Receptor-targeted next-generation probiotics ameliorate inflammation and promote gut health

Background: Intestinal barrier dysfunction, inflammation, and elevated expression of heat shock protein 60 (Hsp60) are features of the dysbiotic gut. Probiotics can alleviate inflammation but are ineffective due to poor adhesion and adaptation to the inflamed bowel. We hypothesize that enhancing probiotic adhesion to intestinal cells may augment the immunomodulatory response, mucosal healing, and tight junction restoration. Earlier, we identified Listeria adhesion protein (LAP; 94-kDa) that aids Listeria attachment to the epithelial cells by interacting with Hsp60. Next-generation bioengineered Lactobacillus casei (Lbc) probiotics (BLP) expressing LAP from L. innocua showed strong interaction with epithelial Hsp60, high immunomodulatory response, and epithelial barrier integrity while reducing inflammation.

Method: We fed BLP for 10 d to mice pretreated with dextran sulfate sodium (DSS, 2% for 7 d), as a chemically induced inflamed gut model.

Results: BLP-fed DSS-treated mice gained 5% body weight compared with the DSS-treated mice that did not receive any probiotics during that period. BLP feeding conferred a 67% reduction in disease activity index compared with the control and 50% to LbcWT-treated mice. BLP treatment restored fecal consistency to Type 3–4 (Bristol scoring) within 9 d of feeding, while the control and LbcWT treatment groups failed. BLP-fed mice showed improved gut barrier; > 50% reduction in FITC-labeled 4-kDa dextran (FD4) permeability compared with LbcWT or the control group. DSS-induced shortened colon length, abdominal adhesions, and mucus accumulation were substantially improved by BLP feeding relative to the control and LbcWT groups. Colon pathology, including neutrophil infiltration of the BLP-fed group, was 50% lower than the LbcWT group. BLP-fed mice also showed reduced Hsp60 expression compared with the control groups.

Conclusions: BLP feeding ameliorated gut inflammation, thus offering a potential dietary supplement for reducing gut-associated inflammation and improving gut health in livestock.

Key Words: Next-generation probiotics, Listeria adhesion protein, inflammation.