Altered profiles of fecal bile acids correlate with gut microbiota and inflammatory responses in patients with ulcerative colitis

Abstract

BACKGROUND Gut microbiota and its metabolites may be involved in the pathogenesis of inflammatory bowel disease. Several clinical studies have recently shown that patients with ulcerative colitis (UC) have altered profiles of fecal bile acids (BAs). It was observed that BA receptors Takeda G-protein-coupled receptor 5 (TGR5) and vitamin D receptor (VDR) participate in intestinal inflammatory responses by regulating NF-ĸB signaling. We hypothesized that altered profiles of fecal BAs might be correlated with gut microbiota and inflammatory responses in patients with UC. AIM To investigate the changes in fecal BAs and analyze the relationship of BAs with gut microbiota and inflammation in patients with UC. METHODS The present study used 16S rDNA sequencing technology to detect the differences in the intestinal flora between UC patients and healthy controls (HCs). Fecal BAs were measured by targeted metabolomics approaches. Mucosal TGR5 and VDR expression was analyzed using immunohistochemistry, and serum inflammatory cytokine levels were detected by ELISA. RESULTS Thirty-two UC patients and twenty-three HCs were enrolled in this study. It was found that the diversity of gut microbiota in UC patients was reduced compared with that in HCs. Firmicutes , Clostridium IV , Butyricicoccus , Clostridium XlVa , Faecalibacterium , and Roseburia were significantly decreased in patients with UC ( P = 3.75E-05, P = 8.28E-07, P = 0.0002, P = 0.003, P = 0.0003, and P = 0.0004, respectively). Proteobacteria , Escherichia , Enterococcus , Klebsiella , and Streptococcus were significantly enriched in the UC group ( P = 2.99E-09, P = 3.63E-05, P = 8.59E-05, P = 0.003, and P = 0.016, respectively). The concentrations of fecal secondary BAs, such as lithocholic acid, deoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, and taurolithocholate, in UC patients were significantly lower than those in HCs ( P = 8.1E-08, P = 1.2E-07, P = 3.5E-04, P = 1.9E-03, and P = 1.8E-02, respectively) and were positively correlated with Butyricicoccus , Roseburia , Clostridium IV , Faecalibacterium , and Clo...

Bile Acid–Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside

“…In patients with CD, the abundance of Erysipelotrichales , Bacteroidales and Clostridiales , Ruminococcaceae and Lachnospiraceae families and Faecalibacterium prausnitzii was reduced, whereas that of Enterobacteriaceae , such as E. coli , Pasteurellacaea , Veillonellaceae , and Fusobacteriaceae families, was elevated [ 14 , 17 , 18 , 19 ]. In patients with UC, reductions in Clostridium XIVa, Butyricicoccus , Eubacterium rectale , F. prausnitzii and Roseburia hominis of the Ruminococcaceae and Lachnospiraceae families were found, whilst Ruminococcus gnavus , Clostridium ramosum and E. coli were enriched [ 20 , 21 , 22 ]. Intriguingly, some beneficial bacteria, such as F. prausnitzii and R. hominis , are SCFA-producing bacteria and they play vital roles in bile acid metabolism.…”

“…They found that the secondary bile acids, such as LCA, DCA and tauro-LCA were reduced significantly in UC compared with healthy controls and were positively related to Faecalibacterium , Roseburia , Butyricicoccus and Clostridium . The primary and conjugated bile acids (CA, TCA and G/TCDCA) were elevated and were positively correlated with Enterococcus , Klebsiella and Streptococcus [ 22 ].…”

Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis

“…Furthermore, recent work has attempted to identify a link between the metabolic function of the gut microbiota and UC (25). Numerous results indicate involvement of bile acids (BAs) in IBD and recovery, in particular their transformation to secondary BAs by microbes (26)(27)(28)(29)(30)(31)(32)(33)(34). Paired BA metabolomics with metagenomic sequencing before, during, and after FMT might help to elucidate the importance of these signalling compounds in UC treatment (1,25).…”

Disordered Gut Microbiota Correlates With Altered Fecal Bile Acid Metabolism and Post-cholecystectomy Diarrhea

“…Furthermore, we demonstrated tight associations between bile acid metabolites and gut microbiota in this study, notably Prevotella and TUDCA. Positive correlations indicated that overabundant bile acids favor bacterial growth, for example, Enterococcus and CDCA in ulcerative colitis (Yang et al, 2021), but negative associations for detrimental effects, for example, reduced Alistipes and Bacteroides with total bile in IBS-D patients (Zhao et al, 2020). Besides, UCG-002, Klebsiella, and Escherichia-Shigella were also closely correlated with these bile salts, despite the fact that no significant difference of relative abundance was achieved among three groups.…”