Butyrylated Smilax glabra starch relieves atopic dermatitis through gut–skin axis modulation via colon-targeted delivery

Atopic dermatitis (AD) is a prevalent cutaneous condition with chronic inflammation and immune dysregulation, posing a public health concern owing to its long-lasting and recurrent nature. Butyrate, a short-chain fatty acid produced by gut microbiota, exhibits significant anti-inflammatory effects in AD. Yet, its delivery <i>via</i> butyrylated starch for prolonged release in the colon has not been adequately investigated. In this study, butyrylated <i>Smilax glabra</i> starch (BSGS) was synthesized and its therapeutic potential against AD <i>via</i> modulation of the gut-skin axis was examined. BSGS exhibited a C-type crystalline structure and highly resistance to gastrointestinal digestion. <i>In vitro</i> anaerobic fermentation showed that BSGS effectively promoted the generation of short-chain fatty acids, especially butyrate, and positively influenced the gut microbial composition. In AD mice, BSGS administration considerably mitigated cutaneous inflammation, lowered serum proinflammatory cytokines, restored intestinal barrier integrity, and modulated gut microbiota by increasing <i>Bacteroides</i> and <i>norank_f__Prevotellaceae</i> while decreasing <i>Alistipes</i> and <i>norank_o__RF39</i>. This therapeutic effect was associated with butyrate release and NF-<i>κ</i>B pathway suppression, as evidenced by the reduced phosphorylation of p65 and I<i>κ</i>B<i>α</i>. These findings establish that BSGS, a novel colon-targeted butyrate donor, holds promising potential in AD treatment by modulating the immune system <i>via</i> the gut-skin axis.