Dataset Information

Microbial metabolites indole derivatives sensitize mice to D-GalN/LPS induced-acute liver failure via the Tlr2/NF-κB pathway.

ABSTRACT:

Introduction

Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge.

Methods

To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites.

Results

Contrary to their typical role as anti-inflammatory agents in the host, indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indolepropionic acid (IPA) gavage sensitize mice to D-GalN/LPS-induced-ALF with a rapid rise in serum transaminases and histologic lesion. For a clearer picture, we performed comprehensive analysis for the IAA therapy. IAA markedly amplified inflammatory response and cellular damage. The transcriptome analysis indicated the participation of the TNF-α/NF-κB signaling pathway. The structure of gut microbiota in ileum and the expression of Toll-like receptor 2 (Tlr2) in the liver were also significantly changed.

Discussion

In conclusion, IAA pretreatment can exacerbate D-GalN/LPS-induced ALF via probable Tlr2/NF-κB pathway involvement and ileac dysbiosis characterized by enriched gram-positive genus with potential pathogenesis. Microbial metabolites IAA may aggravate individual susceptibility to D-GalN/LPS-induced ALF. Further investigation of the underlying mechanism is needed, and intervention with indole derivatives and related commensal species should be undertaken with caution.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC9852867 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Microbial metabolites indole derivatives sensitize mice to D-GalN/LPS induced-acute liver failure <i>via</i> the Tlr2/NF-κB pathway.

Zhou Ziyuan Z Wang Baohong B Pan Xiaxia X Lv Jiawen J Lou Zhuoqi Z Han Yuqiu Y Yao Yuanyuan Y Chen Jun J Wang Qiangqiang Q Li Lanjuan L

Frontiers in microbiology 20230106

<h4>Introduction</h4>Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge.<h4>Methods</h4>To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites.<h4>Results</h4>Contrary to their typica ...[more]

PMID: 36687651

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