42 Remodeling intestinal barrier damage and gut microbiome by bioengineered probiotics

Abstract Intestinal barrier dysfunction, inflammation, and increased 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 hypothesized that enhancing probiotic adhesion to intestinal cells may augment the immunomodulatory response, mucosal healing, tight junction restoration, and microbiome remodeling. Listeria adhesion protein (LAP; 94-kDa), also known as alcohol acetaldehyde dehydrogenase, aids Listeria attachment to the epithelial cells by interacting with Hsp60 and was cloned and expressed on Lactobacillus casei (Lbc). This bioengineered probiotic showed strong interaction with epithelial Hsp60, greater immunomodulatory response, and epithelial barrier integrity while reducing inflammation in a chemically (dextran sulfate sodium)-induced damaged, inflamed gut and listeriosis in a mouse model. Microbial community shift showed a favorable disposition to overcome dysbiotic conditions, and improved gut health and overall well-being. Bioengineered feeding ameliorated gut inflammation, thus offering a potential dietary supplement for reducing gut-associated inflammation and enhancing gut health in livestock.