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.

The Combined Effect of Western Diet Consumption and Diclofenac Administration Alters the Gut Microbiota and Promotes Anastomotic Leakage in the Distal Colon.

Background: Obesity, Western diet (WD) consumption, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are co-occurring and modifiable factors associated with microbiome dysbiosis and anastomotic leakage. We studied the combined effect of a Western-type diet (WD) and diclofenac, a standard NSAID used in surgical patients, on anastomotic healing and gut microbiota composition following distal colon resection.

Methods: Forty-two rats were fed a WD for 6 weeks, after which they were randomized to either parenteral diclofenac 3 mg/kg/day or saline started on the day of surgery and continued for three days.

Peptide YY: A Paneth cell antimicrobial peptide that maintains gut commensalism.

The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility whereas others regulate the microbiota. We have found that peptide YY (PYY), but not endocrine PYY, acts as an antimicrobial peptide (AMP) expressed by gut epithelial paneth cells (PC). PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity.

Western Diet-induced Transcriptional Changes in Anastomotic Tissue Is Associated With Early Local Recurrence in a Mouse Model of Colorectal Surgery.

Objective: To determine the timeframe and associated changes in the microenvironment that promote the development of a diet-induced local-regional recurrence in a mouse model of colorectal surgery.

Background: Postoperative recurrence and metastasis occur in up to 30% of patients undergoing attempted resection for colorectal cancer (CRC). The underlying mechanisms that drive the development of postoperative recurrences are poorly understood.

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.