Title Information
Title
The role of zinc in shaping host- microbe interactions in the gut
Type of Resource (primo)
dissertations
Name: Personal
Name Part
Gordon, Sarah
Role
Role Term: Text
creator
Name: Personal
Name Part
Vaishnava, Shipra
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Bartnikas, Tom
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Dawson, Michelle
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Wharton, Kristi
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Bel, Shai
Role
Role Term: Text
Reader
Name: Corporate
Name Part
Brown University. Department of Molecular Biology, Cell Biology and Biochemistry
Role
Role Term: Text
sponsor
Origin Information
Copyright Date
2022
Physical Description
Extent
, None p.
digitalOrigin
born digital
Note: thesis
Thesis (Ph. D.)--Brown University, 2022
Genre (aat)
theses
Abstract
Adherent 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.
Subject
Topic
gut microbiome
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01184397")
Topic
Zinc--Physiological effect
Subject
Topic
mucosal immunity
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/02000599")
Topic
Th17 cells
Language
Language Term (ISO639-2B)
English
Record Information
Record Content Source (marcorg)
RPB
Record Creation Date (encoding="iso8601")
20221018