Development of a combination of probiotics and plant extracts targeting adherent-invasive Escherichia coli associated with Crohn's disease.

Abnormal colonisation of the ileal mucosa by adherent-invasive Escherichia coli (AIEC) is a key feature of Crohn's disease. To date, no curative treatment for this disease exists, highlighting the need to develop new therapies targeting the origin of the inflammation, in particular the intestinal microbiota and more specifically AIEC. This study investigated the anti-virulence properties of 17 bacterial strains (lactobacilli and bifidobacteria) and three plant extracts (walnut and green tea leaves and liquorice roots) against AIEC. In vitro, six lactobacilli strains and one bifidobacterium strain reduced AIEC LF82 adhesion to Caco-2/TC7 cells and/or suppressed IL-8 secretion induced by AIEC. Although plant extracts did not prevent adhesion or inflammation, they inhibited AIEC growth. In a murine model of dextran sulfate sodium-induced colitis exacerbated by LF82 infection, two Lacticaseibacillus strains, one Bifidobacterium strain, and walnut and green tea extracts efficiently alleviated colitis and reduced faecal lipocalin-2 levels. For the green tea extract and one Lacticaseibacillus strain, beneficial effects were correlated with a decreased number of AIEC associated with the colonic mucosa. Building on these findings, bacteria and plant extract combinations were tested in the same model. A formulation combining two Lacticaseibacillus strains (Lbs. casei and Lbs. rhamnosus) with the walnut extract demonstrated the greatest efficacy, markedly reducing colitis score and preserving intestinal mucosa integrity. While untreated mice remained heavily colonised, the combination promoted AIEC elimination from the gut of half the mice, contributing to the alleviation of colitis symptoms. These results highlight the ability of combinations of specific bacteria/plant extracts to limit the presence of AIEC in the ileal mucosa of Crohn's disease patients, presenting a promising approach for disease management.