Betaine promotes chicken growth through modulating gut microbiota and FXR-mediated activation of IGF genes.

Betaine is a growth-promoting additive used in both the animal production and microbial fermentation industries. The primary mechanisms by which betaine promotes animal growth are well known through its direct action on the host cells. However, it remains unclear whether betaine exerts its growth-promoting effects in chickens dependent on the gut microbiota. Here, we found that betaine promotes the growth of broiler chickens while enhancing the richness and diversity of the cecal microbiota and increasing beneficial bacteria, such as Lactobacillus, Limosilactobacillus, and Prevotella (P < 0.05). However, the growth-promoting effects of betaine were abolished in broilers treated with an antibiotic cocktail. Furthermore, fecal microbiota transplantation from betaine-supplemented chickens could recapitulate the promoting effect of betaine on body weight, breast muscle weight, and hepatic insulin-like growth factors (IGFs) synthesis (P < 0.05), indicating that the gut microbiota plays an indispensable role in betaine's growth-promoting action. Mechanistically, betaine promotes (P < 0.05) the synthesis of bile acids, and microbial function predictions suggest that betaine upregulates the biosynthetic pathways of primary and secondary bile acids. Notably, the expression of the bile acid receptor farnesoid X receptor (FXR) was upregulated (P < 0.05) in the liver, promoting FXR binding to the IGFs genes promoter regions and activating the transcription of IGFs gene. Taken together, our findings suggest that betaine promotes broiler growth via microbiota-dependent mechanisms, accompanied by FXR-mediated upregulation of IGFs gene expression in the liver, providing new perspectives and theoretical support for understanding the complexity of animal growth regulation.