Project: Nutrition and aryl hydrocarbon receptor activation in mesenteric adipose tissue inflammation and intestinal surgical site infections in metabolic syndrome
| Acronym | METARYL |
| Project Topic | The world-wide burden of metabolic syndrome (obesity and related illnesses such as type 2 diabetes mellitus) is a high source of infectious complications. Moreover, it worsens the course and prognosis of infections, leading to higher mortality rates. A better understanding of mechanisms underlying the association between obesity and infections, and the identification of more effective treatment strategies is urgently needed. Surgical site infections (SSI) are frequent and potentially life-threatening complications (8-15%) in patients undergoing colorectal surgery, with high morbidity and short-term mortality rate (39%). Metabolic syndrome is a significant risk factor for post-operative intestinal infections, particularly in rectal anastomoses, yet the mechanisms underlying this relationship remain unclear. Tryptophan (Trp) is an essential amino acid derived from dietary intake of protein-rich food [8]. It can be metabolized by microbial communities into indole derivatives that can act as agonists of the aryl hydrocarbon receptor (AhR). Activation of the AhR has been shown to play a central role in intestinal epithelial homeostasis. Recent studies have shown a decreased production of AhR-agonists by the gut microbiota in the context of metabolic disease. Restoring AhR signalling in murine obese models induced beneficial effects on metabolic syndrome, including restoration of gut barrier defect and secretion of GLP-1. Notably, the relationship between obesity/T2D and microbiome-derived AhR-activation in intestinal anastomosis healing (AH) and surgical site intestinal infections (peritonitis, sepsis, and death) is poorly understood. Our proposal aims to investigate how diet related tryptophan metabolites (produced by the gut microbiota) affect patients with metabolic syndrome to develop a intestinal surgical site infections (SSI). |
| Network | JPI HDHL |
| Call | NUTRIMMUNE |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Amsterdam university medical center | Coordinator | Netherlands |
| 2 | Institut national de la santé et de la recherche médicale | Partner | France |
| 3 | Universitätsklinikum Bonn | Partner | Germany |
| 4 | Johanniter-Kliniken Bonn | Partner | Germany |
| 5 | Amsterdam university medical center | Partner | Netherlands |
| 6 | Amsterdam university medical center | Observer | Netherlands |
| 7 | Amsterdam university medical center | Observer | Netherlands |