Colon microenvironment restorative nano-armored probiotics–rosmarinic acid bioconjugation for synergistic alleviation of inflammatory bowel disease

Abstract

Oral probiotics and polyphenols are increasingly recognized as effective treatments for inflammatory bowel disease (IBD). However, their practical application is hindered by the acidic gastric environment and digestive enzymes. Herein, we propose a strategy employing pH-responsive materials to co-deliver probiotics and polyphenol drugs for the synergistic alleviation of IBD. Through bioconjugation, Escherichia coli Nissle 1917 (EcN) was linked with rosmarinic acid (RA). Introducing calcium ions (Ca²⁺) that accumulated on the probiotic surface facilitated the formation of a pH-responsive enteric coating. This coating, composed of hydroxypropyl methylcellulose acetate succinate (HPMCAS) mixed with sodium alginate (SA), acted as a protective nano-armor on the surface, yielding EcN-RA@AS/SA. This nano-armor protected the probiotics during gastric transit, ensuring their safe delivery to the intestine. In a mouse model of IBD, EcN-RA@AS/SA demonstrated efficacy in restoring the colon microenvironment by alleviating symptoms through downregulating the expression of proinflammatory cytokines, repairing the intestinal barrier, and regulating the gut flora.