Background: Sepsis is a critical condition characterized by organ failure due to the body's inappropriate reaction to an infection. The disrupted gut microbiome is constantly changing and contributes to the development of sepsis. This research seeks to explore the makeup and role of gut microbiota in individuals experiencing sepsis or septic shock and the sepsis rat model induced by cecal ligation and puncture (CLP).

Methods: Fecal samples from persons in the healthy control group, sepsis, and septic shock patients were collected. The intestinal flora was examined using 16S rRNA-sequencing analysis. Besides, SD rats were subjected to CLP surgery to create a sepsis model. Post-surgery, mice were euthanized at 6, 12, 24, and 48 h to evaluate inflammatory mediators, intestinal microbiota, morphology, and intestinal barrier markers.

Results: In patients and rats with sepsis, the intestinal barrier was notably disrupted, intestinal permeability was significantly increased, and the inflammatory level was conspicuously elevated (p < 0.05). In sepsis patients and CLP-induced rats, the variety and balance of gut microbiota were reduced. Compared with the control group, sepsis patients had lower abundances of Agathobacter, Coprococcus, Erysipelotrichaceae_UCG-003, Faecalibacterium, Fusicatenibacter, Haemophilus, Roseburia and Subdoligranulum, but increased abundances of Corynebacterium and Enterococcus compared to the control group. CLP rats exhibited more severe cortical inflammation and enhanced intestinal permeability. The higher Bacillus, Sutterella, Odoribacter, Pseudomonas, Brochothrix, Clostridium, Enterococcus, and Ruminococcus abundances at the genus level were shown in CLP surgery after 6, 12, 24, and 48 h. KEGG analysis revealed a significant enrichment in carbohydrate metabolism, cofactors and vitamins metabolism, terpenoid and polyketide metabolism, as well as amino acid metabolism.

Conclusion: Taken together, beneficial bacteria like Agathobacter, Coprococcus, Erysipelotrichaceae_UCG-003, and Faecalibacterium decline, while harmful species such as Corynebacterium and Enterococcus increase, which might contribute to triggering intense inflammation and compromising intestinal barrier function in the progression of sepsis. These shifts highlight potential microbial targets for sepsis treatment.