Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Abstract

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

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

“…Phenotypically, FMT-treated mice show lower percentages of CD 8+ T and CD 4+ T cells, which express the cytotoxicity-related molecule CD107a. This further supports the observation of a decrease in the pro-inflammatory phenotype of colonic T cells in mice treated with FMT (Burrello et al, 2019).…”

“…It is not known if tissue impairment is caused by abnormal immune responses to normal microbiota or by a normal immune response to abnormal microbiota or if dysbiosis constitutes a cause or outcome of IBD (Sheehan et al, 2015;Ni et al, 2017). FMT is considered a promising therapeutic methodology for IBD patients, primarily to achieve outcomes of intestinal microbial restoration (Burrello et al, 2019). FMT can increase the diversity of intestinal microorganisms, together with rebuilding the immune system and maintaining the balance of intestinal microecology.…”

Recent updates on the basic mechanisms and pathogenesis of inflammatory bowel diseases in experimental animal models

“…Recent studies on both acute and chronic experimental colitis showed that the therapeutic effects of FMT are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. 94,95 Specifically, expression of pro-inflammatory genes, antimicrobial peptides, and mucins were observed to decrease in animals receiving the treatment.…”

Microbial Changes Associated with IBD Mouse Model and Microbiota Transplantation Confers Colitis Symptom in Microbiota Deletion Mice

“…Combining FMT and antibiotics contributed to the microbiological improvement of intestinal dysbiosis in UC patients [23]. Previous study found the microbiota could alleviate murine chronic intestinal inflammation through modulating immune cell functions in terms of FMT [24].…”