of the SIM and its involvement in sugar metabolism remains limited. This review presents an overview of the current knowledge in this field along with implications for future research, ultimately offering potential therapeutic avenues for addressing NCDs.
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Affiliation(s)
- Florine H. M. Westerbeke
- Department of Internal and Experimental Vascular MedicineAmsterdam University Medical Centers, location AMCThe Netherlands
| | - Ilias Attaye
- Department of Internal and Experimental Vascular MedicineAmsterdam University Medical Centers, location AMCThe Netherlands
| | - Melany Rios‐Morales
- Department of Internal and Experimental Vascular MedicineAmsterdam University Medical Centers, location AMCThe Netherlands
| | - Max Nieuwdorp
- Department of Internal and Experimental Vascular MedicineAmsterdam University Medical Centers, location AMCThe Netherlands
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Zhang X, Lau HCH, Yu J. Pharmacological treatment for metabolic dysfunction-associated steatotic liver disease and related disorders: Current and emerging therapeutic options. Pharmacol Rev 2025; 77:100018. [PMID: 40148030 DOI: 10.1016/j.pharmr.2024.100018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty liver disease) is a chronic liver disease affecting over a billion individuals worldwide. MASLD can gradually develop into more severe liver pathologies, including metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and liver malignancy. Notably, although being a global health problem, there are very limited therapeutic options against MASLD and its related diseases. While a thyroid hormone receptor agonist (resmetirom) is recently approved for MASH treatment, other efforts to control these diseases remain unsatisfactory. Given the projected rise in MASLD and MASH incidence, it is urgent to develop novel and effective therapeutic strategies against these prevalent liver diseases. In this article, the pathogenic mechanisms of MASLD and MASH, including insulin resistance, dysregulated nuclear receptor signaling, and genetic risk factors (eg, patatin-like phospholipase domain-containing 3 and hydroxysteroid 17-β dehydrogenase-13), are introduced. Various therapeutic interventions against MASH are then explored, including approved medication (resmetirom), drugs that are currently in clinical trials (eg, glucagon-like peptide 1 receptor agonist, fibroblast growth factor 21 analog, and PPAR agonist), and those failed in previous trials (eg, obeticholic acid and stearoyl-CoA desaturase 1 antagonist). Moreover, given that the role of gut microbes in MASLD is increasingly acknowledged, alterations in the gut microbiota and microbial mechanisms in MASLD development are elucidated. Therapeutic approaches that target the gut microbiota (eg, dietary intervention and probiotics) against MASLD and related diseases are further explored. With better understanding of the multifaceted pathogenic mechanisms, the development of innovative therapeutics that target the root causes of MASLD and MASH is greatly facilitated. The possibility of alleviating MASH and achieving better patient outcomes is within reach. SIGNIFICANCE STATEMENT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, and it can progress to more severe pathologies, including steatohepatitis, cirrhosis, and liver cancer. Better understanding of the pathogenic mechanisms of these diseases has facilitated the development of innovative therapeutic strategies. Moreover, increasing evidence has illustrated the crucial role of gut microbiota in the pathogenesis of MASLD and related diseases. It may be clinically feasible to target gut microbes to alleviate MASLD in the future.
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Affiliation(s)
- Xiang Zhang
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Harry Cheuk-Hay Lau
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jun Yu
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
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5
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Qin L, Fan B, Zhou Y, Zheng J, Diao R, Wang F, Liu J. Targeted gut microbiome therapy: Applications and prospects of probiotics, fecal microbiota transplantation and natural products in the management of type 2 diabetes. Pharmacol Res 2025; 213:107625. [PMID: 39875017 DOI: 10.1016/j.phrs.2025.107625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/21/2024] [Accepted: 01/21/2025] [Indexed: 01/30/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM. Additionally, it evaluates the potential of probiotics, fecal microbiota transplantation (FMT)/virome transplantation (FVT), and natural products in modulating gut microbiota to treat T2DM. Although existing studies have suggested that these interventions may delay or even halt the progression of T2DM, most research remained limited to animal models and observational clinical studies, with a lack of high-quality clinical data. This has led to an imbalance between theoretical research and clinical application. Although some studies have explored the regulatory role of the gut virome on the gut microbiota, research in this area remains in its early stages. Based on these current studies, future research should be focused on large-scale, long-term clinical studies and further investigation on the potential role of the gut virome in T2DM. In conclusion, this review aims to summarize the current evidence and explore the applications of gut microbiota in T2DM treatment, as well as providing recommendations for further investigation in this field.
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Affiliation(s)
- Luqi Qin
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Bei Fan
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Yixia Zhou
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Jiahuan Zheng
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Rao Diao
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Fengzhong Wang
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China.
| | - Jiameng Liu
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China.
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Byndloss M, Devkota S, Duca F, Hendrik Niess J, Nieuwdorp M, Orho-Melander M, Sanz Y, Tremaroli V, Zhao L. The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum. Diabetes Care 2024; 47:1491-1508. [PMID: 38996003 PMCID: PMC11362125 DOI: 10.2337/dci24-0052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/23/2024] [Indexed: 07/14/2024]
Abstract
This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.
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Affiliation(s)
- Mariana Byndloss
- Vanderbilt University Medical Center, Nashville, TN
- Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN
| | - Suzanne Devkota
- Human Microbiome Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | | | - Jan Hendrik Niess
- Department of Biomedicine, University of Basel, Basel, Switzerland
- Department of Gastroenterology and Hepatology, University Digestive Healthcare Center, Clarunis, Basel, Switzerland
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands
- Amsterdam Diabeter Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Marju Orho-Melander
- Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, Malmö, Sweden
| | - Yolanda Sanz
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
| | - Valentina Tremaroli
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Liping Zhao
- Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ
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Byndloss M, Devkota S, Duca F, Niess JH, Nieuwdorp M, Orho-Melander M, Sanz Y, Tremaroli V, Zhao L. The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum. Diabetologia 2024; 67:1760-1782. [PMID: 38910152 PMCID: PMC11410996 DOI: 10.1007/s00125-024-06198-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/23/2024] [Indexed: 06/25/2024]
Abstract
This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.
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Affiliation(s)
- Mariana Byndloss
- Vanderbilt University Medical Center, Nashville, TN, USA
- Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Suzanne Devkota
- Cedars-Sinai Medical Center, Human Microbiome Research Institute, Los Angeles, CA, USA
| | | | - Jan Hendrik Niess
- Department of Biomedicine, University of Basel, Basel, Switzerland
- Department of Gastroenterology and Hepatology, University Digestive Healthcare Center, Clarunis, Basel, Switzerland
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands
- Amsterdam Diabeter Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Marju Orho-Melander
- Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, Malmö, Sweden
| | - Yolanda Sanz
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain.
| | - Valentina Tremaroli
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Liping Zhao
- Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, USA
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Byndloss M, Devkota S, Duca F, Niess JH, Nieuwdorp M, Orho-Melander M, Sanz Y, Tremaroli V, Zhao L. The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum. Diabetes 2024; 73:1391-1410. [PMID: 38912690 PMCID: PMC11333376 DOI: 10.2337/dbi24-0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/23/2024] [Indexed: 06/25/2024]
Abstract
This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.
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Affiliation(s)
- Mariana Byndloss
- Vanderbilt University Medical Center, Nashville, TN
- Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN
| | - Suzanne Devkota
- Human Microbiome Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | | | - Jan Hendrik Niess
- Department of Biomedicine, University of Basel, Basel, Switzerland
- Department of Gastroenterology and Hepatology, University Digestive Healthcare Center, Clarunis, Basel, Switzerland
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands
- Amsterdam Diabeter Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Marju Orho-Melander
- Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, Malmö, Sweden
| | - Yolanda Sanz
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
| | - Valentina Tremaroli
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Liping Zhao
- Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ
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Soueges S, Cheynet V, Briot T, Merveilleux du Vignaux C, Benech N, Ader F. Clinical remission after faecal microbiota transplantation in transplanted recipients with refractory chronic Norovirus infections: a retrospective case series. Clin Microbiol Infect 2024; 30:1083-1085. [PMID: 38697391 DOI: 10.1016/j.cmi.2024.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/09/2024] [Accepted: 04/22/2024] [Indexed: 05/05/2024]
Affiliation(s)
- Sarah Soueges
- Départment des Maladies Infectieuses et tropicales, Hospices Civils de Lyon, F-69004, Lyon, France.
| | - Valérie Cheynet
- Laboratoire commun de Recherche des Hospices Civils de Lyon-bioMérieux, Pierre-Bénite, France
| | - Thomas Briot
- Département de Pharmacie, Hospices Civils de Lyon, F-69004, Lyon, France; French Fecal Transplant Group, France
| | | | - Nicolas Benech
- French Fecal Transplant Group, France; Hospices civils de Lyon, Service d'Hépato-Gastroentérologie, F-69003, Lyon, France; Claude Bernard Lyon 1 University, CRCL, Lyon, France; Lyon GEM Groupe d'étude du microbiote, Lyon, France
| | - Florence Ader
- Départment des Maladies Infectieuses et tropicales, Hospices Civils de Lyon, F-69004, Lyon, France; French Fecal Transplant Group, France; Lyon GEM Groupe d'étude du microbiote, Lyon, France; Centre International de Recherche en Infectiologie, Inserm 1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, F-69007, France
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10
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Sahle Z, Engidaye G, Shenkute Gebreyes D, Adenew B, Abebe TA. Fecal microbiota transplantation and next-generation therapies: A review on targeting dysbiosis in metabolic disorders and beyond. SAGE Open Med 2024; 12:20503121241257486. [PMID: 38826830 PMCID: PMC11143861 DOI: 10.1177/20503121241257486] [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: 09/15/2023] [Accepted: 05/09/2024] [Indexed: 06/04/2024] Open
Abstract
The human microbiome, particularly the gut microbiome, has emerged as a central determinant of health and disease. Dysbiosis, an imbalance in the microbial composition of the gut, is associated with a variety of metabolic and other diseases, highlighting the potential for microbiota-targeted treatments. Fecal microbiota transplantation has received considerable attention as a promising therapy to modulate the gut microbiome and restore microbial homeostasis. However, challenges remain, including standardization, safety, and long-term efficacy. This review summarizes current knowledge on fecal microbiota transplantation and describes the next generation therapies targeting microbiome. This review looked at the mechanistic understanding of fecal microbiota transplantation and alternative strategies, elucidating their potential role in improving dysbiosis-associated metabolic disorders, such as obesity, and type 2 diabetes and others. Additionally, this review discussed the growing application of therapies targeting the gut microbiome. Insights from clinical trials, preclinical studies, and emerging technologies provide a comprehensive overview of the evolving landscape of microbiome-based interventions. Through a critical assessment of current advances and prospects, this review aims to highlight the therapeutic potential of targeting gut microbiome and pave the way for innovative approaches in precision medicine and personalized treatments.
