title: Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.
abstract: The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Carli J
authors.initials: CJ
authors.lastname: Smith
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Jacob R
authors.initials: JR
authors.lastname: Emge
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Katrina
authors.initials: K
authors.lastname: Berzins
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Lydia
authors.initials: L
authors.lastname: Lung
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Khamishon
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Paarth
authors.initials: P
authors.lastname: Shah
authors.affiliation: Cell Biology Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Rodrigues
authors.affiliation: Cell Biology Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sousa
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Colin
authors.initials: C
authors.lastname: Reardon
authors.affiliation: Cell Biology Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sherman
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Barrett
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; and mgareau@ucdavis.edu.
authors.forename: Mélanie G
authors.initials: MG
authors.lastname: Gareau
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001007:Anxiety / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D019936:Probiotics / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology
chemical_list: D018398:Homeodomain Proteins; D016760:Proto-Oncogene Proteins c-fos; C064658:RAG-1 protein
keywords: anxiety; behavior; memory; microbiota; probiotics; stress