Fish protein hydrolysates and peptides alleviate colitis via regulating gut microbiota

Sturgeon muscle byproducts collected after caviar production are usually not fully utilized, and sometimes may be discarded, thus causing a lot of waste. Yet dietary protein hydrolysates, which may be derived from sturgeon muscle, have been reported to have versatile beneficial biological activities. Our study suggests that sturgeon muscle-derived hydrolysates significantly decreased the severity of DSS-induced damage, and partially restored the alteration of the gut microbiota in colitic mice. Further study elucidated the therapeutic mechanisms of novel sturgeon-derived peptide (LLLE, Leu-Leu-Leu-Glu) on intestinal inflammation via regulating gut microbiota composition and fecal metabolites in a mouse model of inflammatory bowel disease (IBD). LLLE administration alleviated weight loss and disease activity index (DAI) scores in dextran sulfate sodium salt (DSS)-induced colitis in mice. Histopathological examination showed LLLE pretreatment improved colon morphology and histopathological condition and decreased serum interleukin-6 (IL-6) levels. 16S rRNA sequencing indicated LLLE-modulation of gut microbiota, especially alleviated DSS-elevated Bacteroidetes. Fecal metabolomic analysis unveiled that LLLE restored critical metabolites such as indole-3-propionic acid, which is pivotal in anti-inflammatory responses. Altogether, sturgeon peptide exhibits considerable promise as a therapeutic agent for colitis, owing to its anti-inflammatory effects, modulation of gut microbiota, and restoration of essential fecal metabolites.