Diet-rich in wheat bran modulates tryptophan metabolism and AhR/IL-22 signalling mediated metabolic health and gut dysbacteriosis: A novel prebiotic-like activity of wheat bran

Tryptophan metabolism has shown to involve in pathogenesis of various metabolic diseases. Gut microbiota-orientated diets hold great potentials to improve metabolic health via regulating tryptophan metabolism. The present study showed that the 6-week high fat diet (HFD) disturbed tryptophan metabolism accompanied with gut dysbacteriosis, also influenced the dietary tryptophan induced changes in cecum microbiome and serum metabolome in mice. The colonic expressions of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) were significantly reduced in mice fed on HFD. Notably, a diet- rich in wheat bran effectively inhibited transformation of tryptophan to kynurenine-pathway metabolites, while increased melatonin and microbial catabolites, i.e. indole-3-propionic acid, indole-3-acetaldehyde and 5-hydroxy-indole-3-acetic acid. Such regulatory effects were accompanied with reduced fasting glucose and total triglycerides, and promoted AhR and IL-22 levels in HFD mice. Wheat bran increased the abundance of health promoting bacteria (e.g., Akkermansia and Lactobacillus), which were significantly correlated with tryptophan derived indolic metabolites. Additionally, beneficial modulatory effects of wheat bran on indolic metabolites in associations with gut dysbacteriosis from type 2 diabetes patients were confirmed in vitro fecal fermentation experiment. Our study proves the detrimental effects of HFD induced gut dysbacteriosis on tryptophan metabolism that may influence immune modulation, and provides novel insights in the mechanisms by which wheat bran could induce health benefits.