Plasma and fecal bile acids profiles in metabolic dysfunction-associated steatotic liver disease with advanced fibrosis.

Bile acids (BAs) act as hormonal ligands of hepatic and intestinal receptor FXR, stimulators of FGF-19 and GLP-1 secretion. While MASLD is linked to BA dysregulation, the effects of advanced fibrosis on plasma and fecal BA profiles remain unclear. We compared 35 plasmatic and fecal BA concentrations and qualitative pools, including primary, secondary, unconjugated and conjugated BAs in fasting state between individuals with advanced fibrosis stages (F3-F4/4) (n=28) and individuals without advanced fibrosis (n=26). Median age (IQR) (56 [48-65] vs 57 [49-66] yr), sex (62 vs 60% man) and BMI (32 [29-36] vs 34[32-38] kg/m 2 ) were comparable between groups. Total plasmatic BA concentration was increased in the advanced stage of fibrosis (p<0.01), whereas total stool BA concentration did not differ between groups (p = 0.36). Participants with advanced fibrosis had higher CDCA family BAs, which was driven by increased glyco- and tauro-conjugated forms (p<0.05). Plasma unconjugated secondary BA LCA was also higher in advanced fibrosis (p<0.01), but we did not find change in intestinal microbiota BSH enzymatic activity, responsible for deconjugation of BA. There were no differences in FGF-19 and GLP-1 concentrations between groups. Overall, our results lead us to hypothesize that the increase in hepatic bile acid production in cases of MASLD with advanced fibrosis may occur mainly via the acid pathway, or leakage of BAs from the liver into the plasma caused by hepatic inflammation, without changes in intestinal BA metabolism. This profile of increased hydrophobic plasma BA may contribute to MASLD progression, inflammation and oxidative stress.