title: The Bactericidal Lectin RegIIIβ Prolongs Gut Colonization and Enteropathy in the Streptomycin Mouse Model for Salmonella Diarrhea.
abstract: The bactericidal lectin RegIIIβ is inducibly produced by intestinal epithelial cells as a defense against infection by enteropathogens. In the gut lumen, RegIIIβ kills not only certain enteropathogens, but also some commensal bacteria; thus, RegIIIβ is also thought to be an innate immune effector shaping microbiota composition and establishing intestinal homeostasis. Using the streptomycin mouse model for Salmonella colitis, we show that RegIIIβ can promote sustained gut colonization of Salmonella Typhimurium and prolong enteropathy. RegIIIβ expression was associated with suppression of Bacteroides spp. in the gut lumen, prolonged disease-associated alterations in colonic metabolism, and reduced luminal vitamin B6 levels. Supplementation with Bacteroides spp. or vitamin B6 accelerated pathogen clearance from the gut and remission of enteropathy. Our findings indicate that interventions at the level of RegIIIβ and supplementation with Bacteroides spp. or vitamin B6 might open new avenues for therapeutic intervention in the context of Salmonella colitis.
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641 Tokyo, Japan. Electronic address: mikit@pharm.kitasato-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641 Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Goto
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641 Tokyo, Japan.
authors.forename: Mayuka
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641 Tokyo, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okada
authors.affiliation: The Institute of Microbiology, Department of Biology, ETH Zürich, Vladimir-Prelog Weg 4, 8093 Zurich, Switzerland.
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001439:Bacteroides / Q000254:growth & development; D003092:Colitis / Q000188:drug therapy* / Q000382:microbiology; D003106:Colon / Q000382:microbiology; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome; D037102:Lectins / Q000494:pharmacology*; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019936:Probiotics / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology; D019779:Salmonella enterica / Q000187:drug effects / Q000254:growth & development; D013307:Streptomycin; D025101:Vitamin B 6 / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D037102:Lectins; D011994:Recombinant Proteins; D025101:Vitamin B 6; D013307:Streptomycin
keywords: Bacteroides spp.; RegIIIβ; Salmonella diarrhea; enteropathy; gut colonization; vitamin B6