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Affiliation(s)
- Zenawork Sahle
- Department of Medical Laboratory Science, Asrat Weldeyes Health Science Campus, Debre Berhan University, Debre Berhan, Ethiopia
| | - Getabalew Engidaye
- Department of Medical Laboratory Science, Asrat Weldeyes Health Science Campus, Debre Berhan University, Debre Berhan, Ethiopia
| | - Demissew Shenkute Gebreyes
- Department of Medical Laboratory Science, Asrat Weldeyes Health Science Campus, Debre Berhan University, Debre Berhan, Ethiopia
| | - Behailu Adenew
- Department of Medical Laboratory Science, Debre Berhan Compressive Specialized Hospital, Debre Berhan, Ethiopia
| | - Tsegahun Asfaw Abebe
- Department of Medical Laboratory Science, Asrat Weldeyes Health Science Campus, Debre Berhan University, Debre Berhan, Ethiopia
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11
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Andary CM, Al KF, Chmiel JA, Gibbons S, Daisley BA, Parvathy SN, Maleki Vareki S, Bowdish DME, Silverman MS, Burton JP. Dissecting mechanisms of fecal microbiota transplantation efficacy in disease. Trends Mol Med 2024; 30:209-222. [PMID: 38195358 DOI: 10.1016/j.molmed.2023.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 12/06/2023] [Accepted: 12/11/2023] [Indexed: 01/11/2024]
Abstract
Fecal microbiota transplantation (FMT) has emerged as an alternative or adjunct experimental therapy for microbiome-associated diseases following its success in the treatment of recurrent Clostridioides difficile infections (rCDIs). However, the mechanisms of action involved remain relatively unknown. The term 'dysbiosis' has been used to describe microbial imbalances in relation to disease, but this traditional definition fails to consider the complex cross-feeding networks that define the stability of the microbiome. Emerging research transitions toward the targeted restoration of microbial functional networks in treating different diseases. In this review, we explore potential mechanisms responsible for the efficacy of FMT and future therapeutic applications, while revisiting definitions of 'dysbiosis' in favor of functional network restoration in rCDI, inflammatory bowel diseases (IBDs), metabolic diseases, and cancer.
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Affiliation(s)
- Catherine M Andary
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Kait F Al
- Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics Research, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada
| | - John A Chmiel
- Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics Research, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada
| | - Shaeley Gibbons
- Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics Research, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada
| | - Brendan A Daisley
- Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
| | - Seema Nair Parvathy
- Division of Infectious Disease, St. Joseph's Health Care, London, Ontario, Canada
| | - Saman Maleki Vareki
- Lawson Health Research Institute, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
| | - Dawn M E Bowdish
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre and the Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada
| | - Michael S Silverman
- Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Division of Infectious Disease, St. Joseph's Health Care, London, Ontario, Canada
| | - Jeremy P Burton
- Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics Research, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Department of Surgery, Western University, London, Ontario, Canada.
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12
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Kong F, Wang F, Zhang Y, Wang S, Wang W, Li S. Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows. J Anim Sci Biotechnol 2024; 15:17. [PMID: 38310317 PMCID: PMC10838461 DOI: 10.1186/s40104-023-00963-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 12/01/2023] [Indexed: 02/05/2024] Open
Abstract
BACKGROUND The dairy cow's postpartum period is characterized by dramatic physiological changes, therefore imposing severe challenges on the animal for maintaining health and milk output. The dynamics of the ruminal microbiota are also tremendous and may play a crucial role in lactation launch. We aim to investigate the potential benefits of early microbial intervention by fresh rumen microbiota transplantation (RMT) and sterile RMT in postpartum dairy cows. Twelve fistulated peak-lactation dairy cows were selected to be the donors for rumen fluid collection. Thirty postpartum cows were divided into 3 groups as the transplantation receptors respectively receiving 10 L fresh rumen fluid (FR), 10 L sterile rumen fluid (SR), or 10 L saline (CON) during 3 d after calving. RESULTS Production performance, plasma indices, plasma lipidome, ruminal microbiome, and liver transcriptome were recorded. After fresh and sterile RMT, we found that the molar proportion of propionic acid was increased on d 7 in the FR and SR groups and the bacterial composition was also significantly changed when compared with the CON group. A similarity analysis showed that the similarities between the CON group and FR or SR group on d 7 were 48.40% or 47.85%, whereas the similarities between microbiota on d 7 and 21 in the FR and SR groups were 68.34% or 66.85%. Dry matter intake and feed efficiency were not affected by treatments. Plasma β-hydroxybutyrate concentration in the FR group was decreased and significantly different lipids mainly included phosphatidylcholine and lysophosphatidylcholine containing polyunsaturated fatty acids. Hepatic transcriptomics analysis indicated acute-phase response pathways were upregulated in the SR group. CONCLUSIONS Our study suggests that RMT can shorten the transition process of the ruminal microbiota of postpartum dairy cows with no benefit on dry matter intake or feed efficiency. Inoculation with rumen fluid may not be a useful approach to promote the recovery of postpartum dairy cows.
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Affiliation(s)
- Fanlin Kong
- Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China
| | - Feiran Wang
- Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China
| | - Yijia Zhang
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Shuo Wang
- Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China
| | - Wei Wang
- Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
| | - Shengli Li
- Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
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Bourragat A, Escoula Q, Bellenger S, Zemb O, Beaumont M, Chaumonnot K, Farine JP, Jacotot E, Bonnotte A, Avoscan L, Lherminier J, Luo K, Narce M, Bellenger J. The transplantation of the gut microbiome of fat-1 mice protects against colonic mucus layer disruption and endoplasmic reticulum stress induced by high fat diet. Gut Microbes 2024; 16:2356270. [PMID: 38797998 PMCID: PMC11135845 DOI: 10.1080/19490976.2024.2356270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 05/13/2024] [Indexed: 05/29/2024] Open
Abstract
High-fat diets alter gut barrier integrity, leading to endotoxemia by impacting epithelial functions and inducing endoplasmic reticulum (ER) stress in intestinal secretory goblet cells. Indeed, ER stress, which is an important contributor to many chronic diseases such as obesity and obesity-related disorders, leads to altered synthesis and secretion of mucins that form the protective mucus barrier. In the present study, we investigated the relative contribution of omega-3 polyunsaturated fatty acid (PUFAs)-modified microbiota to alleviating alterations in intestinal mucus layer thickness and preserving gut barrier integrity. Male fat-1 transgenic mice (exhibiting endogenous omega-3 PUFAs tissue enrichment) and wild-type (WT) littermates were fed either an obesogenic high-fat diet (HFD) or a control diet. Unlike WT mice, HFD-fed fat-1 mice were protected against mucus layer alterations as well as an ER stress-mediated decrease in mucin expression. Moreover, cecal microbiota transferred from fat-1 to WT mice prevented changes in the colonic mucus layer mainly through colonic ER stress downregulation. These findings highlight a novel feature of the preventive effects of omega-3 fatty acids against intestinal permeability in obesity-related conditions.
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Affiliation(s)
- Amina Bourragat
- CTM UMR1231, Université de Bourgogne, Dijon, France
- CTM UMR1231, INSERM, Dijon, France
- LipSTIC LabEx, FCS Bourgogne-Franche Comté, Dijon, France
| | - Quentin Escoula
- CTM UMR1231, Université de Bourgogne, Dijon, France
- CTM UMR1231, INSERM, Dijon, France
- LipSTIC LabEx, FCS Bourgogne-Franche Comté, Dijon, France
- Valorex, La Messayais, Combourtillé, France
| | - Sandrine Bellenger
- CTM UMR1231, Université de Bourgogne, Dijon, France
- CTM UMR1231, INSERM, Dijon, France
- LipSTIC LabEx, FCS Bourgogne-Franche Comté, Dijon, France
| | - Olivier Zemb
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
| | - Martin Beaumont
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
| | - Killian Chaumonnot
- CTM UMR1231, Université de Bourgogne, Dijon, France
- CTM UMR1231, INSERM, Dijon, France
| | - Jean-Pierre Farine
- Centre des Sciences du Goût et de l’Alimentation, UMR6265 CNRS, UMR1324 INRA, Université de Bourgogne, Dijon, France
| | - Emmanuel Jacotot
- L’Institut Agro Dijon, PAM UMR A 02.102, Université de Bourgogne, Dijon, France
| | - Aline Bonnotte
- Agroécologie, L’Institut Agro Dijon, CNRS, INRAE, Plateforme DimaCell, Dijon, France
| | - Laure Avoscan
- Agroécologie, L’Institut Agro Dijon, CNRS, INRAE, Plateforme DimaCell, Dijon, France
| | - Jeanine Lherminier
- Agroécologie, L’Institut Agro Dijon, CNRS, INRAE, Plateforme DimaCell, Dijon, France
| | - Kangjia Luo
- CTM UMR1231, Université de Bourgogne, Dijon, France
- CTM UMR1231, INSERM, Dijon, France
- LipSTIC LabEx, FCS Bourgogne-Franche Comté, Dijon, France
| | - Michel Narce
- CTM UMR1231, Université de Bourgogne, Dijon, France
- CTM UMR1231, INSERM, Dijon, France
- LipSTIC LabEx, FCS Bourgogne-Franche Comté, Dijon, France
| | - Jérôme Bellenger
- CTM UMR1231, Université de Bourgogne, Dijon, France
- CTM UMR1231, INSERM, Dijon, France
- LipSTIC LabEx, FCS Bourgogne-Franche Comté, Dijon, France
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Goldsmith J, Tomkovich S, Auniņš JG, McGovern BH, Mahoney JC, Hasson BR, McChalicher CWJ, Ege DS. End-to-end donor screening and manufacturing controls: complementary quality-based strategies to minimize patient risk for donor-derived microbiome therapeutics. Gut Microbes 2024; 16:2402550. [PMID: 39292598 PMCID: PMC11529408 DOI: 10.1080/19490976.2024.2402550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/26/2024] [Accepted: 09/04/2024] [Indexed: 09/20/2024] Open
Abstract
Advances in microbiome therapeutics have been motivated by a deeper understanding of the role that the gastrointestinal microbiome plays in human health and disease. The FDA approval of two stool-derived live biotherapeutic products (LBPs), REBYOTA® 150 mL enema (fecal microbiota, live-jslm; formerly RBX2660) and VOWST® oral capsules (fecal microbiota spores, live-brpk; formerly SER-109), for the prevention of recurrent CDI in adults following antibiotic treatment for recurrent CDI provides promise and insights for the development of LBPs for other diseases associated with microbiome dysfunction. Donor-derived products carry risk of disease transmission that must be mitigated through a robust donor screening program and downstream manufacturing controls. Most published recommendations for donor screening practices are prescriptive and do not include a systematic, risk-based approach for donor stool-derived products. A general framework for an end-to-end donor screening program is needed using risk management strategies for donor-derived microbiome therapeutic using a matrixed approach, combining the elements of donor screening with manufacturing controls that are designed to minimize risk to patients. A donor screening paradigm that incorporates medical history, physical examination, laboratory testing, and donor sample inspection are only the first steps in reducing risk of transmission of infectious agents. Manufacturing controls are the cornerstone of risk mitigation when screening unwittingly fails. Failure Mode and Effects Analysis (FMEA) can be used as a tool to assess for residual risk that requires further donor or manufacturing controls. Together, a well-reasoned donor program and manufacturing controls are complementary strategies that must be revisited and reexamined frequently with constant vigilance to mitigate risk to patients. In the spirit of full disclosure and informed consent, physicians should discuss any limitations in the donor screening and manufacturing processes with their patients prior to treatment with microbiome-based therapeutics.
