Intestinal dysbiosis as an intraoperative predictor of septic complications: evidence from human surgical cohorts and preclinical models of peritoneal sepsis

Abstract

Abstract Major surgery exposes the intestinal microbiota to inflammatory and antibiotic stressors, which alter the microbiota composition of the intestinal lumen and fecal contents. However, it is not sufficiently understood, if such dysbiosis develops already during surgery and if alterations in microbiota may be the cause of surgical complications. End-of-surgery composition of the microbiota in the rectum was assessed in 41 patients undergoing either rectal or duodenopancreatic resection and was compared to baseline before surgery using 16S-rRNA sequencing. A subset of patients developed severe dysbiosis at the end of surgery, which was characterized by an overgrowth of the Proteobacteria phylum that includes the facultative pathogen E. coli. To test if dysbiosis impacts on surgical outcomes, dysbiosis was modeled in mice by a single oral administration of vancomycin prior to cecal ligation and puncture. Dysbiosis was associated with impaired post-surgical survival, dysregulation of the host’s immune response, elevated bacterial virulence and reduced bacterial metabolism of carbon sources. In conclusion, dysbiosis can be detected already at the end of surgery in a fraction of patients undergoing major surgery. Modelling surgery-associated dysbiosis in mice using single-shot administration of vancomycin induced dysbiosis and resulted in elevated mortality.