Gut microbes of the cecum versus the colon drive more severe lethality and multi-organ damage.

Summary

In a murine fecal-induced peritonitis model, cecal intestinal contents caused more lethal sepsis than colonic contents, with shorter median survival, higher multi-organ damage, and stronger systemic inflammation. Mechanistically, cecal contents carried higher bacterial burden, distinct microbial communities enriched for pathogens, and induced stronger cGAS-STING and TBK1-NF-κB signaling.

Key Findings

• Cecum-derived intestinal contents caused shorter median survival and greater multi-organ damage than colon-derived contents in mice.
• Cecal contents exhibited higher bacterial burden and a distinct microbiome enriched with potentially pathogenic taxa.
• Cecal contents triggered stronger activation of cGAS-STING and TBK1-NF-κB signaling with elevated systemic cytokines and lung inflammation.

Clinical Implications

Perforation site (cecum vs colon) may inform early risk stratification, source control urgency, and empiric antimicrobial breadth. However, clinical translation requires human validation.

Limitations

• Preclinical mouse model with peritoneal injection may not fully recapitulate human perforation physiology
• Exact sample sizes and power calculations were not specified in the abstract

Future Directions

Validate findings in clinical cohorts of right- versus left-sided perforations, and dissect microbial taxa and host pathways (cGAS-STING/TBK1-NF-κB) amenable to targeted interventions.