EB1010, a putative Christensenellaceae-derived microbial peptide, exhibits anti-inflammatory activity and therapeutic potential in ulcerative colitis.

Abstract

The gut microbiota plays a pivotal role in modulating the immune system, fostering immune tolerance, and defending against pathogens. Among its bioactive products, microbiota-derived peptides hold therapeutic promise for inflammatory diseases. In this study, we present EB1010, a 28-residue peptide derived from an unknown protein of a Christensenellaceae bacterium, as potential treatment of ulcerative colitis (UC). EB1010 exhibit strong anti-inflammatory effectsby reducing proinflammatory mediator secretion and inhibiting NF-κB signaling in immune cells.human intestinal model confirmed its ability to promote mucosal healing, whilestudies demonstrated that oral administration effectively reversed inflammation in both trinitrobenzene sulfonic acid- (TNBS)-induced rat and DSS-induced mouse models of colitis. Caco-2 transport assays revealed minimal peptide permeability, consistent with pharmacokinetic (PK) data showing no plasma detection in orally treated rats, supporting a local intestinal mode of action. EB1010 was well tolerated in a 4-week rat toxicology study, with no adverse effect observed at doses up to 1.5 mg/kg/d by intravenous administration. These findings position EB1010 as a safe, locally acting, microbiota-derived peptide with potential therapeutic applications.