β-Casein hydrolysate generated by the cell envelope-associated proteinase of Lactobacillus delbrueckii ssp lactis CRL 581 protects against trinitrobenzene sulfonic acid-induced colitis in mice

Lactobacillus delbrueckii ssp. lactis CRL 581, a thermophilic lactic acid bacterium used as a starter culture for the manufacture of several fermented dairy products, possesses an efficient proteolytic system that is able to release a series of potentially bioactive peptides (i.e., antihypertensive and phosphopeptides) from alpha- and beta-caseins. Considering the potential beneficial health effects of the peptides released by L. delbrueckii ssp. lactis CRL 581 from milk proteins, the aim of this work was to analyze the anti-mutagenic and anti-inflammatory properties of the casein hydrolysates generated by the cell envelope-associated proteinase of this bacterium. The ability of alpha- and beta-casein hydrolysates to suppress the mutagenesis of a direct-acting mutagen 4-nitroquinoline-N-oxide on Salmonella typhimurium TA 98 and TA 100 increased concomitantly with the time of casein hydrolysis. The anti-inflammatory effect of the beta-casein hydrolysate was evaluated using a trinitrobenzene sulfonic acid (TNBS)-induced Crohn's disease murine model. The hydrolysate was administered to mice 10 d before the intrarectal inoculation of TNBS. The mice that received beta-casein hydrolysate previously to TNBS showed decreased mortality rates, faster recovery of initial body weight loss, less microbial translocation to the liver, decreased beta-glucuronidase and myeloperoxidase activities in the gut, and decreased colonic macroscopic and microscopic damage compared with the animals that did not receive this hydrolysate. In addition, beta-casein hydrolysate exerted a beneficial effect on acute intestinal inflammation by increased interleukin 10 and decreased IFN-gamma production in the gut. Our findings are consistent with the health-promoting attributes of the milk products fermented by L. delbrueckii ssp. lactis CRL 581 and open up new opportunities for developing novel functional foods.