title: The gut microbiota regulates bone mass in mice.
abstract: The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4(+) T cells and CD11b(+) /GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis.
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Klara.Sjogren@medic.gu.se.
authors.forename: Klara
authors.initials: K
authors.lastname: Sjögren
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engdahl
authors.forename: Petra
authors.initials: P
authors.lastname: Henning
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
authors.forename: Valentina
authors.initials: V
authors.lastname: Tremaroli
authors.forename: Marie K
authors.initials: MK
authors.lastname: Lagerquist
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000276:immunology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005786:Gene Expression Regulation; D005856:Germ-Free Life; D006706:Homeostasis; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D018655:Lymphocyte Count; D054892:Metagenome / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000276:immunology / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology; D012701:Serotonin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D002118:Calcium