Data Sheet 2_Elevated postoperative IL-1β induces disorder of intestinal microenvironment and alteration of gut microbiota.docx

IntroductionPrevious research hinted at the importance of postoperative gut dysbiosis prevention, but the mechanisms remained unclear, posing a challenge for prevention and therapy. This study aims to investigate the characteristics of postoperative dysbiosis and the underlying mechanisms.
MethodsThe clinical cohort investigated the perioperative change of gut microbiota in patients undergoing thoracoscopy and its relationship with peripheral inflammatory indicators. Gut microbiome was characterized by 16S rRNA gene sequencing and Bugbase phenotype analysis. In the laboratory study, a mouse model of surgery/anesthesia stress was established to further investigate the potentially underlying mechanisms.
ResultsMicrobiome analysis revealed a decrease in alpha diversity and a shift from obligate anaerobes to aerobes/facultative anaerobes after thoracoscopy. Postoperative IL-1β was negatively correlated with obligate anaerobe abundance and positively correlated with facultative anaerobe abundance. Higher facultative anaerobe abundance was associated with increased risk of postoperative complications and longer hospital stays. In the mouse model, surgery and rIL-1β intervention mirrored the oxygen phenotype changes in clinical cohort, and the colonic epithelium exhibited decreased ATP levels and hypoxic staining scores, with increased lactic acid. Downregulating postoperative IL-1β with IL-1β siRNA mitigated colonic hypoxic environment impairment and gut microbiota oxygen phenotype changes induced by surgery/anesthesia stress.
ConclusionPostoperative gut dysbiosis involves a phenotypic shift of the gut microbiota from anaerobes toward aerobes and facultative anaerobes. This shift may be driven by an IL-1β–colonic epithelial oxygen metabolism–colonic oxygen environment–gut microbiota regulatory axis, offering potential insights for early risk stratification of severe postoperative complications and strategies to improve postoperative recovery.