Microbial Modulation of Inflammation

The group’s primary research focus centers on the adherent-invasive Escherichia coli (AIEC) pathovar, which is found with higher prevalence and increased abundance in the intestinal mucosa of patients with inflammatory bowel disease (IBD), and Crohn’s disease in particular. These strains are notably characterized by their intracellular presence within intestinal epithelial cells and their ability to survive inside macrophages. The mechanisms accounting for this occurrence, as well as the role of AIEC in initiating and/or sustaining inflammation, remain only partially understood. To date, no reliable molecular marker is available, and AIEC identification, which remains primarily phenotypic, is relatively labor-intensive. Because AIEC are sometimes isolated from asymptomatic individuals, our hypothesis is that the occurrence and abundance of this pathovar could serve as a biomarker of dysbiosis or a pre-dysbiotic state in the general population. Indeed, individual and temporal AIEC carriage appears to be associated with an increased susceptibility to infection and a state of "inflammatory fragility", particularly in children, in low-grade chronic inflammatory conditions linked to metabolic disorders, neurological disorders, and aging, as well as in cancer immunotherapy-induced colitis.

In parallel, the functional diversity and pathophysiology of different AIEC clones remain poorly studied and require multifaceted, interdisciplinary in vitro and in vivo approaches—ranging from bacterial genomics (identifying specific sequences, such as the presence of prophages) to the phenotypic characterization of host-pathogen interactions (immunological signatures, inflammatory responses).

While mice remain a model of choice, bacterial colonization can also be modeled using human intestinal organoids derived from Crohn’s disease patient biopsies, or by utilizing non-mammalian invertebrate alternatives (Caenorhabditis elegans nematodes, Galleria mellonella larvae) to compare and characterize the underlying mechanisms.

Beyond their clear value for diagnosis, epidemiology, and monitoring disease progression and treatment response, these tools should help assess the synergistic or antagonistic contributions of other gut microbiota members, as well as test the efficacy of targeted small molecules or probiotics designed for anti-inflammatory and anti-invasive purposes. Indeed, inter-microbial interactions within the gut microbiota are highly likely to act as "contributing" or "facilitating" factors in the invasive mechanisms and pathophysiology of AIEC.

Keywords: Intestinal inflammation, Pathobionts, Symbionts, Adherent-invasive E. coli (AIEC), Prophages, Bacteriophages, Probiotics, Galleria mellonella