Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR

Abstract

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.

Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection

“…Recently, experimental evidence has linked the effectiveness of FMT for colitis with immunosuppression. FMT therapeutically controlled gut inflammation and colitis via the induction of IL-10 and TGF-β, cytokines critical for Treg cell accumulation in the intestine [67,68]. Whether FMT-directed immunosuppression aids in the recovery from C. difficile requires further investigation.…”

Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease

“…In a separate study, FMT was shown to up-regulate the expression of aryl hydrocarbon receptor (AhR), IL-10 and TGF-β in colon tissues in mice with DSS-induced colitis and was associated with improvement in the severity of colon mucosa injury and histological parameters [102]. This correlated with gut microbial recovery of Lactobacillus and Bifidobacterium species and an increase in tryptophan levels which, as demonstrated by this study, results in differentiation of immune cells in order to promote or regulate the release of anti-inflammatory factors [103][104][105].…”

Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease: An Update

“…Restoring a main ecology of normal organisms contributed to resolving inflammation (Burrello et al, 2019). Wei et al (2018) identified that FMT could alleviate the acute colitis stimulated by DSS in mice and FMT results in the upregulation of not only aryl hydrocarbon receptor (AHR) but also transforming growth factor beta (TGF-b) and IL-10 in colon tissues. Wang et al (2020) carried out a study on active UC patients who received three times FMT from a single donor at an interval of 2-3 months.…”