Resistant starch (RS) is one of the bioactive polysaccharides to produce Short-chain fatty acids (SCFAs) in the colon and contributes to allergic diseases including atopic dermatitis (AD). However, the bioactive mechanism of RS relieving AD needs to be elucidated. In this study, RS was prepared using chickpeas. Its microstructure and crystal structure were thoroughly characterized. Chickpea RS significantly improved the clinical symptoms and restored Th1/Th2 immune balance in mice with AD induced by calcipotriol. These benefits were eliminated by antibiotic cocktail treatment, suggesting that gut microbiota mediated the alleviation effects of chickpea RS on AD. Based on metagenomic sequencing and untargeted metabolomic analysis, chickpea RS treatment significantly increased the proportions of Butyricimonas virosa, Bifidobacterium pseudolongum, and Faecalibaculum rodentium, and a total of 206 differential metabolites were altered, especially the increase in propionate and butyrate production. Furthermore, we found that acylated butyrate, but not propionate, improved the pathological characteristics by activating GPR109A, which inhibit the phosphorylation levels of IκB-α, p50, p65, JNK, and p-JNK. Collectively, chickpea RS exhibited the bioactive function for regulating the communication of the gut-skin axis via regulating butyrate production to activate GPR109A.
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