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Affiliation(s)
- Jason Goldsmith
- Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA
| | - Sarah Tomkovich
- Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA
| | - John G. Auniņš
- Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA
| | - Barbara H. McGovern
- Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA
| | - Jennifer C. Mahoney
- Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA
| | - Brooke R. Hasson
- Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA
| | | | - David S. Ege
- Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA
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Yu Y, Wang W, Zhang F. The Next Generation Fecal Microbiota Transplantation: To Transplant Bacteria or Virome. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2301097. [PMID: 37914662 PMCID: PMC10724401 DOI: 10.1002/advs.202301097] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 09/02/2023] [Indexed: 11/03/2023]
Abstract
Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for dysbiosis-related diseases. However, the clinical practice of crude fecal transplants presents limitations in terms of acceptability and reproductivity. Consequently, two alternative solutions to FMT are developed: transplanting bacteria communities or virome. Advanced methods for transplanting bacteria mainly include washed microbiota transplantation and bacteria spores treatment. Transplanting the virome is also explored, with the development of fecal virome transplantation, which involves filtering the virome from feces. These approaches provide more palatable options for patients and healthcare providers while minimizing research heterogeneity. In general, the evolution of the next generation of FMT in global trends is fecal microbiota components transplantation which mainly focuses on transplanting bacteria or virome.
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Affiliation(s)
- You Yu
- Department of Microbiota Medicine & Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
| | - Weihong Wang
- Department of Microbiota Medicine & Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
| | - Faming Zhang
- Department of Microbiota Medicine & Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
- Department of Microbiota MedicineSir Run Run HospitalNanjing Medical UniversityNanjing211166China
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16
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Diwan B, Yadav R, Singh A, Kumar D, Sharma R. Murine sterile fecal filtrate is a potent pharmacological agent that exerts age-independent immunomodulatory effects in RAW264.7 macrophages. BMC Complement Med Ther 2023; 23:362. [PMID: 37833682 PMCID: PMC10576334 DOI: 10.1186/s12906-023-04193-4] [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: 03/04/2023] [Accepted: 10/03/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Sterile fecal filtrate (SFF) is being considered a safer alternative to fecal microbiota transplantation (FMT) therapy; however, its bioactive potency is very little understood. The present study thus assessed the age-dependent immunostimulatory and immunomodulatory attributes of murine SFF in vitro. METHODS SFF from young (Y-SFF) and old (O-SFF) Swiss albino mice were prepared. Immunostimulatory and immunomodulatory effects of SFF were evaluated in resting and lipopolysaccharide (LPS) stimulated macrophage cells by measuring intracellular reactive oxygen species (ROS), nitric oxide (NO) production, inflammatory cytokines profile, as well as gene expression of oxidative and inflammatory transcription factors. SFF were also evaluated for native antioxidant capacity by measuring DPPH and ABTS free radical scavenging activity. Bioactive components present in SFF were also determined by GC/MS analysis. RESULTS Both Y-SFF and O-SFF induced potent immunostimulatory effects characterized by changes in cell morphology, a significant increase in NO production, ROS levels, and an increased ratio of pro-inflammatory (IL-6, TNF-α, IL-1β) to anti-inflammatory (IL-10) secretory proteins although no significant aggravation in the transcription of NF-κB and Nrf-2 could be observed. Application of LPS to cells significantly augmented a pro-oxidative and pro-inflammatory response which was much higher in comparison to Y-SFF or O-SFF application alone and mediated by strong suppression of Nrf-2 gene expression. Pre-treatment of macrophages with both Y-SFF and O-SFF robustly attenuated cellular hyperresponsiveness to LPS characterized by significantly decreased levels of NO, ROS, and inflammatory cytokines while a concomitant increase in anti-inflammatory protein (IL-10) was observed. Further, both Y-SFF and O-SFF strongly resisted LPS-induced downregulation of Nrf-2 expression although O-SFF appeared to protect cells slightly better from the overall LPS threat. Neat SFF samples exhibited moderate antioxidant capacity and GC/MS analysis of SFF revealed diverse volatile organic compounds characterized by alkanes, organosulphur compounds, furans, amides, amino acids, and antimicrobial elements. CONCLUSION Our results indicate that SFF is a potent stimulant of macrophages and confers strong anti-inflammatory effects regardless of donor age thereby suggesting its therapeutic efficacy in lieu of FMT therapy.
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Affiliation(s)
- Bhawna Diwan
- Faculty of Applied Sciences & Biotechnology, Shoolini University, Solan, 173229, India
| | - Rahul Yadav
- Faculty of Applied Sciences & Biotechnology, Shoolini University, Solan, 173229, India
| | - Anamika Singh
- Faculty of Applied Sciences & Biotechnology, Shoolini University, Solan, 173229, India
| | - Dinesh Kumar
- Faculty of Applied Sciences & Biotechnology, Shoolini University, Solan, 173229, India
| | - Rohit Sharma
- Faculty of Applied Sciences & Biotechnology, Shoolini University, Solan, 173229, India.
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17
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Zhang Y, Sharma S, Tom L, Liao YT, Wu VCH. Gut Phageome-An Insight into the Role and Impact of Gut Microbiome and Their Correlation with Mammal Health and Diseases. Microorganisms 2023; 11:2454. [PMID: 37894111 PMCID: PMC10609124 DOI: 10.3390/microorganisms11102454] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 09/25/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
The gut microbiota, including bacteria, archaea, fungi, and viruses, compose a diverse mammalian gut environment and are highly associated with host health. Bacteriophages, the viruses that infect bacteria, are the primary members of the gastrointestinal virome, known as the phageome. However, our knowledge regarding the gut phageome remains poorly understood. In this review, the critical role of the gut phageome and its correlation with mammalian health were summarized. First, an overall profile of phages across the gastrointestinal tract and their dynamic roles in shaping the surrounding microorganisms was elucidated. Further, the impacts of the gut phageome on gastrointestinal fitness and the bacterial community were highlighted, together with the influence of diets on the gut phageome composition. Additionally, new reports on the role of the gut phageome in the association of mammalian health and diseases were reviewed. Finally, a comprehensive update regarding the advanced phage benchwork and contributions of phage-based therapy to prevent/treat mammalian diseases was provided. This study provides insights into the role and impact of the gut phagenome in gut environments closely related to mammal health and diseases. The findings provoke the potential applications of phage-based diagnosis and therapy in clinical and agricultural fields. Future research is needed to uncover the underlying mechanism of phage-bacterial interactions in gut environments and explore the maintenance of mammalian health via phage-regulated gut microbiota.
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Affiliation(s)
| | | | | | | | - Vivian C. H. Wu
- Produce Safety and Microbiology Research Unit, U.S. Department of Agriculture, Agricultural Research Service, Western Regional Research Center, Albany, CA 94710, USA
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18
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Hoskinson C, Jiang RY, Stiemsma LT. Elucidating the roles of the mammary and gut microbiomes in breast cancer development. Front Oncol 2023; 13:1198259. [PMID: 37664075 PMCID: PMC10470065 DOI: 10.3389/fonc.2023.1198259] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 07/26/2023] [Indexed: 09/05/2023] Open
Abstract
The mammary microbiome is a newly characterized bacterial niche that might offer biological insight into the development of breast cancer. Together with in-depth analysis of the gut microbiome in breast cancer, current evidence using next-generation sequencing and metabolic profiling suggests compositional and functional shifts in microbial consortia are associated with breast cancer. In this review, we discuss the fundamental studies that have progressed this important area of research, focusing on the roles of both the mammary tissue microbiome and the gut microbiome. From the literature, we identified the following major conclusions, (I) There are unique breast and gut microbial signatures (both compositional and functional) that are associated with breast cancer, (II) breast and gut microbiome compositional and breast functional dysbiosis represent potential early events of breast tumor development, (III) specific breast and gut microbes confer host immune responses that can combat breast tumor development and progression, and (IV) chemotherapies alter the microbiome and thus maintenance of a eubiotic microbiome may be key in breast cancer treatment. As the field expectantly advances, it is necessary for the role of the microbiome to continue to be elucidated using multi-omic approaches and translational animal models in order to improve predictive, preventive, and therapeutic strategies for breast cancer.
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Affiliation(s)
- Courtney Hoskinson
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
| | | | - Leah T. Stiemsma
- Natural Science Division, Pepperdine University, Malibu, CA, United States
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19
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Jabri H, Krings S, Fall PA, Baurain D, Daube G, Taminiau B. Microbiota Profiling on Veterinary Faculty Restroom Surfaces and Source Tracking. Microorganisms 2023; 11:2053. [PMID: 37630613 PMCID: PMC10459056 DOI: 10.3390/microorganisms11082053] [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: 07/10/2023] [Revised: 08/02/2023] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
In this study, we aimed to develop a comprehensive microbial source amplicon database tailored for source tracking in veterinary settings. We rigorously tested our locally curated source tracking database by selecting a frequently accessed environment by veterinary students and veterinarians. By exploring the composition of resident microbiota and identifying potential sources of contamination, including animals, the environment, and human beings, we aimed to provide valuable insights into the dynamics of microbial transmission within veterinary facilities. The 16S rDNA amplicon sequencing was used to determine the bacterial taxonomic profiles of restroom surfaces. Bacterial sources were identified by linking our metadata-enriched local database to the microbiota profiling analysis using high-quality sequences. Microbiota profiling shows the dominance of four phyla: Actinobacteria, Bacteroidetes, Proteobacteria, and Firmicutes. If the restroom cleaning process did not appear to impact microbiota composition, significant differences regarding bacterial distribution were observed between male and female users in different sampling campaigns. Combining 16S rDNA profiling to our specific sources labeling pipeline, we found aquatic and human sources were the primary environment keywords in our campaigns. The probable presence of known animal sources (bovids, insects, equids, suids…) associated with bacterial genera such as Chryseobacterium, Bergeyella, Fibrobacter, and Syntrophococcus was also involved in restroom surfaces, emphasizing the proximity between these restrooms and the exchange of bacteria between people involved in animals handling. To summarize, we have demonstrated that DNA sequence-based source tracking may be integrated with high-throughput bacterial community analysis to enrich microbial investigation of potential bacterial contamination sources, especially for little known or poorly identified taxa. However, more research is needed to determine the tool's utility in other applications.
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Affiliation(s)
- Hiba Jabri
- Laboratory of Food Microbiology, Fundamental and Applied Research for Animals and Health Center (FARAH), Department of Food Sciences, Faculty of Veterinary Medicine, University of Liege, Quartier Vallée 2, B42, Avenue de Cureghem 10, 4000 Liège, Belgium; (H.J.); (G.D.)
| | - Simone Krings
- Department of Microbial Sciences, School of Biosciences, Faculty of Health and Medical Sciences, Univesity of Surrey, Guildford GU2 7XH, UK;
| | - Papa Abdoulaye Fall
- FoodChainID GENOMICS, Laboratory Manager NGS, Rue Hayeneux, 62, 4040 Herstal, Belgium;
| | - Denis Baurain
- Eukaryotic Phylogenomics, InBioS-PhytoSYSTEMS, University of Liège, 4000 Liège, Belgium;
| | - Georges Daube
- Laboratory of Food Microbiology, Fundamental and Applied Research for Animals and Health Center (FARAH), Department of Food Sciences, Faculty of Veterinary Medicine, University of Liege, Quartier Vallée 2, B42, Avenue de Cureghem 10, 4000 Liège, Belgium; (H.J.); (G.D.)
| | - Bernard Taminiau
- Laboratory of Food Microbiology, Fundamental and Applied Research for Animals and Health Center (FARAH), Department of Food Sciences, Faculty of Veterinary Medicine, University of Liege, Quartier Vallée 2, B42, Avenue de Cureghem 10, 4000 Liège, Belgium; (H.J.); (G.D.)
