Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.

Yapeng Yang,Huicong Zou,Xueying Zhang,Shuaifei Feng,Zhifeng Wu,Wei Cheng,Hong Wei,Xiaojiao Zheng,Yuqing Wang,Jinhui He,Xiang Tan,Bota Cui,Miaomiao Dong,Hang Zhang,Zeyue Zhang,Shiyu Tao

doi:10.3389/fimmu.2022.836542

Abstract

In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including Alistipes putredinis, Akkermansia muciniphila, Bifidobacterium adolescentis, short-chain fatty acids (SCFAs)-producing bacterium Christensenella minuta, and secondary bile acids (SBAs)-producing bacterium Clostridium leptum. In the UC intervention group, the SCFA-producing bacterium Bacteroides stercoris, IBD-related bacterium Ruminococcus gnavus, Enterococcus faecalis, and the conditional pathogen Bacteroides caccae, were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.

Highlights

Inflammatory bowel disease (IBD) is a complicated and chronic intestinal disease, consisting of Crohn’s disease (CD) and ulcerative colitis (UC) [1]
Treatment with 3% DSS led to considerably reduced body weight in mice, and this loss was alleviated by healthy donor (HD) bacterial solution to a greater extent than the UC bacterial solution (Figures 2A, B)
The research data indicated that HD intervention significantly alleviated DSSinduced colitis, as evidenced by the prevention of body weight loss, decreased disease activity index (DAI) and histology score, downregulated the levels of colitis markers MPO [30, 31] and eosinophilic peroxidase (EPO) [32], and regulated cytokine homeostasis by providing more types of anti-inflammatory bacteria and metabolites

Summary

Introduction

Inflammatory bowel disease (IBD) is a complicated and chronic intestinal disease, consisting of Crohn’s disease (CD) and ulcerative colitis (UC) [1]. IBD has been reported to be influenced by genetics, environment, and intestinal microbes [2,3,4], and is characterized by host immune response, destruction of the intestinal barrier, and changes in the intestinal microbial community, accompanied by intestinal bleeding, diarrhea, and weight loss [5, 6]. In IBD patients, antigen invasion can activate the mucosal immune response, causing macrophages to release pro-inflammatory cytokines such as IL-1b, IL-6, IL-8, and TNF-a, and aggravate inflammation [7]. UC mainly affects the superficial layer of colonic mucosa, and histological analysis shows mucosal ulceration and a large amount of inflammatory cell infiltration, which is characterized by an increase in the numbers of CD4+ T lymphocytes, neutrophils, and eosinophils [8, 9]. Methods that target intestinal microbes and their metabolites have potential applications in IBD treatment [16]

Methods

Results

Conclusion