Table 2.

Therapy targeting bile acid–gut microbiota axis for inflammatory bowel disease.

Publication	Subjects	Treatment	Samples and Methods	Major Findings
Diederen et al., 2020 [39]	43 pediatric patients with CD and 18 healthy controls	EEN for 6 weeks followed by 2 weeks of EEN tapering	Fecal samples (16S rRNA sequencing and HPLC)	EEN decreased the microbiota diversity and reduced trimethylamine and cadaverine towards control levels. Reduced microbial metabolism of BAs in CD was partially normalized during EEN.
Paramsothy et al., 2019 [88]	81 patients with active UC	FMT or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks	Fecal samples (metagenomic and metabolomic analysis) Colonic biopsy samples (16S rRNA gene and transcript sequencing)	Microbial diversity was increased and the composition was altered after FMT. The patients in remission had enriched Eubacterium hallii and Roseburia inulivorans. Mucosal microbiota showed increased α-diversity after FMT. Patients in remission had increased levels of secondary BA (dehydrolithocholate).
Wang et al., 2021 [19]	29 pediatric CDs	Infliximab infusion for 3–6 times	Fecal samples (16S rRNA sequencing and UPLC-MS)	The abundances of Blautia, Clostridium IV, Collinsella, Eubacterium and Ruminococcus were increased after treatment. The ratios of unconjugated/conjugated BAs and secondary/primary BAs were elevated.
Wang et al., 2019 [89]	Canine model of chronic inflammatory enteropathy	Hydrolyzed protein diet for 6 weeks	Fecal samples (metagenomic and metabolomic analysis)	Gut microbiota was restored, as marked by reduced pathogens and increased Clostridium hiranonis after treatment. The levels of secondary BAs (LCA and DCA) were increased after treatment.
Ke et al., 2020 [90]	Mice with DSS-induced chronic colitis	Fucose gavage for 57 days	Ileal tissue lysates and colonic feces (16S rRNA sequencing and UPLC-MS)	Fucose increased α-diversity and reversed the decreased ratio of Firmicutes to Bacteroidetes. The level of tauro-β-MCA and TCA was decreased and the abnormal ratio of conjugated/unconjugated BAs was restored after treatment.
Jia et al., 2020 [91]	Mice with DSS-induced acute colitis	Oral total alkaloids of Sophora alopecuroides L. for 7 days	Cecum content (16S rDNA gene sequencing) Liver, bile, serum, cecum content and colon samples (UPLC-MS)	The abundance of Firmicutes was increased, whereas that of Bacteroidetes was decreased after treatment. The elevated MCAs and CA were restored after treatment.
Bossche et al., 2017 [12]	Mice with DSS-induced acute colitis	Daily gavage of UDCA, TUDCA, GUDCA or placebo for 10 days	Fecal samples (16S rRNA sequencing and HPLC)	The ratio of Firmicutes/Bacteroidetes was normalized and the abundance of Clostridium cluster XIVa and Akkermansia muciniphila was increased. The concentrations of UDCA, TUDCA and LCA were remarkably elevated after treatments.

Abbreviations: FMT, fecal microbiota transplantation; EEN, exclusive enteral nutrition; IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; DSS, dextran sulfate sodium; BA, bile acid; HPLC, high-performance liquid chromatography; UPLC-MS, ultraperformance liquid chromatography coupled with mass spectrometry; MCA, muricholic acids; CA, cholic acid; TCA, taurocholic acid; UDCA, ursodeoxycholic acid; TUDCA, tauroursodeoxycholic acid; GUDCA, glycoursodeoxycholic acid; DCA, deoxycholic acid; LCA, lithocholic acid.