Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colorectum, posing a significant global health burden. Recent studies highlight the critical role of gut microbiota and its metabolites, particularly bile acids (BAs), in UC's pathogenesis. The relationship between BAs and gut microbiota is bidirectional: microbiota influence BA composition, while BAs regulate microbiota diversity and activity through receptors like Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Targeting bile-acid metabolism to reshape gut microbiota presents a promising therapeutic strategy for UC. This review examines the classification and synthesis of BAs, their interactions with gut microbiota, and the potential of nutritional and microbial interventions. By focusing on these therapies, we aim to offer innovative approaches for effective UC management.

Keywords: bile acids; microbiota; nutrition; ulcerative colitis.

Figure 1

Summary of current status of ulcerative colitis. UC: ulcerative colitis; CRC: colorectal cancer; DALYs: disability-adjusted life years.

Figure 2

Metabolism of bile acids (BAs) in humans and in mice. BAs are synthesized in the liver from cholesterol, involving CYP7A1, CYP27A1, and CYP8B1. Conjugated BAs are transported to the gallbladder via the bile salt export pump (BSEP). In the gut, bile salt hydrolase (BSH) enzymes produced by microbiota deconjugate BAs. Primary BAs are converted into secondary BAs by gut bacteria. Secondary BAs are absorbed into the bloodstream and transported back to the liver, completing the enterohepatic circulation.

Figure 3

FXR and TGR5 regulate inflammation and immune responses. BAs activate FXR, leading to the regulation of tight junction proteins (TJs), including claudin and occludin. This strengthens the intestinal barrier and reduces bacterial translocation (BT); FXR activation also inhibits inflammatory signaling pathways, such as AP-1 and NF-κB, thereby reducing the production of pro-inflammatory cytokines like TNF-α. TGR5 activation modulates macrophage polarization, promoting a shift from the pro-inflammatory M1 phenotype (producing IFN-γ and TNF-α) to the anti-inflammatory M2 phenotype (producing IL-10).