Bile Acid Sequestration Attenuates Desulfovibrio-Induced Hepatic Injury

TL;DR

This study shows that bile acid sequestration can reduce liver damage caused by gut bacteria called Desulfovibrio.

Contribution

The study demonstrates that bile acid sequestration mitigates Desulfovibrio-induced liver injury through microbial and metabolic mechanisms.

Findings

Bile acid sequestration with cholestyramine reduces Desulfovibrio-induced liver inflammation and damage.

Desulfovibrio alters gut microbiota composition, which is reversed by bile acid sequestration.

Bile acid dynamics are central to both liver injury and gut microbial community changes.

Abstract

Desulfovibrio (DSV), sulfate-reducing gut bacteria that generate hydrogen sulfide (H2S), can impact host health through diverse mechanisms including bile acid (BA) metabolism. Although intestinal overgrowth of DSV expands the BA pool and promotes liver injury, its causal role in hepatic pathophysiology remains incompletely defined. Here, by employing complementary interventions of cholic acid (CA) supplementation and the BA sequestrant cholestyramine in mouse models, we show that DSV-driven liver injury is mediated by aberrant BA metabolism coupled with gut microbial remodeling. CA alone induced overt hepatic damage, whereas supplemental DSV did not further exacerbate injury caused by excessive CA. Intervention with the BA sequestrant cholestyramine markedly attenuated DSV-elicited hepatic inflammatory and histological alterations, which were associated with an upregulation of the intestinal BAs pool. Hepatic expression of BAs synthetic genes Cyp7a1 and Cyp8b1 verified a negative-feedback regulation of BA metabolism upon treatments. 16S rRNA gene sequencing revealed that CA, DSV, and the cholestyramine all significantly influenced the gut microbiota. CA reduced microbial richness and drove community separation, while DSV intervention under high BA conditions enriched specific biomarkers including Eubacterium ventriosum and Enterorhabdus. Notably, the administration of cholestyramine attenuated these DSV-associated microbial shifts and further reduced overall species richness, confirming the integral role of BA dynamics in shaping the gut microbial community. Collectively, our research reveals the intricate link between DSV, BAs, and gut microbiota in liver injury, and suggests that modulation of BAs may hold therapeutic potential for DSV-associated liver hepatic conditions.

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