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20
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Kriger-Sharabi O, Malnick SDH, Fisher D. Manipulation of the intestinal microbiome-a slow journey to primetime. World J Clin Cases 2023; 11:4975-4988. [PMID: 37583860 PMCID: PMC10424025 DOI: 10.12998/wjcc.v11.i21.4975] [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: 03/23/2023] [Revised: 05/17/2023] [Accepted: 06/30/2023] [Indexed: 07/26/2023] Open
Abstract
The gut microbiota has important functions in the regulation of normal body functions. Alterations of the microbiota are being increasingly linked to various disease states. The microbiome has been manipulated via the administration of stool from animals or humans, for more than 1000 years. Currently, fecal microbiota transplantation can be performed via endoscopic administration of fecal matter to the duodenum or colon or via capsules of lyophilized stools. More recently fecal microbial transplantation has been shown to be very effective for recurrent Clostridoides difficile infection (CDI). In addition there is some evidence of efficacy in the metabolic syndrome and its hepatic manifestation, metabolic associated fatty liver disease (MAFLD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We review the current literature regarding the microbiome and the pathogenesis and treatment of CDI, MAFLD, IBS and IBD.
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Affiliation(s)
- Ofra Kriger-Sharabi
- Institute of Gastroenterology, Assuta Medical Center, Ashdod 7747629, Israel
| | - Stephen D H Malnick
- Department of Internal Medicine, Kaplan Medical Center, Rehovot 76100, Israel
| | - David Fisher
- Department of Endocrinology, Soroka Medical Center, Beer Sheva POB 151, Israel
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21
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Dallas JW, Warne RW. Captivity and Animal Microbiomes: Potential Roles of Microbiota for Influencing Animal Conservation. MICROBIAL ECOLOGY 2023; 85:820-838. [PMID: 35316343 DOI: 10.1007/s00248-022-01991-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 03/07/2022] [Indexed: 05/04/2023]
Abstract
During the ongoing biodiversity crisis, captive conservation and breeding programs offer a refuge for species to persist and provide source populations for reintroduction efforts. Unfortunately, captive animals are at a higher disease risk and reintroduction efforts remain largely unsuccessful. One potential factor in these outcomes is the host microbiota which includes a large diversity and abundance of bacteria, fungi, and viruses that play an essential role in host physiology. Relative to wild populations, the generalized pattern of gut and skin microbiomes in captivity are reduced alpha diversity and they exhibit a significant shift in community composition and/or structure which often correlates with various physiological maladies. Many conditions of captivity (antibiotic exposure, altered diet composition, homogenous environment, increased stress, and altered intraspecific interactions) likely lead to changes in the host-associated microbiome. To minimize the problems arising from captivity, efforts can be taken to manipulate microbial diversity and composition to be comparable with wild populations through methods such as increasing dietary diversity, exposure to natural environmental reservoirs, or probiotics. For individuals destined for reintroduction, these strategies can prime the microbiota to buffer against novel pathogens and changes in diet and improve reintroduction success. The microbiome is a critical component of animal physiology and its role in species conservation should be expanded and included in the repertoire of future management practices.
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Affiliation(s)
- Jason W Dallas
- Department of Biological Sciences, Southern Illinois University, 1125 Lincoln Drive, Carbondale, IL, 62901, USA.
| | - Robin W Warne
- Department of Biological Sciences, Southern Illinois University, 1125 Lincoln Drive, Carbondale, IL, 62901, USA
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22
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English J, Patrick S, Stewart LD. The potential role of molecular mimicry by the anaerobic microbiome in the aetiology of autoimmune disease. Anaerobe 2023; 80:102721. [PMID: 36940867 DOI: 10.1016/j.anaerobe.2023.102721] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 02/28/2023] [Accepted: 03/13/2023] [Indexed: 03/23/2023]
Abstract
Autoimmune diseases are thought to develop as a consequence of various environmental and genetic factors, each of which contributes to dysfunctional immune responses and/or a breakdown in immunological tolerance towards native structures. Molecular mimicry by microbial components is among the environmental factors thought to promote a breakdown in immune tolerance, particularly through the presence of cross-reactive epitopes shared with the human host. While resident members of the microbiome are essential promoters of human health through immunomodulation, defence against pathogenic colonisation and conversion of dietary fibre into nutritional resources for host tissues, there may be an underappreciated role of these microbes in the aetiology and/or progression of autoimmune disease. An increasing number of molecular mimics are being identified amongst the anaerobic microbiota which structurally resemble endogenous components and, in some cases, for example the human ubiquitin mimic of Bacteroides fragilis and DNA methyltransferase of Roseburia intestinalis, have been associated with promoting antibody profiles characteristic of autoimmune diseases. The persistent exposure of molecular mimics from the microbiota to the human immune system is likely to be involved in autoantibody production that contributes to the pathologies associated with immune-mediated inflammatory disorders. Here-in, examples of molecular mimics that have been identified among resident members of the human microbiome and their ability to induce autoimmune disease through cross-reactive autoantibody production are discussed. Improved awareness of the molecular mimics that exist among human colonisers will help elucidate the mechanisms involved in the breakdown of immune tolerance that ultimately lead to chronic inflammation and downstream disease.
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Affiliation(s)
- Jamie English
- Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast. 19 Chlorine Gardens, Belfast, BT9 5DL, UK
| | - Sheila Patrick
- Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast. 19 Chlorine Gardens, Belfast, BT9 5DL, UK; The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Linda D Stewart
- Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast. 19 Chlorine Gardens, Belfast, BT9 5DL, UK.
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23
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Research Progress of Fecal Microbiota Transplantation in Liver Diseases. J Clin Med 2023; 12:jcm12041683. [PMID: 36836218 PMCID: PMC9960958 DOI: 10.3390/jcm12041683] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/06/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
A growing body of evidence suggested that gut microbiota is associated with liver diseases through the gut-liver axis. The imbalance of gut microbiota could be correlated with the occurrence, development, and prognosis of a series of liver diseases, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC). Fecal microbiota transplantation (FMT) seems to be a method to normalize the patient's gut microbiota. This method has been traced back to the 4th century. In recent decade, FMT has been highly regarded in several clinical trials. As a novel approach to reconstruct the intestinal microecological balance, FMT has been used to treat the chronic liver diseases. Therefore, in this review, the role of FMT in the treatment of liver diseases was summarized. In addition, the relationship between gut and liver was explored through the gut-liver axis, and the definition, objectives, advantages, and procedures of FMT were described. Finally, the clinical value of FMT therapy in liver transplant (LT) recipients was briefly discussed.
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24
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Wang C, Bai J, Chen X, Song J, Zhang Y, Wang H, Suo H. Gut microbiome-based strategies for host health and disease. Crit Rev Food Sci Nutr 2023; 64:6834-6849. [PMID: 36803092 DOI: 10.1080/10408398.2023.2176464] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Host health and disease are influenced by changes in the abundance and structure of intestinal flora. Current strategies are focused on regulating the structure of intestinal flora to ensure host health by alleviating disease. However, these strategies are limited by multiple factors, such as host genotype, physiology (microbiome, immunity, and gender), intervention, and diet. Accordingly, we reviewed the prospects and limitations of all strategies regulating the structure and abundance of microflora, including probiotics, prebiotics, diet, fecal microbiota transplantation, antibiotics, and phages. Some new technologies that can improve these strategies are also introduced. Compared with other strategies, diets and prebiotics are associated with reduced risk and high security. Besides, phages have the potential for application in the targeted regulation of intestinal microbiota due to their high specificity. Notably, the variability in individual microflora and their metabolic response to different interventions should be considered. Future studies should use artificial intelligence combined with multi-omics to investigate the host genome and physiology based on factors, such as blood type, dietary habits, and exercise, in order to develop individualized intervention strategies to improve host health.
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Affiliation(s)
- Chen Wang
- College of Food Science, Southwest University, Chongqing, China
| | - Junying Bai
- Citrus Research Institute, National Citrus Engineering Research Center, Southwest University, Chongqing, China
| | - Xiaoyong Chen
- College of Food Science, Southwest University, Chongqing, China
| | - Jiajia Song
- College of Food Science, Southwest University, Chongqing, China
| | - Yu Zhang
- College of Food Science, Southwest University, Chongqing, China
| | - Hongwei Wang
- College of Food Science, Southwest University, Chongqing, China
| | - Huayi Suo
- College of Food Science, Southwest University, Chongqing, China
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25
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Thacher PR, Kendrick EL, Maslanka M, Muletz-Wolz CR, Bornbusch SL. Fecal microbiota transplants modulate the gut microbiome of a two-toed sloth (Choloepus didactylus). Zoo Biol 2023; 42:453-458. [PMID: 36629092 DOI: 10.1002/zoo.21751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 11/18/2022] [Accepted: 12/23/2022] [Indexed: 01/12/2023]
Abstract
The microbes inhabiting an animal's gastrointestinal tracts, collectively known as the gut microbiome, are vital to animal health and wellbeing. For animals experiencing gut distress or infection, modulation of the gut microbiome, for example, via fecal microbiota transplant (FMT), provides a possible disease prevention and treatment method. The beneficial microbes present in the donor's transplanted feces can help combat pathogens, assist in digestion, and rebalance the recipient's microbiota. Investigating the efficacy of FMTs in animal health is a crucial step toward improving management strategies for species under human care. We present a case study of the use of FMTs in a two-toed sloth experiencing abnormally large, clumped, and frequent stools. We used 16 S rRNA amplicon sequencing of fecal samples to (a) compare the microbiomes of the FMT donor, a healthy, cohoused conspecific, and the FMT recipient and (b) assess the influence of multiple rounds of FMTs on the recipient's microbiome and stool consistency and frequency over time. In response to the FMTs, we found that the recipient's microbiome showed trends toward increased diversity, shifted community composition, and altered membership that more resembled the community of the donor. FMT treatment was also associated with marked, yet temporary, alleviation of the recipient's abnormal bowel movements, suggesting a broader impact on gut health. Our results provide valuable preliminary evidence that FMT treatments can augment the recipient's gut microbiome, with potential implications for animal health and management.
