Gut microbiome-mediated nutrients alter opportunistic bacterial growth in peritonitis.

Peritonitis is a well-known complication of bowel perforation and abdominal surgery, leading to sepsis and high mortality. Despite its prevalence and severity, the pathogenesis of peritonitis remains incompletely understood, limiting our ability to develop targeted medical therapies. Specifically, little is known about the determinants of the peritoneal nutrient environment for pathogens. The gut microbiome is a well-established source of infectious bacteria in peritonitis, but whether it also modulates levels of nutrients that enable and sustain these infections remains unknown. Using multiple murine models of peritonitis (lipopolysaccharide and cecal slurry), multiple methods of microbiome modulation (germ-free mice and antibiotic-treated mice), novel ex vivo modeling of peritonitis, and nuclear magnetic resonance (NMR) metabolomics of the peritoneal microenvironment, we performed a series of experiments to determine how the gut microbiome influences peritoneal metabolite concentration during peritonitis. We found that both lipopolysaccharide and cecal slurry peritonitis caused consistent changes in high-abundance peritoneal metabolites and that many of these changes were blunted or completely abrogated in antibiotic-treated and germ-free mice. Moreover, we found that peritoneal washings from septic, microbiome-depleted animals supported less bacterial growth of common intra-abdominal pathogens compared with washings from septic conventional animals. We identified the peritoneal nutrients consumed by two common pathogens from the