Abstract
Alpha-ketoglutarate (AKG), a precursor of glutamate and a critical intermediate in the tricarboxylic acid cycle, shows beneficial effects on intestinal function. However, the influence of AKG on the intestinal innate immune system and intestinal microbiota is unknown. This study explores the effect of oral AKG administration in drinking water (10 g/L) on intestinal innate immunity and intestinal microbiota in a mouse model. Mouse water intake, feed intake and body weight were recorded throughout the entire experiment. The ileum was collected for detecting the expression of intestinal proinflammatory cytokines and innate immune factors by Real-time Polymerase Chain Reaction. Additionally, the ileal luminal contents and feces were collected for 16S rDNA sequencing to analyze the microbial composition. The intestinal microbiota in mice was disrupted with an antibiotic cocktail. The results revealed that AKG supplementation lowered body weight, promoted ileal expression of mammalian defensins of the alpha subfamily (such as cryptdins-1, cryptdins-4, and cryptdins-5) while influencing the intestinal microbial composition (i.e., lowering the Firmicutes to Bacteroidetes ratio). In the antibiotic-treated mouse model, AKG supplementation failed to affect mouse body weight and inhibited the expression of cryptdins-1 and cryptdins-5 in the ileum. We concluded that AKG might affect body weight and intestinal innate immunity through influencing intestinal microbiota.
Highlights
Alpha-ketoglutarate (AKG) is a keto acid synthesized by deamination of glutamate (Glu) and an important intermediate of the tricarboxylic acid cycle
Recent compelling investigations have shown that glutamine (Gln) and arginine (Arg), which can convert to AKG indirectly, regulate intestinal innate immunity by activating multiple signaling pathways and modulating the intestinal microbiota in a mouse model [10, 11]
The results demonstrated that AKG supplementation lowers body weight and influences the variety and composition of the intestinal microbiota in addition to intestinal innate immunity, such as promoting ileal expression of mammalian defensins of the alpha subfamily
Summary
Alpha-ketoglutarate (AKG) is a keto acid synthesized by deamination of glutamate (Glu) and an important intermediate of the tricarboxylic acid cycle. It has various physiological functions, including acting as an antioxidant [1, 2] or as an anticancer agent [3, 4]. Recent compelling investigations have shown that glutamine (Gln) and arginine (Arg), which can convert to AKG indirectly, regulate intestinal innate immunity by activating multiple signaling pathways and modulating the intestinal microbiota in a mouse model [10, 11]. The results demonstrated that AKG supplementation lowers body weight and influences the variety and composition of the intestinal microbiota in addition to intestinal innate immunity, such as promoting ileal expression of mammalian defensins of the alpha subfamily
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