Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming

Abstract

Fecal microbiota transplantation (FMT) is gaining attention for the treatment of ulcerative colitis (UC). Data from individual case studies have suggested that FMT may be beneficial for UC, but the detailed microbial and molecular basis remains unknown. Here, we employ 16S rRNA gene sequencing and metabolomics to investigate the influence of FMT on gut microbial community composition and host metabolism in the dextran sulfate sodium-induced UC rat model. The findings from this pilot study suggest that FMT from normal donors to UC recipients could alleviate UC symptoms without close resemblance of donor's gut microbial and metabolic pattern. Meanwhile, FMT from UC donors to normal recipient rats triggered UC symptoms, UC-prone microbial shift, and host metabolic adaption. Gut microbiota under normal conditions could maintain stable species richness and diversity upon FMT intervention, but the disturbed gut microbiota under UC conditions could not maintain such homeostasis. Significant correlations between altered bacterial composition and host metabolism could be assigned to the pathological effects of UC (accounting for 8.0 to 16.2% of total variance) and/or the FMT intervention effects (3.9 to 7.0% of total variance). Overall, our study reveals diverse gut microbial shifts in UC related FMT and their association with host metabolic reprogramming. This study combined clinical symptoms measurement, 16S rRNA gene microbial profiling and metabolomics to comprehensively investigate the gut bacterial and host metabolic association and reprogramming in FMT-treated experimental UC. These data can advance our understanding of the effect of FMT on UC and the involvement of gut microbial dysbiosis in the development of UC.

Sargassum fusiforme Polysaccharides Prevent High-Fat Diet-Induced Early Fasting Hypoglycemia and Regulate the Gut Microbiota Composition

“…Microbiome data were analyzed according to our previous study [35], with minor modifications. Briefly, data processing, normalization, scaling, and multivariate analyses were performed using the R package MetaboAnalystR [36].…”

Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study

“…In particular, the Desulfovibrio and Clostridium genera have been closely linked to UC [6]. Thus, the development of UC is closely related to changes in the intestinal flora [7][8][9][10][11].…”

Mechanisms underpinning the efficacy of faecal microbiota transplantation in treating gastrointestinal disease

“…It was noted that hippuric acid decreased in the normal rats but was restored to normal levels at day 6 and 7, and further found that the changes induced by FMT correlated with the genera Oscillospira and Dehalobacterium and the families Bacillaceae and Exiguobacteraceae. 52 Importantly it has been shown that hippuric acid is reduced in CD and UC due to gut microbial metabolism; this therefore suggests that FMT can alter the gut microbiome to change the metabolic drivers of disease states. 53 Further supporting this concept was a study on pigs, where it was noted that FMT resulted in significant increases of the typical microbiotaderived tryptophan catabolite indole-3-acetic acid in the colonic lumen, 54 suggesting that tryptophan metabolites may be important actors in the efficacy of FMT.…”