Hyaluronic Acid-Nanocoated Bacteria Generate an Anti-Inflammatory Tissue-Repair Effect in Impaired Gut and Extraintestinal Organs

Abstract

Diverse extraintestinal diseases are characterized by localized inflammatory responses and tissue damage, accompanied with intestinal inflammation and injury. Here, a dual-functionality and dual-location intervention strategy is reported, which is the use of hyaluronic acid-nanocoated Clostridium butyricum to generate an anti-inflammatory tissue-repair effect in the impaired gut and extraintestinal organs. Nanocoated bacteria attenuate intestinal mucosal inflammation and recover gut barrier integrity by leveraging the immunosuppressive nature of hyaluronic acid and the butyrate-producing ability of Clostridium butyricum. Nanocoated bacteria also alleviate the interstitial inflammation and pathological damage of extraintestinal organs via remodeling microbial metabolites and decreasing microbial translocation. In murine models of acute kidney injury and chronic kidney disease, oral delivery of nanocoated bacteria demonstrates the potency to restore renal function and eliminate renal fibrosis. This work proposes a type of next-generation living therapeutics for treating extraintestinal diseases.

Keywords: gut microbiome; kidney diseases; living therapeutics; nanocoating; oral delivery.