Page 13 - Read Online

Page 8 of 13 Zhao et al. Microbiome Res Rep. 2025;4:28 https://dx.doi.org/10.20517/mrr.2025.12

Figure 1. Potential therapeutic role of targeting microbial BSH expression in MASLD. MASLD: Metabolic dysfunction-associated
steatotic liver disease; BSH: bile salt hydrolase; T-β-MCA: tauro-β-muricholic acid; FXR: farnesol X receptor; conBAs: conjugated bile
acids; unconBAs: unconjugated bile acids; BAT: brown adipose tissue.

MASLD . Microbial BSH influences the composition and concentration of secBAs, which can in turn
[7]
modulate FXR and TGR5 signaling pathways.

Importantly, FXR exhibits tissue-specific effects - acting differently in the liver and intestine. Intestinal BSH
inhibition can lead to the accumulation of endogenous FXR antagonists, thereby helping to restore
[46]
metabolic balance in the gut. Several studies have reported that BSH inhibitors , antioxidants , and
[17]
natural compounds can reduce microbial BSH expression and/or activity in mouse models, resulting in
[47]
increased levels of T-β-MCA, an endogenous FXR antagonist. This suppression of FXR signaling in ileal
epithelial cells reduces ceramide synthesis and promotes GLP-1 secretion, ultimately improving metabolic
outcomes. Conversely, supplementation with BSH-active Lactobacillus plantarum increases CDCA levels,
which suppress hepatic lipogenesis and insulin resistance via FXR signaling. Activation of hepatic FXR
[48]
[49]
inhibits triglyceride production by downregulating the SREBP-1c lipogenesis pathway . Additionally, FXR
agonists such as obeticholic acid have been shown to promote brown fat differentiation and energy
[50]
metabolism .