A host anti-amyloidogenic stomach-specific protein inhibits colonization and biofilm formation by adherent invasive Escherichia coli in the colon

Abstract Gastrokine-1 (Gkn1) is an anti-amyloidogenic host protein secreted into the gut lumen by the stomach. Gut bacteria make functional amyloids to facilitate biofilm formation and biofilms in the gastrointestinal tract are associated with a variety of disorders, including inflammatory bowel disease. Adherent invasive Escherichia coli (AIEC) is a pathobiont that produces amyloids, forms biofilms, and is associated with inflammatory bowel disease. We therefore investigated whether Gkn1 is required to clear AIEC from the gastrointestinal tract by comparing the course of infection in wild-type and Gkn1-deficient (Gkn1 −/− ) mice. Our findings reveal that Gkn1 does not impact initial colonization by AIEC, but is required for effective clearance of AIEC from the distal GI tract. We also find that Gkn1 inhibits biofilm formation by AIEC and that Gkn1 inhibits the formation of amyloid fibers by the functional E. coli amyloid curli. Furthermore, biofilms of AIEC were evident in the distal gut of Gkn1 −/− mice. Together these results indicate that Gkn1 inhibits bacterial amyloid fiber formation, bacterial biofilms, and facilitates clearance of a biofilm forming, IBD-associated, pathobiont from the distal gut. In addition, as the stomach is the sole source of Gkn1, these results implicate the stomach as a source of protection from intestinal biofilms.