Klebsiella enrichment is associated with disease severity in ulcerative colitis

Ulcerative colitis (UC), a chronic inflammatory bowel disease. This study uniquely undertook a parallel, severity-stratified comparison of both fecal and mucosal microbiota and metabolites in UC patients. Our objective was to identify niche-specific (fecal vs. mucosal) and severity-associated microbial and metabolic signatures, clarifying its potential clinical utility.

A prospective cohort study (ChiCTR2300071816) enrolled 83 UC patients (≥18 years) from the First Affiliated Hospital of Nanjing Medical University and Northern Jiangsu People's Hospital (Jan 2022-Dec 2024) and 30 healthy controls. Clinical data, stool, and rectal mucosal samples were collected. Metagenomic sequencing and metabolomics were performed. Disease severity was stratified by modified Mayo score to analyze microbiota diversity, differential genera, metabolites, and enriched metabolic pathways.

Fecal microbiota α-diversity was significantly lower in UC vs. controls (Shannon index 4.15 vs. 5.44, P = 0.005); mucosal diversity showed no difference (P = 0.63). Beta diversity did not differ. Severe UC exhibited a non-significant decrease in α-diversity (fecal: 3.99 vs. 4.37, P = 0.14; mucosal: 3.40 vs. 3.72, P = 0.92), significantly higher fecal/mucosal Klebsiella abundance, and lower Erysipelatoclostridium and Blautia abundance vs. mild-to-moderate UC. Metabolomics identified 363 fecal differential metabolites (e.g. allopurinol, histidine), enriching tyrosine, and alanine/aspartate/glutamate metabolism pathways. Mucosal analysis revealed 127 differential metabolites (e.g. quinic acid, sphingosine), implicating sphingolipid metabolism and lysine synthesis.

UC demonstrates gut dysbiosis and metabolic disruption correlating with severity. Elevated Klebsiella abundance suggests a pathogenic role in progression. Distinct fecal and mucosal metabolic pathway alterations provide novel insights for disease classification and therapeutic targeting.