Targeted screening of an anti-inflammatory polypeptide from Rhopilema esculentum Kishinouye cnidoblasts and elucidation of its mechanism in alleviating ulcerative colitis based on an analysis of the gut microbiota and metabolites

Abstract

Ulcerative colitis (UC) is a recurrent inflammatory bowel disease that imposes a severe burden on families and society. In recent years, exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest. This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV (Pro-Lys-Lys-Val-Val) of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome. Specif ically, the polypeptide composition of R. esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α (TNF-α) than the original ligand. Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC; affect serum metabolites through the arachidonic acid, glycerophospholipid and linoleic acid metabolism pathways; and further alleviate UC symptoms. This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.

Keywords

• ulcerative colitis
• rhopilema esculentum kishinouye
• cnidoblasts
• marine bioactive polypeptides
• metagenome
• serum metabolome