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.
Highlights
The intestinal mucosa is a complex environment where the host and the gut microbiome establish a mutualistic relationship [1]
Similar to that observed in human inflammatory bowel diseases (IBD) patients, experimental intestinal inflammation was induced
Mucus and feces similar to that observed in human IBD patients, experimental intestinal inflammation was induced derived fromby normobiotic mice were of repeatedly transferred into(DSS, colitic mice1)
Summary
The intestinal mucosa is a complex environment where the host and the gut microbiome establish a mutualistic relationship [1]. Expansion of pro-inflammatory bacteria, such as Enterobacteriaceae and Fusobacteriaceae, and depletion of phyla with anti-inflammatory capabilities, such as Firmicutes, are observed in IBD patients [7]. Intestinal dysbiosis in IBD patients seem to temporally precede intestinal inflammation, as it has been observed in the ileal mucosa of children with treatment-naïve IBD [3]. These observations are mechanistically supported by the capability of dysbiotic microbiota or single commensal bacterial species to induce intestinal inflammation when transferred in germ-free mice [8]
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