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Affiliation(s)
- Piper R Thacher
- Center for Conservation Genomics, Smithsonian's National Zoo and Conservation Biology Institute, Washington, District of Columbia, USA.,Department of Environmental Science and Policy, Smithsonian Mason School of Conservation, George Mason University, Fairfax, Virginia, USA
| | - Erin L Kendrick
- Department of Nutrition Science, Smithsonian's National Zoo and Conservation Biology Institute, Washington, District of Columbia, USA
| | - Michael Maslanka
- Department of Nutrition Science, Smithsonian's National Zoo and Conservation Biology Institute, Washington, District of Columbia, USA
| | - Carly R Muletz-Wolz
- Center for Conservation Genomics, Smithsonian's National Zoo and Conservation Biology Institute, Washington, District of Columbia, USA
| | - Sally L Bornbusch
- Center for Conservation Genomics, Smithsonian's National Zoo and Conservation Biology Institute, Washington, District of Columbia, USA.,Department of Nutrition Science, Smithsonian's National Zoo and Conservation Biology Institute, Washington, District of Columbia, USA
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26
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Aburahma A, Stewart EL, Rana S, Larsen R, Ward CS, Sprague JE. Influence of fecal microbial transplant (FMT) between male and female rats on methamphetamine-induced hyperthermia. Int J Hyperthermia 2023; 40:2159072. [PMID: 36581324 DOI: 10.1080/02656736.2022.2159072] [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: 12/31/2022] Open
Abstract
OBJECTIVE To investigate the effect of bidirectional fecal microbial transplant (FMT) between male and female rats on methamphetamine (MA)-induced hyperthermia. METHODS FMT was performed between male and female rats prior to MA (10 mg/kg, sc) treatment. Core body temperature, plasma drug and norepinephrine (NE) levels were measured and compared between treatment groups. 16S rRNA gene sequencing of bacterial communities between male and female rats was performed. RESULTS MA treatment resulted in significantly higher core body temperatures in male groups (control and FMT-treated) compared to MA-treated female groups (control and FMT-treated). Plasma concentrations of MA and amphetamine were higher in females than males. Whereas, plasma norepinephrine (NE) levels were not different between male and female rats 90 minutes after MA treatment. At the phyla level, the microbiome of male and female control rats were dominated by Firmicutes and Bacteroidetes. Males had a higher relative abundance of Firmicutes and lower relative abundances of Bacteroidetes than females. The FMT procedure changed the recipient group towards their donor with males getting closer to their donors than females. In the control groups following MA treatment, Firmicutes increased and Bacteroides decreased in females and males. Conversely, in the FMT treatment groups following MA treatment, Firmicutes decreased while Bacteroidetes increased in females and males. CONCLUSIONS Although definite differences in the structure and diversity of the gut microbiome were observed using 16S rRNA gene sequencing of bacterial communities between male and female rats, these differences do not seem to contribute to the sex-based differences in MA-induced hyperthermia.
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Affiliation(s)
- Amal Aburahma
- The Ohio Attorney General's Center for the Future of Forensic Science, Bowling Green State University, Bowling Green, OH, USA
| | - Emma L Stewart
- The Ohio Attorney General's Center for the Future of Forensic Science, Bowling Green State University, Bowling Green, OH, USA
| | - Srishti Rana
- The Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, USA
| | - Ray Larsen
- The Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, USA
| | - Christopher S Ward
- The Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, USA
| | - Jon E Sprague
- The Ohio Attorney General's Center for the Future of Forensic Science, Bowling Green State University, Bowling Green, OH, USA
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27
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Gut microbiota modulates lung fibrosis severity following acute lung injury in mice. Commun Biol 2022; 5:1401. [PMID: 36543914 PMCID: PMC9772329 DOI: 10.1038/s42003-022-04357-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 12/09/2022] [Indexed: 12/24/2022] Open
Abstract
Independent studies demonstrate the significance of gut microbiota on the pathogenesis of chronic lung diseases; yet little is known regarding the role of the gut microbiota in lung fibrosis progression. Here we show, using the bleomycin murine model to quantify lung fibrosis in C57BL/6 J mice housed in germ-free, animal biosafety level 1 (ABSL-1), or animal biosafety level 2 (ABSL-2) environments, that germ-free mice are protected from lung fibrosis, while ABSL-1 and ABSL-2 mice develop mild and severe lung fibrosis, respectively. Metagenomic analysis reveals no notable distinctions between ABSL-1 and ABSL-2 lung microbiota, whereas greater microbial diversity, with increased Bifidobacterium and Lactobacilli, is present in ABSL-1 compared to ABSL-2 gut microbiota. Flow cytometric analysis reveals enhanced IL-6/STAT3/IL-17A signaling in pulmonary CD4 + T cells of ABSL-2 mice. Fecal transplantation of ABSL-2 stool into germ-free mice recapitulated more severe fibrosis than transplantation of ABSL-1 stool. Lactobacilli supernatant reduces collagen 1 A production in IL-17A- and TGFβ1-stimulated human lung fibroblasts. These findings support a functional role of the gut microbiota in augmenting lung fibrosis severity.
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28
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Li K, Yang J, Zhou X, Wang H, Ren Y, Huang Y, Liu H, Zhong Z, Peng G, Zheng C, Zhou Z. The Mechanism of Important Components in Canine Fecal Microbiota Transplantation. Vet Sci 2022; 9:vetsci9120695. [PMID: 36548856 PMCID: PMC9786814 DOI: 10.3390/vetsci9120695] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is a potential treatment for many intestinal diseases. In dogs, FMT has been shown to have positive regulation effects in treating Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), canine parvovirus (CPV) enteritis, acute diarrhea (AD), and acute hemorrhagic diarrhea syndrome (AHDS). FMT involves transplanting the functional components of a donor's feces into the gastrointestinal tract of the recipient. The effective components of FMT not only include commensal bacteria, but also include viruses, fungi, bacterial metabolites, and immunoglobulin A (IgA) from the donor feces. By affecting microbiota and regulating host immunity, these components can help the recipient to restore their microbial community, improve their intestinal barrier, and induce anti-inflammation in their intestines, thereby affecting the development of diseases. In addition to the above components, mucin proteins and intestinal epithelial cells (IECs) may be functional ingredients in FMT as well. In addition to the abovementioned indications, FMT is also thought to be useful in treating some other diseases in dogs. Consequently, when preparing FMT fecal material, it is important to preserve the functional components involved. Meanwhile, appropriate fecal material delivery methods should be chosen according to the mechanisms these components act by in FMT.
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Affiliation(s)
- Kerong Li
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
- Chengdu Center for Animal Disease Prevention and Control, Chengdu 610041, China
| | - Jie Yang
- Sichuan Institute of Musk Deer Breeding, Chengdu 610016, China
| | - Xiaoxiao Zhou
- Chengdu Center for Animal Disease Prevention and Control, Chengdu 610041, China
| | - Huan Wang
- Sichuan Institute of Musk Deer Breeding, Chengdu 610016, China
| | - Yuxin Ren
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
- Chengdu Center for Animal Disease Prevention and Control, Chengdu 610041, China
| | - Yunchuan Huang
- Chengdu Center for Animal Disease Prevention and Control, Chengdu 610041, China
| | - Haifeng Liu
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Zhijun Zhong
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Guangneng Peng
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Chengli Zheng
- Sichuan Institute of Musk Deer Breeding, Chengdu 610016, China
- Correspondence: (C.Z.); (Z.Z.)
| | - Ziyao Zhou
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
- Correspondence: (C.Z.); (Z.Z.)
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29
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Najafi-Ghalehlou N, Feizkhah A, Mobayen M, Pourmohammadi-Bejarpasi Z, Shekarchi S, Roushandeh AM, Roudkenar MH. Plumping up a Cushion of Human Biowaste in Regenerative Medicine: Novel Insights into a State-of-the-Art Reserve Arsenal. Stem Cell Rev Rep 2022; 18:2709-2739. [PMID: 35505177 PMCID: PMC9064122 DOI: 10.1007/s12015-022-10383-3] [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] [Accepted: 04/25/2022] [Indexed: 12/03/2022]
Abstract
Major breakthroughs and disruptive methods in disease treatment today owe their thanks to our inch by inch developing conception of the infinitive aspects of medicine since the very beginning, among which, the role of the regenerative medicine can on no account be denied, a branch of medicine dedicated to either repairing or replacing the injured or diseased cells, organs, and tissues. A novel means to accomplish such a quest is what is being called "medical biowaste", a large assortment of biological samples produced during a surgery session or as a result of physiological conditions and biological activities. The current paper accentuating several of a number of promising sources of biowaste together with their plausible applications in routine clinical practices and the confronting challenges aims at inspiring research on the existing gap between clinical and basic science to further extend our knowledge and understanding concerning the potential applications of medical biowaste.
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Affiliation(s)
- Nima Najafi-Ghalehlou
- Department of Medical Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Feizkhah
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammadreza Mobayen
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Zahra Pourmohammadi-Bejarpasi
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Shima Shekarchi
- Anatomical Sciences Department, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mehryar Habibi Roudkenar
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
- Cardiovascular Diseases Research Center, Department of Cardiology, School of Medicine, Heshmat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
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30
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Li Y, Li X, Wu Y, Zhang W. Effects of fecal microbiota transplantation from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein calves. Front Microbiol 2022; 13:898505. [PMID: 36212876 PMCID: PMC9537452 DOI: 10.3389/fmicb.2022.898505] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/02/2022] [Indexed: 11/13/2022] Open
Abstract
This study was conducted to investigate the effect of fecal microbiota transplantation (FMT) from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein Calves. In this study, 50 calves were randomly divided into five groups of 10 each: NC group (no supplementation), Control group (normal saline), low concentration FMT group (LFMT, 1 × 108 CFU/ml), high concentration FMT group (HMFT, 1 × 109 CFU/ml), and sterilized FMT group (SMFT, sterilized bacterial solution). The test lasted for 30 days. We found that FMT reduced the incidence of diarrhea in weaned calves, and the anti-diarrhea effect of LFMT was stronger than those of HFMT and SFMT. Calf feces were collected by rectal palpation on days 5, 10, 15, and 20 post-weaning, and high-throughput sequencing of bacterial 16S rRNA and fungal internal transcribed spacer region of fecal microbiota was performed. We observed that the richness and diversity of bacterial microbiota in the LFMT, HFMT, and SFMT groups were higher than those in the NC and Control groups at day 20 after weaning. The treatment had a significant effect on bacterial richness (p < 0.05), but not on fungal diversity or richness. The analysis of gut microbiome showed that Firmicutes and Bacteroides were the main bacterial phyla in the feces of weaned calves, and norank_ f Muribaculaceae, UCG-005, Rikenellaceae_RC9_gut_group, Bacteroides, and Blautia were the main genera. Ascomycota and Basidiomycota were the main fungal phyla. Compared to abundance parameters in the Control and NC groups, relative abundances of Firmicutes in the FMT groups increased at different time points after weaning. The relative abundance of Blautia and Lactobacillus in the LFMT group increased significantly after weaning. In addition, abundances of Ruminococcus and Romboutsia, which produce short-chain fatty acids, were also increased in different FMT groups. FMT significantly increased the relative abundance of beneficial bacteria, enhanced the complexity of the fecal microbial network, and promoted important metabolic and cellular processes in weaned calves. In conclusion, our study provides a reference and theoretical basis for FMT to prevent calf weaning diarrhea and other intestinal diseases in ruminants.
