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      Fecal transplantation alleviates acute liver injury in mice through regulating Treg/Th17 cytokines balance

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          Abstract

          Changes in intestinal microecology during acute liver failure (ALF) directly affect the occurrence and development of the disease. The study aimed to investigate the relationship between the intestinal microbiota and the key immune cells. Fecal microbiota transplantation (FMT) was used to determine whether ALF can balance Th17/Treg cytokines. The relationship between gut microbiota and clinical indicators was analyzed. BALB/c mice were treated with d-galactosamine ( d-GalN) to induce a murine ALF model. FMT to d-GalN mice was conducted to test for liver function indicators. Results showed that the proportions of Lachnospiraceae, Prevotella, S24-7, Odoribacter and Rikenellaceae in d-GalN mice with intestinal microbiota disorder were restored after FMT. Further, CIA analysis showed that bacteria had a covariant relationship with clinical indicators. Microbiota could account for changes in 49.9% of the overall clinical indicators. Adonis analysis showed that Ruminococcus, and Enterococcus have a greater impact on clinical indicators. FMT down-regulated the expression of IL-17A, TNF-α, and TGF-β, while up-regulated IL-10 and IL-22. Transplantation of feces from Saccharomyces boulardii donor mice improved GalN-induced liver damage. These findings indicate that FMT attenuates d-GalN-induced liver damage in mice, and a clinical trial is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with ALF.

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          Most cited references42

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          Metagenomic biomarker discovery and explanation

          This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
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            The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

            Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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              Host-gut microbiota metabolic interactions.

              The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
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                Author and article information

                Contributors
                Zhaoxueke1@163.com
                minglianggy@126.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                15 January 2021
                15 January 2021
                2021
                : 11
                : 1611
                Affiliations
                [1 ]GRID grid.413458.f, ISNI 0000 0000 9330 9891, Department of Medical Examination, , Guizhou Medical University, ; Guiyang, Guizhou China
                [2 ]GRID grid.452244.1, Clinical Laboratory Center, , The Affiliated Hospital of Guizhou Medical University, ; Guiyang, Guizhou China
                [3 ]GRID grid.452244.1, Department of Infectious Diseases, , The Affiliated Hospital of Guizhou Medical University, ; No. 28 Guiyang Street, Guiyang, 550002 Guizhou China
                [4 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Department of Clinical Medicine, , Peking University Health Science Center School of Foundational Education, Peking University, ; Beijing, China
                [5 ]Guizhou Maternal and Child Health Care Center, Guiyang, Guizhou China
                [6 ]GRID grid.413458.f, ISNI 0000 0000 9330 9891, Deparment of Blood Transfusion, , The Affiliated Tumor Hospital, Guizhou Medical University, ; Guiyang, Guizhou China
                [7 ]GRID grid.452244.1, Prenatal Diagnosis Center, The Affiliated Hospital of Guizhou Medical University, ; Guiyang, Guizhou China
                [8 ]GRID grid.452244.1, Department of Blood Transfusion, , The Affiliated Hospital of Guizhou Medical University, ; Guiyang, Guizhou China
                [9 ]GRID grid.452244.1, Department of Respiratory, , The Affiliated Hospital of Guizhou Medical University, ; Guiyang, Guizhou China
                Article
                81263
                10.1038/s41598-021-81263-y
                7810881
                33452411
                339d356a-3bac-451a-97cb-2e199a54a5d3
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 May 2020
                : 4 January 2021
                Funding
                Funded by: National Nature Science Foundation of China
                Award ID: 81570543
                Award Recipient :
                Categories
                Article
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                © The Author(s) 2021

                Uncategorized
                microbiology,diseases
                Uncategorized
                microbiology, diseases

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