Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice

Qi Zhao, Man-Yun Dai, Ruo-Yue Huang, Jing-Yi Duan, Ting Zhang, Wei-Min Bao, Jing-Yi Zhang, Shao-Qiang Gui, Shu-Min Xia, Cong-Ting Dai, Ying-Mei Tang (), Frank J. Gonzalez and Fei Li ()
Additional contact information
Qi Zhao: Sichuan University
Man-Yun Dai: Sichuan University
Ruo-Yue Huang: Sichuan University
Jing-Yi Duan: Sichuan University
Ting Zhang: Sichuan University
Wei-Min Bao: The First People’s Hospital of Yunnan Province
Jing-Yi Zhang: The second Affiliated Hospital of Kunming Medical University
Shao-Qiang Gui: The second Affiliated Hospital of Kunming Medical University
Shu-Min Xia: The second Affiliated Hospital of Kunming Medical University
Cong-Ting Dai: The second Affiliated Hospital of Kunming Medical University
Ying-Mei Tang: The second Affiliated Hospital of Kunming Medical University
Frank J. Gonzalez: National Institutes of Health
Fei Li: Sichuan University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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 male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.

Date: 2023
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DOI: 10.1038/s41467-023-37459-z

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