title: Administration of defined microbiota is protective in a murine Salmonella infection model.
abstract: Salmonella typhimurium is a major cause of diarrhea and causes significant morbidity and mortality worldwide, and perturbations of the gut microbiota are known to increase susceptibility to enteric infections. The purpose of this study was to investigate whether a Microbial Ecosystem Therapeutic (MET-1) consisting of 33 bacterial strains, isolated from human stool and previously used to cure patients with recurrent Clostridium difficile infection, could also protect against S. typhimurium disease. C57BL/6 mice were pretreated with streptomycin prior to receiving MET-1 or control, then gavaged with S. typhimurium. Weight loss, serum cytokine levels, and S. typhimurium splenic translocation were measured. NF-κB nuclear staining, neutrophil accumulation, and localization of tight junction proteins (claudin-1, ZO-1) were visualized by immunofluorescence. Infected mice receiving MET-1 lost less weight, had reduced serum cytokines, reduced NF-κB nuclear staining, and decreased neutrophil infiltration in the cecum. MET-1 also preserved cecum tight junction protein expression, and reduced S. typhimurium translocation to the spleen. Notably, MET-1 did not decrease CFUs of Salmonella in the intestine. MET-1 may attenuate systemic infection by preserving tight junctions, thereby inhibiting S. typhimurium from gaining access to the systemic circulation. We conclude that MET-1 may be protective against enteric infections besides C. difficile infection.
authors.affiliation: Dept. Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: Sarah-Lynn E
authors.initials: SL
authors.lastname: Martz
authors.affiliation: Dept. Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: Julie A K
authors.initials: JA
authors.lastname: McDonald
authors.affiliation: Division of Gastroenterology and Hepatology Department of Medicine University of Illinois at Chicago, Chicago, IL, 60612, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Gastroenterology and Hepatology Department of Medicine University of Illinois at Chicago, Chicago, IL, 60612, USA.
authors.forename: Yong-Guo
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Dept. Biochemistry, University of Western Ontario, London, Ontario, N6A 5C1, Canada.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Gloor
authors.affiliation: Dept. Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Noordhof
authors.affiliation: Dept. Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: He
authors.affiliation: Dept. Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: Teklu K
authors.initials: TK
authors.lastname: Gerbaba
authors.affiliation: Dept. Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Blennerhassett
authors.affiliation: Dept. Pathology &Molecular Medicine, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hurlbut
authors.affiliation: Dept. Molecular &Cellular Biology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: Allen-Vercoe
authors.affiliation: Depts. Pediatrics and Medicine, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Claud
authors.affiliation: Dept. Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada.
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Petrof
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D001835:Body Weight; D002432:Cecum / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism; D003092:Colitis / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D009077:Mucins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D012486:Salmonella typhimurium / Q000254:growth & development / Q000472:pathogenicity; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000382:microbiology; D019108:Tight Junctions / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062445:Claudin-1; D016207:Cytokines; D009077:Mucins; D016328:NF-kappa B; D012336:RNA, Ribosomal, 16S; C569043:Tjp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein