title: A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.
abstract: Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
authors.affiliation: Luxembourg Centre for Systems Biomedicine, Esch-sur-Alzette 4362, Luxembourg; University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg. Electronic address: mahesh.desai@lih.lu.
authors.forename: Mahesh S
authors.initials: MS
authors.lastname: Desai
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Seekatz
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Koropatkin
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kamada
authors.affiliation: Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Hickey
authors.affiliation: Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg.
authors.forename: Mathis
authors.initials: M
authors.lastname: Wolter
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Pudlo
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Sho
authors.initials: S
authors.lastname: Kitamoto
authors.affiliation: Aix-Marseille Université, UMR 7257, 13288 Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Terrapon
authors.affiliation: Department of Oncology, Luxembourg Institute of Health, Luxembourg 1526, Luxembourg.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Muller
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
authors.affiliation: Aix-Marseille Université, UMR 7257, 13288 Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Henrissat
authors.affiliation: Luxembourg Centre for Systems Biomedicine, Esch-sur-Alzette 4362, Luxembourg.
authors.forename: Paul
authors.initials: P
authors.lastname: Wilmes
authors.affiliation: Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: emartens@umich.edu.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Martens
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000502:physiology; D003092:Colitis / Q000382:microbiology; D003106:Colon / Q000382:microbiology; D004043:Dietary Fiber / Q000008:administration & dosage*; D004198:Disease Susceptibility; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D004926:Escherichia coli; D005260:Female; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D051379:Mice; D055262:Mucin-2 / Q000235:genetics
chemical_list: D004043:Dietary Fiber; C524626:Muc2 protein, mouse; D055262:Mucin-2
keywords: Akkermansia; Citrobacter rodentium; bacteroides; dietary fiber; gylcans; microbiome; microbiota; mucin; mucus layer; polysaccharides