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Affiliation(s)
- Yuanyuan Li
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Xin Li
- College of Life Sciences, Shihezi University, Shihezi, China
| | - Yanyan Wu
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Wenju Zhang
- College of Animal Science and Technology, Shihezi University, Shihezi, China
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31
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Drivers and determinants of strain dynamics following fecal microbiota transplantation. Nat Med 2022; 28:1902-1912. [PMID: 36109636 PMCID: PMC9499871 DOI: 10.1038/s41591-022-01913-0] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 06/23/2022] [Indexed: 02/06/2023]
Abstract
AbstractFecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor–recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.
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32
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Zaytsoff SJM, Montina T, Boras VF, Brassard J, Moote PE, Uwiera RRE, Inglis GD. Microbiota Transplantation in Day-Old Broiler Chickens Ameliorates Necrotic Enteritis via Modulation of the Intestinal Microbiota and Host Immune Responses. Pathogens 2022; 11:pathogens11090972. [PMID: 36145404 PMCID: PMC9503007 DOI: 10.3390/pathogens11090972] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/22/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
A microbiota transplant (MT) originating from mature adult chicken ceca and propagated in bioreactors was administered to day-old broiler chicks to ascertain the degree to which, and how, the MT affects Clostridium perfringens (Cp)-incited necrotic enteritis (NE). Using a stress predisposition model of NE, birds administered the MT and challenged with Cp showed fewer necrotic lesions, and exhibited a substantially higher α- and β-diversity of bacteria in their jejunum and ceca. Birds challenged with Cp and not administered the MT showed decreased Lactobacillus and increased Clostridium sensu strico 1 in the jejunum. In ceca, Megamonas, a genus containing butyrate-producing bacteria, was only present in birds administered the MT, and densities of this genus were increased in birds challenged with Cp. Metabolite profiles in cecal digesta were altered in birds administered the MT and challenged with the pathogen; 59 metabolites were differentially abundant following MT treatment, and the relative levels of short chain fatty acids, butyrate, valerate, and propionate, were decreased in birds with NE. Birds administered the MT and challenged with Cp showed evidence of enhanced restoration of intestinal barrier functions, including elevated mRNA of MUC2B, MUC13, and TJP1. Likewise, birds administered the MT exhibited higher mRNA of IL2, IL17A, and IL22 at 2-days post-inoculation with Cp, indicating that these birds were better immunologically equipped to respond to pathogen challenge. Collectively, study findings demonstrated that administering a MT containing a diverse mixture of microorganisms to day-old birds ameliorated NE in broilers by increasing bacterial diversity and promoting positive immune responses.
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Affiliation(s)
- Sarah J. M. Zaytsoff
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Tony Montina
- Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada
| | - Valerie F. Boras
- Chinook Regional Hospital, Alberta Health Services, Lethbridge, AB T1J 1W5, Canada
| | - Julie Brassard
- Saint-Hyacinthe Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, QC J2S 8E3, Canada
| | - Paul E. Moote
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
| | - Richard R. E. Uwiera
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - G. Douglas Inglis
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
- Correspondence:
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Sindhunata DP, Meijnikman AS, Gerdes VE, Nieuwdorp M. Dietary fructose as a metabolic risk factor. Am J Physiol Cell Physiol 2022; 323:C847-C856. [DOI: 10.1152/ajpcell.00439.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Over the last decades, the role of the intestinal microbiota in metabolic diseases has come forward. In this regard, both composition and function of our intestinal microbiota is highly variable and influenced by multiple factors, of which diet is one of the major elements. Between 1970 and 1990 diet composition has changed and consumption of dietary sugars has increased, of which fructose intake rose by more than tenfold. This increased intake of sugars and fructose is considered as one of the major risk factors in the developments of obesity and several metabolic disturbances. In this review, we describe the association of dietary fructose intake with insulin resistance, non-alcoholic fatty liver disease (NAFLD) and lipid metabolism. Moreover, we will focus on the potential causality of this altered gut microbiota using fecal transplantation studies in human metabolic disease and whether fecal microbial transplant can reverse this phenotype.
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Affiliation(s)
- Daniko P. Sindhunata
- Department of Experimental Vascular Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands
- Department of Internal Medicine, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM, Hoofddorp, the Netherlands
- Department of Vascular Medicine, Amsterdam University Medical Center Amsterdam, the Netherlands
| | - Abraham Stijn Meijnikman
- Department of Experimental Vascular Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands
- Department of Vascular Medicine, Amsterdam University Medical Center Amsterdam, the Netherlands
| | - Victor E.A. Gerdes
- Department of Internal Medicine, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM, Hoofddorp, the Netherlands
- Department of Vascular Medicine, Amsterdam University Medical Center Amsterdam, the Netherlands
| | - Max Nieuwdorp
- Department of Experimental Vascular Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands
- Department of Vascular Medicine, Amsterdam University Medical Center Amsterdam, the Netherlands
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Dwaib HS, AlZaim I, Ajouz G, Eid AH, El-Yazbi A. Sex Differences in Cardiovascular Impact of Early Metabolic Impairment: Interplay between Dysbiosis and Adipose Inflammation. Mol Pharmacol 2022; 102:481-500. [PMID: 34732528 DOI: 10.1124/molpharm.121.000338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 10/23/2021] [Indexed: 11/22/2022] Open
Abstract
The evolving view of gut microbiota has shifted toward describing the colonic flora as a dynamic organ in continuous interaction with systemic physiologic processes. Alterations of the normal gut bacterial profile, known as dysbiosis, has been linked to a wide array of pathologies. Of particular interest is the cardiovascular-metabolic disease continuum originating from positive energy intake and high-fat diets. Accumulating evidence suggests a role for sex hormones in modulating the gut microbiome community. Such a role provides an additional layer of modulation of the early inflammatory changes culminating in negative metabolic and cardiovascular outcomes. In this review, we will shed the light on the role of sex hormones in cardiovascular dysfunction mediated by high-fat diet-induced dysbiosis, together with the possible involvement of insulin resistance and adipose tissue inflammation. Insights into novel therapeutic interventions will be discussed as well. SIGNIFICANCE STATEMENT: Increasing evidence implicates a role for dysbiosis in the cardiovascular complications of metabolic dysfunction. This minireview summarizes the available data on the sex-based differences in gut microbiota alterations associated with dietary patterns leading to metabolic impairment. A role for a differential impact of adipose tissue inflammation across sexes in mediating the cardiovascular detrimental phenotype following diet-induced dysbiosis is proposed. Better understanding of this pathway will help introduce early approaches to mitigate cardiovascular deterioration in metabolic disease.
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Affiliation(s)
- Haneen S Dwaib
- Department of Pharmacology and Toxicology, Faculty of Medicine (H.S.D., I.A., G.A., A.E.-Y.), Department of Nutrition and Food Sciences, Faculty of Agricultural and Food Sciences (H.S.D.), American University of Beirut, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon (I.A.); Department of Basic Medical Sciences, College of Medicine (A.H.E.), Biomedical and Pharmaceutical Research Unit, QU Health (A.H.E.), Qatar University, Doha, Qatar; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt (A.E.-Y.); and Faculty of Pharmacy, Alalamein International University, Alalamein, Egypt (A.E.-Y.)
| | - Ibrahim AlZaim
- Department of Pharmacology and Toxicology, Faculty of Medicine (H.S.D., I.A., G.A., A.E.-Y.), Department of Nutrition and Food Sciences, Faculty of Agricultural and Food Sciences (H.S.D.), American University of Beirut, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon (I.A.); Department of Basic Medical Sciences, College of Medicine (A.H.E.), Biomedical and Pharmaceutical Research Unit, QU Health (A.H.E.), Qatar University, Doha, Qatar; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt (A.E.-Y.); and Faculty of Pharmacy, Alalamein International University, Alalamein, Egypt (A.E.-Y.)
| | - Ghina Ajouz
- Department of Pharmacology and Toxicology, Faculty of Medicine (H.S.D., I.A., G.A., A.E.-Y.), Department of Nutrition and Food Sciences, Faculty of Agricultural and Food Sciences (H.S.D.), American University of Beirut, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon (I.A.); Department of Basic Medical Sciences, College of Medicine (A.H.E.), Biomedical and Pharmaceutical Research Unit, QU Health (A.H.E.), Qatar University, Doha, Qatar; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt (A.E.-Y.); and Faculty of Pharmacy, Alalamein International University, Alalamein, Egypt (A.E.-Y.)
| | - Ali H Eid
- Department of Pharmacology and Toxicology, Faculty of Medicine (H.S.D., I.A., G.A., A.E.-Y.), Department of Nutrition and Food Sciences, Faculty of Agricultural and Food Sciences (H.S.D.), American University of Beirut, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon (I.A.); Department of Basic Medical Sciences, College of Medicine (A.H.E.), Biomedical and Pharmaceutical Research Unit, QU Health (A.H.E.), Qatar University, Doha, Qatar; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt (A.E.-Y.); and Faculty of Pharmacy, Alalamein International University, Alalamein, Egypt (A.E.-Y.)
| | - Ahmed El-Yazbi
- Department of Pharmacology and Toxicology, Faculty of Medicine (H.S.D., I.A., G.A., A.E.-Y.), Department of Nutrition and Food Sciences, Faculty of Agricultural and Food Sciences (H.S.D.), American University of Beirut, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon (I.A.); Department of Basic Medical Sciences, College of Medicine (A.H.E.), Biomedical and Pharmaceutical Research Unit, QU Health (A.H.E.), Qatar University, Doha, Qatar; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt (A.E.-Y.); and Faculty of Pharmacy, Alalamein International University, Alalamein, Egypt (A.E.-Y.)
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Huang WQ, Huang HL, Peng W, Liu YD, Zhou YL, Xu HM, Zhang LJ, Zhao C, Nie YQ. Altered Pattern of Immunoglobulin A-Targeted Microbiota in Inflammatory Bowel Disease After Fecal Transplantation. Front Microbiol 2022; 13:873018. [PMID: 35814647 PMCID: PMC9257281 DOI: 10.3389/fmicb.2022.873018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 05/09/2022] [Indexed: 12/02/2022] Open
Abstract
Adaptive immune response to the gut microbiota is one of the main drivers of inflammatory bowel disease (IBD). Under inflammatory conditions, immunoglobulin (Ig)-targeted bacteria are altered. However, changes in Ig-targeted bacteria in Asian patients with IBD with ulcerative colitis (UC) remain unclear. Furthermore, changes in IgA-targeted bacteria in patients with UC treated with fecal microbiota transplantation (FMT) are unclear. Here, we analyzed fecal samples of patients with IBD and patients with UC before and after FMT by flow cytometry. We found that the percentage of IgA/G-coated bacteria can be used to assess the severity of IBD. Besides oral pharyngeal bacteria such as Streptococcus, we hypothesized that Megamonas, Acinetobacter, and, especially, Staphylococcus might play an important role in IBD pathogenesis. Moreover, we evaluated the influence of FMT on IgA-coated bacteria in patients with UC. We found that IgA-bacterial interactions were re-established in human FMT recipients and resembled those in the healthy fecal donors. Additionally, the IgA targeting was not influenced by delivery methods: gastroscopy spraying and colonic transendoscopic enteral tubing (TET). Then, we established an acute dextran sulfate sodium (DSS)-induced mouse model to explore whether FMT intervention would impact IgA/G memory B cell in the intestine. We found that after FMT, both IgA/G memory B cell and the percentage of IgA/G-targeted bacteria were restored to normal levels in DSS mice.
