The role of zinc in shaping host- microbe interactions in the gutdissertationsGordon, SarahcreatorVaishnava, ShipraAdvisorBartnikas, TomAdvisorDawson, MichelleAdvisorWharton, KristiAdvisorBel, ShaiReaderBrown University. Department of Molecular Biology, Cell Biology and Biochemistrysponsor2022, None p.born digitalThesis (Ph. D.)--Brown University, 2022thesesAdherent bacteria are members of the resident gut microbiota that can bypass host-imposed immune responses to directly attach to the intestinal epithelium. While adherent bacteria are found within the gut of healthy individuals, their colonization and expansion within the ileal mucosal microbiota exacerbates local and extra-intestinal inflammation underlying various autoimmune diseases, such as Crohn’s Disease, Rheumatoid Arthritis, and Multiple Sclerosis. Here, zinc supplementation was tested on two adherent microbes, Segmented Filamentous Bacteria (SFB) and a strain of Adherent- Invasive E coli (AIEC) isolated from the ileal mucosa from a patient with Crohn’s Disease. Zinc therapy depleted SFB from the murine mucosal microbiota, thereby dampening intestinal T-helper 17 (Th17) cell induction in vivo. Th17 cells induced by SFB, which are involved in maintaining barrier function and protecting against enteropathogens, were also shown to become autoreactive and contribute to disease pathology in susceptible hosts. Fecal microbiota transfer (FMT) from zinc treated mice into germ-free mice recaptured the reduced Th17 cell phenotype. Additionally, zinc therapy cleared AIEC from the murine ileal mucosa in a pre-clinical model of AIEC colonization. This work provides a novel nutritional approach to dampen inflammatory potential of the gut microbiota through targeted elimination of adherent bacteria from the ileal mucosa.gut microbiomeZinc--Physiological effectmucosal immunityTh17 cellsEnglishRPB20221018