Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction

Pathobionts employ unique metabolic adaptation mechanisms to maximize their growth in disease condi-tions. Adherent-invasive Escherichia coli (AIEC), a pathobiont enriched in the gut mucosa of patients with inflammatory bowel disease (IBD), utilizes diet-derived L-serine to adapt to the inflamed gut. Therefore, the restriction of dietary L-serine starves AIEC and limits its fitness advantage. Here, we find that AIEC can overcome this nutrient limitation by switching the nutrient source from the diet to the host cells in the pres-ence of mucolytic bacteria. During diet-derived L-serine restriction, the mucolytic symbiont Akkermansia muciniphila promotes the encroachment of AIEC to the epithelial niche by degrading the mucus layer. In the epithelial niche, AIEC acquires L-serine from the colonic epithelium and thus proliferates. Our work sug-gests that the indirect metabolic network between pathobionts and commensal symbionts enables patho-bionts to overcome nutritional restriction and thrive in the gut.

Automated summary

Pathobiont AIEC can overcome dietary L-serine restriction and adapt to the gut by switching nutrient sources with the help of mucolytic bacteria, promoting the encroachment to the epithelial niche and acquiring L-serine from the colonic epithelium for proliferation.