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Affiliation(s)
- Wen-qi Huang
- Department of Gastroenterology, School of Medicine, The Second Affiliated Hospital, South China University of Technology, Guangzhou, China
| | - Hong-Li Huang
- Department of Gastroenterology, School of Medicine, The Second Affiliated Hospital, South China University of Technology, Guangzhou, China
| | - Wu Peng
- Department of Gastroenterology, School of Medicine, The Second Affiliated Hospital, South China University of Technology, Guangzhou, China
| | - Yan-Di Liu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou, China
| | - You-Lian Zhou
- Department of Gastroenterology, School of Medicine, The Second Affiliated Hospital, South China University of Technology, Guangzhou, China
| | - Hao-Ming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou, China
| | - Liang-jie Zhang
- Department of Infectious Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Chong Zhao
- Department of Gastroenterology, School of Medicine, The Second Affiliated Hospital, South China University of Technology, Guangzhou, China
| | - Yu-Qiang Nie
- Department of Gastroenterology, School of Medicine, The Second Affiliated Hospital, South China University of Technology, Guangzhou, China
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Krela-Kaźmierczak I, Zakerska-Banaszak O, Skrzypczak-Zielińska M, Łykowska-Szuber L, Szymczak-Tomczak A, Zawada A, Rychter AM, Ratajczak AE, Skoracka K, Skrzypczak D, Marcinkowska E, Słomski R, Dobrowolska A. Where Do We Stand in the Behavioral Pathogenesis of Inflammatory Bowel Disease? The Western Dietary Pattern and Microbiota-A Narrative Review. Nutrients 2022; 14:nu14122520. [PMID: 35745251 PMCID: PMC9230670 DOI: 10.3390/nu14122520] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 02/06/2023] Open
Abstract
Despite the increasing knowledge with regard to IBD (inflammatory bowel disease), including ulcerative colitis (UC) and Crohn’s disease (CD), the etiology of these conditions is still not fully understood. Apart from immunological, environmental and nutritional factors, which have already been well documented, it is worthwhile to look at the possible impact of genetic factors, as well as the composition of the microbiota in patients suffering from IBD. New technologies in biochemistry allow to obtain information that can add to the current state of knowledge in IBD etiology.
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Affiliation(s)
- Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | - Oliwia Zakerska-Banaszak
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań, Poland; (M.S.-Z.); (R.S.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | | | - Liliana Łykowska-Szuber
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Alicja Ewa Ratajczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Kinga Skoracka
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Dorota Skrzypczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | - Emilia Marcinkowska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Ryszard Słomski
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań, Poland; (M.S.-Z.); (R.S.)
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
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Alberdi A, Andersen SB, Limborg MT, Dunn RR, Gilbert MTP. Disentangling host-microbiota complexity through hologenomics. Nat Rev Genet 2022; 23:281-297. [PMID: 34675394 DOI: 10.1038/s41576-021-00421-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2021] [Indexed: 02/07/2023]
Abstract
Research on animal-microbiota interactions has become a central topic in biological sciences because of its relevance to basic eco-evolutionary processes and applied questions in agriculture and health. However, animal hosts and their associated microbial communities are still seldom studied in a systemic fashion. Hologenomics, the integrated study of the genetic features of a eukaryotic host alongside that of its associated microbes, is becoming a feasible - yet still underexploited - approach that overcomes this limitation. Acknowledging the biological and genetic properties of both hosts and microbes, along with the advantages and disadvantages of implemented techniques, is essential for designing optimal studies that enable some of the major questions in biology to be addressed.
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Affiliation(s)
- Antton Alberdi
- Center for Evolutionary Hologenomics, The GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.
| | - Sandra B Andersen
- Center for Evolutionary Hologenomics, The GLOBE Institute, University of Copenhagen, Copenhagen, Denmark
| | - Morten T Limborg
- Center for Evolutionary Hologenomics, The GLOBE Institute, University of Copenhagen, Copenhagen, Denmark
| | - Robert R Dunn
- Center for Evolutionary Hologenomics, The GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.,Department of Applied Ecology, North Carolina State University, Raleigh, NC, USA
| | - M Thomas P Gilbert
- Center for Evolutionary Hologenomics, The GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.,University Museum, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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38
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Isidori M, Corbee RJ, Trabalza-Marinucci M. Nonpharmacological Treatment Strategies for the Management of Canine Chronic Inflammatory Enteropathy—A Narrative Review. Vet Sci 2022; 9:vetsci9020037. [PMID: 35202290 PMCID: PMC8878421 DOI: 10.3390/vetsci9020037] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/15/2022] [Accepted: 01/17/2022] [Indexed: 02/04/2023] Open
Abstract
Chronic inflammatory enteropathy (CIE) refers to a heterogeneous group of idiopathic diseases of the dog characterised by persistent gastrointestinal (GI) clinical signs. If conventional dietary treatment alone would be unsuccessful, management of CIE is traditionally attained by the use of pharmaceuticals, such as antibiotics and immunosuppressive drugs. While being rather effective, however, these drugs are endowed with side effects, which may impact negatively on the animal’s quality of life. Therefore, novel, safe and effective therapies for CIE are highly sought after. As gut microbiota imbalances are often associated with GI disorders, a compelling rationale exists for the use of nonpharmacological methods of microbial manipulation in CIE, such as faecal microbiota transplantation and administration of pre-, pro-, syn- and postbiotics. In addition to providing direct health benefits to the host via a gentle modulation of the intestinal microbiota composition and function, these treatments may also possess immunomodulatory and epithelial barrier-enhancing actions. Likewise, intestinal barrier integrity, along with mucosal inflammation, are deemed to be two chief therapeutic targets of mesenchymal stem cells and selected vegetable-derived bioactive compounds. Although pioneering studies have revealed encouraging findings regarding the use of novel treatment agents in CIE, a larger body of research is needed to address fully their mode of action, efficacy and safety.
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Affiliation(s)
- Marco Isidori
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy;
- Correspondence:
| | - Ronald Jan Corbee
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM Utrecht, The Netherlands;
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Manrique P, Zhu Y, van der Oost J, Herrema H, Nieuwdorp M, de Vos WM, Young M. Gut bacteriophage dynamics during fecal microbial transplantation in subjects with metabolic syndrome. Gut Microbes 2022; 13:1-15. [PMID: 33794724 PMCID: PMC8023239 DOI: 10.1080/19490976.2021.1897217] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Metabolic Syndrome (MetS) is a growing public health concern worldwide. Individuals with MetS have an increased risk for cardiovascular (CV) disease and type 2 diabetes (T2D). These diseases - in part preventable with the treatment of MetS - increase the chances of premature death and pose a great economic burden to health systems. A healthy gut microbiota is associated with a reduction in MetS, T2D, and CV disease. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict. Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects. We performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant, n = 3) or a treatment group (healthy-donor-stool transplant; n-recipients = 6, n-donors = 5). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced. We found that FMT from healthy donors significantly alters the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, we identified bacteriophage groups that could explain these differences and we examined their prevalence in individuals from a larger cohort of MetS FMT trial.Trial information- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2705; NTR 2705.
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Affiliation(s)
- Pilar Manrique
- Department of Microbiology & Immunology, Montana State University, Bozeman, MT, USA
| | - Yifan Zhu
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - John van der Oost
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Hilde Herrema
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, AZ Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, AZ Amsterdam, The Netherlands
| | - Willem M. de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands,RPU Human Microbiology, University of Helsinki, Faculty of Medicine, Helsinki, Finland
| | - Mark Young
- Department of Plant Sciences & Plant Pathology, Montana State University, Bozeman, MT, USA,CONTACT Mark Young Department of Plant Sciences & Plant Pathology, Montana State University, P.O. Box 173150, Bozeman, MT59717-3150, USA
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40
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El-Sahhar S, Varga-Weisz P. The gut microbiome in health and disease: Inflammatory bowel diseases. ADV ECOL RES 2022. [DOI: 10.1016/bs.aecr.2022.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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41
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Tan P, Liu H, Zhao J, Gu X, Wei X, Zhang X, Ma N, Johnston LJ, Bai Y, Zhang W, Nie C, Ma X. Amino acids metabolism by rumen microorganisms: Nutrition and ecology strategies to reduce nitrogen emissions from the inside to the outside. THE SCIENCE OF THE TOTAL ENVIRONMENT 2021; 800:149596. [PMID: 34426337 DOI: 10.1016/j.scitotenv.2021.149596] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/06/2021] [Accepted: 08/07/2021] [Indexed: 06/13/2023]
Abstract
For the ruminant animal industry, the emission of nitrogenous substances, such as nitrous oxide (N2O) and ammonia (NH3), not only challenges environmental sustainability but also restricts its development. The metabolism of proteins and amino acids by rumen microorganisms is a key factor affecting nitrogen (N) excretion in ruminant animals. Rumen microorganisms that affect N excretion mainly include three types: proteolytic and peptidolytic bacteria (PPB), ureolytic bacteria (UB), and hyper-ammonia-producing bacteria (HAB). Microbes residing in the rumen, however, are influenced by several complex factors, such as diet, which results in fluctuations in the rumen metabolism of proteins and amino acids and ultimately affects N emission. Combining feed nutrition strategies (including ingredient adjustment and feed additives) and ecological mitigation strategies of N2O and NH3 in industrial practice can reduce the emission of nitrogenous pollutants from the ruminant breeding industry. In this review, the characteristics of the rumen microbial community related to N metabolism in ruminants were used as the metabolic basis. Furthermore, an effective strategy to increase N utilisation efficiency in combination with nutrition and ecology was reviewed to provide an inside-out approach to reduce N emissions from ruminants.
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Affiliation(s)
- Peng Tan
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Han Liu
- College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Jing Zhao
- College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Xueling Gu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Xiaobing Wei
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Xiaojian Zhang
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Ning Ma
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Lee J Johnston
- West Central Research & Outreach Center, University of Minnesota, Morris, MN 56267, USA
| | - Yueyu Bai
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Wenju Zhang
- College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Cunxi Nie
- College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Xi Ma
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China.
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How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection. Clin Microbiol Infect 2021; 28:502-512. [PMID: 34826617 DOI: 10.1016/j.cmi.2021.11.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 10/06/2021] [Accepted: 11/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Vulnerable patients with intestinal colonization of multidrug-resistant organisms (MDROs) are recognized to be at increased risk of invasive MDRO-driven infection. Intestinal microbiota transplantation (IMT, also called faecal microbiota transplant) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection. OBJECTIVES To describe how to establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimizing administration and assessment of endpoints. SOURCES Expert guidelines and peer-reviewed clinical studies are encompassed and discussed. CONTENT IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) and take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT is timed for when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least 2 weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonization as a binary outcome. Repeat IMT is considered case by case. IMPLICATIONS Future research areas should include randomized studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional microbiome components that could be used therapeutically.
