Bile acid-axis dysregulation in MASLD/MASH progression: from metabolic mismatch to inflammatory-fibrotic remodeling.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) arise from overlapping metabolic stress, gut-derived inflammatory input, immune activation, and fibrotic remodeling. Bile acids participate in cholesterol metabolism and lipid absorption, and they also regulate metabolic, intestinal barrier, immune, and inflammatory responses through farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (TGR5/GPBAR1), fibroblast growth factor 19 (FGF19), and related signaling pathways. Accordingly, bile acids may constitute an important interface linking intrahepatic metabolic abnormalities with gut-liver inflammatory crosstalk, although many human findings remain associative and require cautious mechanistic interpretation. This review summarizes bile acid-axis dysregulation in MASLD/MASH, focusing on intrahepatic bile acid synthesis and transport, microbiota-mediated bile acid pool remodeling, intestinal barrier disruption, and the intrahepatic inflammatory-fibrotic niche. We propose that bile acid dysregulation should be interpreted beyond simple increases or decreases in total bile acid levels. Instead, it may reflect a systemic mismatch among bile acid pool composition, compartmental distribution, microbial transformation, and receptor-mediated signaling output. Future studies should integrate multi-compartment bile acid profiling with microbial enzyme activity, intestinal barrier assessment, and tissue-specific receptor signaling to support mechanism-based stratification, treatment-response monitoring, and rational combination strategies.