Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation

Abstract

Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.

Keywords: Fecal microbiota transplantation; Gut microbiome; Host immunity; Inflammatory bowel disease; Metabolome.