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

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 effects in vitro by reducing proinflammatory mediator secretion and inhibiting NF-κB signaling in immune cells. Ex vivo human intestinal model confirmed its ability to promote mucosal healing, while in vivo studies 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.