Gut microbiota ameliorates hepatic fibrosis through modulating intestinal bile acid metabolism and hepatocyte pyroptosis (Hepatic fibrosis serum+feces)

ABSTRACT:

Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to mice improves thioacetamide (TAA)- and methionine and choline deficient (MCD) diet-induced hepatic fibrosis. P. distasonis was associated with increased bile salt hydrolase (BSH) activity and inhibition of intestinal farnesoid X receptor (FXR) signaling leading to decreased taurochenodeoxycholic acid (TCDCA) levels in liver. The decrease of TCDCA improved activation of hepatic stellate cells (HSCs) through decreasing the mitochondrial permeability transition (MPT)-Caspase-11 pyroptosis pathway. Celastrol was demonstrated as a promoter of P. distasonis, which could inhibit intestinal FXR and increase the excretion of bile acids, leading to decreased hepatic TCDCA and prevention against TAA- and MCD diet-induced hepatic fibrosis. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.

Hepatic fibrosis serum+feces (sample 3) analysis is reported in the current study MTBLS6728.

Hepatic fibrosis serum (sample 1) analysis is reported in MTBLS6732.

Hepatic fibrosis feces (sample 2) analysis is reported in MTBLS6742.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase

PROVIDER: MTBLS6728 | MetaboLights | 2023-03-17

REPOSITORIES: MetaboLights