Host miRNA-21 promotes liver dysfunction by targeting small intestinal Lactobacillus in mice

Area of Science:

• Microbiology
• Molecular Biology
• Hepatology

Background:

• Host-microbiota interactions are crucial for health and disease.
• Endogenous microRNAs (miRNAs) can modulate these interactions.
• Previous work indicated miR-21 ablation protects against cholestatic liver injury.

Purpose of the Study:

• To investigate the role of miR-21 in gut microbiota modulation during cholestasis.
• To determine the effect of miR-21 on liver dysfunction in cholestasis.
• To explore the therapeutic potential of Lactobacillus supplementation.

Main Methods:

• Utilized miR-21 knockout (miR-21KO) mice subjected to bile duct ligation (BDL) surgery.
• Analyzed gut microbiota composition and liver/intestinal injury.
• Performed in vitro incubation of synthetic miR-21 with Lactobacillus and in vivo supplementation with Lactobacillus reuteri.

Main Results:

• miR-21KO mice exhibited reduced liver and small intestinal injury, and protected against gut microbiota dysbiosis post-BDL.
• miR-21KO mice showed an increase in Lactobacillus, a genus vital for gut homeostasis.
• In vitro miR-21 reduced Lactobacillus load; Lactobacillus reuteri supplementation mimicked miR-21KO protective effects against liver fibrosis.

Conclusions:

• miR-21 promotes liver dysfunction by directly modulating the gut microbiota composition.
• Lactobacillus, particularly Lactobacillus reuteri, plays a protective role in cholestasis-induced liver injury and fibrosis.
• Lactobacillus supplementation represents a potential therapeutic avenue for restoring gut and liver homeostasis.