Prevotella-Produced Succinate Alleviates Hepatic Steatosis by Enhancing Mitochondrial Function in Layer-Type Chickens.

Background: A higher abundance of Prevotella species in the gut microbiota is associated with the consumption of high-fiber diets and can be reproduced by dietary supplementation with L-arabinose. The effect of Prevotella and its metabolite succinate on hepatic lipid metabolism remains unclear.

Objectives: This study aimed to elucidate the effects of Prevotella and its metabolite succinate on hepatic steatosis in layer-type pullets.

Methods: In experiment 1, 4-wk-old female layer-type chickens (Isa Brown) were randomly divided into 4 dietary groups and fed a basal diet supplemented with 0%, 2%, 4%, or 6% L-arabinose for 11 wk. In experiments 2 and 3, 10-wk-old chickens were orally administered Prevotella (10⁶ CFU) or fed a diet supplemented with 0.2% sodium succinate for 4 wk. The growth performance, plasma lipid metabolites, hepatic lipid accumulation and gene expression, and cecal microbiota were determined. In in vitro experiment, chicken embryo hepatocytes were treated with Prevotella's metabolites or 0.1 mM succinate in the absence or presence of 4c, a succinate receptor 1 (SUCNR1) inhibitor, or shRNA-PGC1β. Lipid deposition and mitochondrial function were measured. Data were analyzed with a 1-way analysis of variance followed by Tukey's test.

Results: L-arabinose decreased (-68%) hepatic and plasma TG (-52%) and enhanced the abundance of cecal Prevotella (+45-fold) (P < 0.001). Oral administration of Prevotella melaninogenica reduced plasma TG (-22%, P < 0.05) and increased succinate (+66%, P < 0.01). Succinate feeding reduced hepatic (-51%, P < 0.001) and plasma TG (-40%, P < 0.05). Both Prevotella and succinate administration reduced fatty acid synthase (FAS) activity with the induction of mitochondrial function-associated proteins. In vitro experiments showed that Prevotella and succinate alter mitochondrial function and lipid metabolism via SUCNR1, wherein PGC1β plays a critical role.

Conclusions: Succinate produced by Prevotella is a likely metabolite that reduces hepatic lipid deposition by suppressing FAS activity and activating mitochondrial function.