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

2021 ◽  
Vol 12 ◽  
Author(s):  
Ma Liang ◽  
Zhang Liwen ◽  
Song Jianguo ◽  
Dai Juan ◽  
Ding Fei ◽  
...  

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.

Author(s):  
Phillipp Hartmann ◽  
Bernd Schnabl

AbstractAlcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of both ALD and NAFLD. Here we describe associated changes in the intestinal microbiota, and we detail randomized clinical trials in ALD and NAFLD which evaluate treatments modulating the intestinal microbiome including fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics. Finally, we discuss precision medicine approaches targeting the intestinal microbiome to ameliorate ALD and NAFLD.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sanwang Wang ◽  
Hongliang Chen ◽  
Xin Wen ◽  
Jingjing Mu ◽  
Mingyue Sun ◽  
...  

Objective. To study the protective effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and reveal its potential intestinal microflora-dependent mechanism through analyses of the intestinal microbiota and spinal cord transcriptome in mice. Method. We measured the severity of disease by clinical EAE scores and H&E staining. Gut microbiota alteration in the gut and differentially expressed genes (DEGs) in the spinal cord were analyzed through 16S rRNA and transcriptome sequencing. Finally, we analyzed associations between the relative abundance of intestinal microbiota constituents and DEGs. Results. We observed that clinical EAE scores were lower in the EAE+FMT group than in the EAE group. Meanwhile, mice in the EAE+FMT group also had a lower number of infiltrating cells. The results of 16S rRNA sequence analysis showed that FMT increased the relative abundance of Firmicutes and Proteobacteria and reduced the abundance of Bacteroides and Actinobacteria. Meanwhile, FMT could modulate gut microbiota balance, especially via increasing the relative abundance of g_Adlercreutzia, g_Sutterella, g_Prevotella_9, and g_Tyzzerella_3 and decreasing the relative abundance of g_Turicibacter. Next, we analyzed the transcriptome of mouse spinal cord tissue and found that 1476 genes were differentially expressed between the EAE and FMT groups. The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37. Conclusion. Altogether, FMT may selectively regulate gene expression to improve inflammation and maintain the stability of the intestinal environment in a gut microbiota-dependent manner.


Hepatology ◽  
1985 ◽  
Vol 5 (5) ◽  
pp. 770-777 ◽  
Author(s):  
Teruo Mori ◽  
Yoshio Mori ◽  
Hiromichi Yoshida ◽  
Shiro Ueda ◽  
Makoto Ogawa ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yao Wang ◽  
Fengling Zheng ◽  
Shan Liu ◽  
Huanhuan Luo

Irritable bowel syndrome is a functional disorder characterized by abdominal pain or discomfort associated with altered bowel habits. Due to the uncertainty of the pathogenesis of IBS and the diversity of its clinical manifestations, IBS cannot be completely cured. Increasing evidence suggests the key role of altered intestinal microbiota in the pathogenesis of IBS. Therefore, attention is being shifted to adjusting the changes in intestinal microbiota to control IBS symptoms. Fecal microbiota transplantation (FMT), antibiotics, probiotics, and synbiotics are currently often employed as treatment for IBS. And FMT is the most significant therapeutic efficacy with the least number of side effects. FMT provides a creative way to restore the abnormal gut microbiome in patients with IBS. But although current clinical studies confirm the effectiveness of FMT in the treatment of IBS, they are short-term studies of small samples, and there is still a lack of large-scale long-term studies. In this paper, we review the intestinal microbiota changes of IBS, the common methods of treating IBS with intestinal microbes, and the research status of FMT for the treatment of IBS. Finally, we put forward some opinions on the future research direction of FMT treatment of IBS.


2020 ◽  
Author(s):  
Zhenzhen Yan ◽  
Fan Yang ◽  
Jingwei Cao ◽  
Wencai Ding ◽  
Shi Yan ◽  
...  

Abstract Background: Intestinal microbiota and amino acids that are one of their metabolites play important roles in the mechanism of pathology of Parkinson's disease (PD). It has been reported that the level of amino acids in vivo participate in neurodegeneration by regulating adaptive immune response, while the current researches on alteration of amino acids in intestinal microbiota are still insufficient. Here, we evaluate the correlation between gut microbiota alterations and clinical parameters of PD, amino acid concentrations.Methods: Stool samples from PD and healthy controls were collected for microbiome and targeted metabolome analyses. Results: At the genus level, there was a greater abundance of Rikenellaceae_RC9_gut_group in PD patients with more severe motor symptoms. Metabonomics analysis showed that multiple fecal amino acid concentrations in PD patients were decreased. Moreover, the findings that by spearman analysis Rikenellaceae_RC9_gut_group associated with PD had a significantly negative correlation with phenylalanine (r = -0.488, P < 0.01), tyrosine (r = -0.541, P < 0.01) and isoleucine (r = -0.434, P < 0.01). Conclusions: Our results not only find Rikenellaceae_RC9_gut_group, a new pro-inflammatory genus of intestinal microbiota in PD, but also reveal that it's related to amino acids. These findings are beneficial to identifying microbial therapeutic targets for PD.


2021 ◽  
Vol 93 (2) ◽  
pp. 215-221
Author(s):  
A. A. Iakupova ◽  
S. R. Abdulkhakov ◽  
A. G. Safin ◽  
I. M. Alieva ◽  
Ju. V. Oslopova ◽  
...  

Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.


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