Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.

Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis.

A Novel Nonantibiotic Gut-directed Strategy to Prevent Surgical Site Infections.

Objective: To determine the efficacy of an orally delivered phosphate-rich polymer, Pi-PEG, to prevent surgical site infection (SSI) in a mouse model of spontaneous wound infection involving gut-derived pathogens.

Background: Evidence suggests that pathogens originating from the gut microbiota can cause postoperative infection via a process by which they silently travel inside an immune cell and contaminate a remote operative site (Trojan Horse Hypothesis). Here, we hypothesize that Pi-PEG can prevent SSIs in a novel model of postoperative SSIs in mice.

Defining Microbiome Readiness for Surgery: Dietary Prehabilitation and Stool Biomarkers as Predictive Tools to Improve Outcome.

Objectives: Determine whether preoperative dietary prehabilitation with a low-fat, high-fiber diet reverses the impact of Western diet (WD) on the intestinal microbiota and improves postoperative survival.

Background: We have previously demonstrated that WD fed mice subjected to an otherwise recoverable surgical injury (30% hepatectomy), antibiotics, and a short period of starvation demonstrate reduced survival (29%) compared to mice fed a low-fat, high-fiber standard chow (SD) (100%).

Methods: Mice were subjected to 6 weeks of a WD and underwent dietary pre-habilitation (3 days vs 7 days) with a SD prior to exposure to antibiotics, starvation, and surgery.

Spatial Compartmentalization of the Microbiome between the Lumen and Crypts Is Lost in the Murine Cecum following the Process of Surgery, Including Overnight Fasting and Exposure to Antibiotics.

The cecum is a unique region in the mammalian intestinal tract in which the microbiome is localized to two compartments, the lumen and the crypts. The microbiome within crypts is particularly important as it is in direct contact with lining epithelial cells including stem cells. Here, we analyzed the microbiome in cecum of mice using multiple techniques including metagenomics.

Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3.