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Bokoliya SC, Dorsett Y, Panier H, Zhou Y. Procedures for Fecal Microbiota Transplantation in Murine Microbiome Studies. Front Cell Infect Microbiol 2021; 11:711055. [PMID: 34621688 PMCID: PMC8490673 DOI: 10.3389/fcimb.2021.711055] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 08/24/2021] [Indexed: 12/11/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has been widely recognized as an approach to determine the microbiome’s causal role in gut dysbiosis-related disease models and as a novel disease-modifying therapy. Despite potential beneficial FMT results in various disease models, there is a variation and complexity in procedural agreement among research groups for performing FMT. The viability of the microbiome in feces and its successful transfer depends on various aspects of donors, recipients, and lab settings. This review focuses on the technical practices of FMT in animal studies. We first document crucial factors required for collecting, handling, and processing donor fecal microbiota for FMT. Then, we detail the description of gut microbiota depletion methods, FMT dosages, and routes of FMT administrations in recipients. In the end, we describe assessments of success rates of FMT with sustainability. It is critical to work under the anaerobic condition to preserve as much of the viability of bacteria. Utilization of germ- free mice or depletion of recipient gut microbiota by antibiotics or polyethylene glycol are two common recipient preparation approaches to achieve better engraftment. Oral-gastric gavage preferred by most researchers for fast and effective administration of FMT in mice. Overall, this review highlights various methods that may lead to developing the standard and reproducible protocol for FMT.
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Affiliation(s)
- Suresh C Bokoliya
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
| | - Yair Dorsett
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
| | - Hunter Panier
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
| | - Yanjiao Zhou
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
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Yang M, Gu Y, Li L, Liu T, Song X, Sun Y, Cao X, Wang B, Jiang K, Cao H. Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside. Nutrients 2021; 13:nu13093143. [PMID: 34579027 PMCID: PMC8467364 DOI: 10.3390/nu13093143] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid–gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.
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Affiliation(s)
- Min Yang
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Yu Gu
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Lingfeng Li
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Xueli Song
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Yue Sun
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Xiaocang Cao
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
| | - Kui Jiang
- Graduate School of Tianjin Medical University, Tianjin 300070, China
- Correspondence: (K.J.); (H.C.)
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; (M.Y.); (Y.G.); (L.L.); (T.L.); (X.S.); (Y.S.); (X.C.); (B.W.)
- Correspondence: (K.J.); (H.C.)
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Paley EL. Towards Understanding COVID-19: Molecular Insights, Co-infections, Associated Disorders, and Aging. J Alzheimers Dis Rep 2021; 5:571-600. [PMID: 34514341 PMCID: PMC8385430 DOI: 10.3233/adr-210010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND COVID-19 can be related to any diseases caused by microbial infection(s) because 1) co-infection with COVID-19-related virus and other microorganism(s) and 2) because metabolites produced by microorganisms such as bacteria, fungi, and protozoan can be involved in necrotizing pneumonia and other necrotizing medical conditions observed in COVID-19. OBJECTIVE By way of illustration, the microbial metabolite of aromatic amino acid tryptophan, a biogenic amine tryptamine inducing neurodegeneration in cell and animal models, also induces necrosis. METHODS This report includes analysis of COVID-19 positivity by zip codes in Florida and relation of the positivity to population density, possible effect of ecological and social factors on spread of COVID-19, autopsy analysis of COVID-19 cases from around the world, serum metabolomics analysis, and evaluation of autoantigenome related to COVID-19. RESULTS In the present estimations, COVID-19 positivity percent per zip code population varied in Florida from 4.65% to 44.3% (February 2021 data). COVID-19 analysis is partially included in my book Microbial Metabolism and Disease (2021). The autoantigenome related to COVID-19 is characterized by alterations in protein biosynthesis proteins including aminoacyl-tRNA synthetases. Protein biosynthesis alteration is a feature of Alzheimer's disease. Serum metabolomics of COVID-19 positive patients show alteration in shikimate pathway metabolism, which is associated with the presence of Alzheimer's disease-associated human gut bacteria. CONCLUSION Such alterations in microbial metabolism and protein biosynthesis can lead to toxicity and neurodegeneration as described earlier in my book Protein Biosynthesis Interference in Disease (2020).
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Affiliation(s)
- Elena L. Paley
- Expert BioMed, Inc. and Nonprofit Public Charity Stop Alzheimers Corp., Miami-Dade, FL, USA
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46
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Zalomova LV, Reshetnikov DA, Ugraitskaya SV, Mezhevikina LM, Zagainova AV, Makarov VV, Yudin SM, Fesenko EE. Fetal Serum in Combination with 5% Dimethyl Sulfoxide Efficiently Protects the Human Gut Microbiota during Cryopreservation in Liquid Nitrogen. Biophysics (Nagoya-shi) 2021. [DOI: 10.1134/s0006350921040230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Fecal microbiota transplantation and antibiotic treatment attenuate naloxone-precipitated opioid withdrawal in morphine-dependent mice. Exp Neurol 2021; 343:113787. [PMID: 34153321 DOI: 10.1016/j.expneurol.2021.113787] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 06/13/2021] [Accepted: 06/16/2021] [Indexed: 12/20/2022]
Abstract
Opioid addiction can produce severe side effects including physical dependence and withdrawal. Perturbations of the gut microbiome have recently been shown to alter opioid-induced side-effects such as addiction, tolerance and dependence. In the present study, we investigated the influence of the gut microbiome on opioid withdrawal by evaluating the effects of fecal microbiota transplantation (FMT), antibiotic and probiotic treatments, and pharmacological inhibition of gut permeability in a mouse model of opioid dependence. Repeated intraperitoneal (i.p.) morphine treatment produced physical dependence that was quantified by measuring somatic signs of withdrawal (i.e. number of jumps) precipitated using the opioid antagonist naloxone. Morphine-dependent mice that received FMT from morphine-treated donor mice exhibited fewer naloxone-precipitated jumps compared to morphine-dependent counterparts receiving FMT from saline-treated donor mice. Microbial contents in the mouse cecum were altered by morphine treatment but were not differentially impacted by FMT. A broad-spectrum antibiotic cocktail (ABX) regimen reduced the bacterial load and attenuated naloxone-precipitated morphine withdrawal in morphine-dependent mice, whereas commercially available probiotic strains did not reliably alter somatic signs of opioid withdrawal. ML-7, a pharmacological inhibitor of gut permeability, reduced the morphine-induced increase in gut permeability in vivo but did not reliably alter somatic signs of naloxone-precipitated opioid withdrawal. Our results suggest that the gut microbiome impacts the development of physical dependence induced by chronic morphine administration, and that therapeutic manipulations of the gut microbiome may reduce opioid withdrawal.
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Battaglini D, Robba C, Fedele A, Trancǎ S, Sukkar SG, Di Pilato V, Bassetti M, Giacobbe DR, Vena A, Patroniti N, Ball L, Brunetti I, Torres Martí A, Rocco PRM, Pelosi P. The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome. Front Med (Lausanne) 2021; 8:671714. [PMID: 34150807 PMCID: PMC8211890 DOI: 10.3389/fmed.2021.671714] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 05/12/2021] [Indexed: 12/12/2022] Open
Abstract
In late December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) quickly spread worldwide, and the syndrome it causes, coronavirus disease 2019 (COVID-19), has reached pandemic proportions. Around 30% of patients with COVID-19 experience severe respiratory distress and are admitted to the intensive care unit for comprehensive critical care. Patients with COVID-19 often present an enhanced immune response with a hyperinflammatory state characterized by a "cytokine storm," which may reflect changes in the microbiota composition. Moreover, the evolution to acute respiratory distress syndrome (ARDS) may increase the severity of COVID-19 and related dysbiosis. During critical illness, the multitude of therapies administered, including antibiotics, sedatives, analgesics, body position, invasive mechanical ventilation, and nutritional support, may enhance the inflammatory response and alter the balance of patients' microbiota. This status of dysbiosis may lead to hyper vulnerability in patients and an inappropriate response to critical circumstances. In this context, the aim of our narrative review is to provide an overview of possible interaction between patients' microbiota dysbiosis and clinical status of severe COVID-19 with ARDS, taking into consideration the characteristic hyperinflammatory state of this condition, respiratory distress, and provide an overview on possible nutritional strategies for critically ill patients with COVID-19-ARDS.
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Affiliation(s)
- Denise Battaglini
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Chiara Robba
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Andrea Fedele
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Sebastian Trancǎ
- Department of Anesthesia and Intensive Care II, Clinical Emergency County Hospital of Cluj, Iuliu Hatieganu, University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Anaesthesia and Intensive Care 1, Clinical Emergency County Hospital Cluj-Napoca, Cluj-Napoca, Romania
| | - Samir Giuseppe Sukkar
- Dietetics and Clinical Nutrition Unit, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Vincenzo Di Pilato
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Matteo Bassetti
- Clinica Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Dipartimento di Scienze della Salute (DISSAL), Università degli Studi di Genova, Genova, Italy
| | - Daniele Roberto Giacobbe
- Clinica Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Dipartimento di Scienze della Salute (DISSAL), Università degli Studi di Genova, Genova, Italy
| | - Antonio Vena
- Clinica Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Nicolò Patroniti
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Lorenzo Ball
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Iole Brunetti
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Antoni Torres Martí
- Department of Medicine, University of Barcelona, Barcelona, Spain
- Division of Animal Experimentation, Department of Pulmonology, Hospital Clinic, Barcelona, Spain
- Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d'investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Patricia Rieken Macedo Rocco
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- COVID-19-Network, Ministry of Science, Technology, Innovation and Communication, Brasilia, Brazil
| | - Paolo Pelosi
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
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Townsend EM, Kelly L, Muscatt G, Box JD, Hargraves N, Lilley D, Jameson E. The Human Gut Phageome: Origins and Roles in the Human Gut Microbiome. Front Cell Infect Microbiol 2021; 11:643214. [PMID: 34150671 PMCID: PMC8213399 DOI: 10.3389/fcimb.2021.643214] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 05/19/2021] [Indexed: 12/14/2022] Open
Abstract
The investigation of the microbial populations of the human body, known as the microbiome, has led to a revolutionary field of science, and understanding of its impacts on human development and health. The majority of microbiome research to date has focussed on bacteria and other kingdoms of life, such as fungi. Trailing behind these is the interrogation of the gut viruses, specifically the phageome. Bacteriophages, viruses that infect bacterial hosts, are known to dictate the dynamics and diversity of bacterial populations in a number of ecosystems. However, the phageome of the human gut, while of apparent importance, remains an area of many unknowns. In this paper we discuss the role of bacteriophages within the human gut microbiome. We examine the methods used to study bacteriophage populations, how this evolved over time and what we now understand about the phageome. We review the phageome development in infancy, and factors that may influence phage populations in adult life. The role and action of the phageome is then discussed at both a biological-level, and in the broader context of human health and disease.
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Affiliation(s)
- Eleanor M Townsend
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Lucy Kelly
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - George Muscatt
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Joshua D Box
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Nicole Hargraves
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Daniel Lilley
- Warwick Medical School, The University of Warwick, Coventry, United Kingdom
| | - Eleanor Jameson
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
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50
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Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future? Cell Metab 2021; 33:1098-1110. [PMID: 34077717 DOI: 10.1016/j.cmet.2021.05.005] [Citation(s) in RCA: 112] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 03/26/2021] [Accepted: 05/05/2021] [Indexed: 12/15/2022]
Abstract
Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.
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