Iron Sequestration in Microbiota Biofilms in Treatment for IBD

Host: Damian Maseda, D.M.Sc., PhD
Iron Sequestration in Microbiota Biofilms As A Novel Strategy for Treating Inflammatory Bowel Disease. Jean-Paul Motta, PhD Thibault Allain, PhD Luke E Green-Harrison, BScRyan A Groves, MSc Troy Feener, MSc Hena Ramay, PhD Paul L Beck, MD/PhDIan A Lewis, PhD John L Wallace, PhD Andre G Buret, PhD ABSTRACT: Significant alterations of intestinal microbiota and anemia are hallmarks of inflammatory bowel disease (IBD). It is widely accepted that iron is a key nutrient for pathogenic bacteria, but little is known about its impact on microbiota associated with IBD. We used a model device to grow human mucosa-associated microbiota in its physiological anaerobic biofilm phenotype. Compared to microbiota from healthy donors, microbiota from IBD patients generate biofilms ex vivo that were larger in size and cell numbers, contained higher intracellular iron concentrations, and exhibited heightened virulence in a model of human intestinal epithelia in vitro and in the nematode Caenorhabditis elegans. We also describe an unexpected iron-scavenging property for an experimental hydrogen sulfide-releasing derivative of mesalamine. The findings demonstrate that this new drug reduces the virulence of IBD microbiota biofilms through a direct reduction of microbial iron intake and without affecting bacteria survival or species composition within the microbiota. Metabolomic analyses …