Final Report, ECCO Grant for Shai Bel

Shai Bel, ECCO Grant Awardee

The role of autophagy in limiting IBD-associated AIEC-induced intestinal inflammation

Shai Bel
© Shai Bel

Background & aim of research

While the aetiology underlying the development of Inflammatory Bowel Diseases (IBD) is unclear, evidence points to an interaction between host genetics, such as mutations in autophagy genes, and environmental factors, such as bacterial infections. Multiple studies have identified an adherent-invasive Escherichia coli pathotype (AIEC) only in patients with IBD. It is thought that AIEC exploits the intestinal inflammation in patients with IBD to attach to intestinal epithelial cells, intensifying the pre-existing inflammation. Studies in vitro have shown that functional autophagy is crucial to eliminate AIEC infection. Here, we aimed to identify how autophagy protects the host from AIEC-associated pathologies in vivo.

Methodology used in the research

Genetically engineered Becn1F121A mice, in which the autophagy process is constitutively active, were infected with an AIEC strain and disease progression was monitored.

Main findings/results of the research

We found that Becn1F121A mice were protected from acute and chronic infection with AIEC and from the subsequent intestinal inflammation. This protection was the result of a thicker colonic mucus layer in Becn1F121A mice.

Conclusions and perceived impact of the findings

We conclude that autophagy is crucial for protection from AIEC colonisation via regulation of the colonic mucus layer. These results suggest that impairment of autophagy in patients carrying mutations in autophagy genes might predispose to AIEC colonisation and inflammation.

Plan of publication

These results have been published: DOI: 10.1016/j.chom.2023.01.006.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 3, Fellowships & Grants Synopsis Reports