Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition

Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in...

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Autores principales: Ma Liang, Zhang Liwen, Song Jianguo, Dai Juan, Ding Fei, Zhang Yin, Wu Changping, Chen Jianping
Formato: article
Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/be515bd066a14bb2aec3e0ba29beed84
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spelling oai:doaj.org-article:be515bd066a14bb2aec3e0ba29beed842021-12-01T13:36:51ZFecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition1664-322410.3389/fimmu.2021.728723https://doaj.org/article/be515bd066a14bb2aec3e0ba29beed842021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.728723/fullhttps://doaj.org/toc/1664-3224Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5−/−EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.Ma LiangMa LiangZhang LiwenSong JianguoDai JuanDing FeiZhang YinWu ChangpingChen JianpingFrontiers Media S.A.articlefecal microbiota transplantationTFR cellsTFH cellsAIHEAHImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic fecal microbiota transplantation
TFR cells
TFH cells
AIH
EAH
Immunologic diseases. Allergy
RC581-607
spellingShingle fecal microbiota transplantation
TFR cells
TFH cells
AIH
EAH
Immunologic diseases. Allergy
RC581-607
Ma Liang
Ma Liang
Zhang Liwen
Song Jianguo
Dai Juan
Ding Fei
Zhang Yin
Wu Changping
Chen Jianping
Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition
description Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5−/−EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.
format article
author Ma Liang
Ma Liang
Zhang Liwen
Song Jianguo
Dai Juan
Ding Fei
Zhang Yin
Wu Changping
Chen Jianping
author_facet Ma Liang
Ma Liang
Zhang Liwen
Song Jianguo
Dai Juan
Ding Fei
Zhang Yin
Wu Changping
Chen Jianping
author_sort Ma Liang
title Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition
title_short Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition
title_full Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition
title_fullStr Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition
title_full_unstemmed Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition
title_sort fecal microbiota transplantation controls progression of experimental autoimmune hepatitis in mice by modulating the tfr/tfh immune imbalance and intestinal microbiota composition
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/be515bd066a14bb2aec3e0ba29beed84
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