title: Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model.
abstract: Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if this candidate probiotic could reduce bone loss associated with estrogen deficiency in an ovariectomized (Ovx) mouse menopausal model. Strikingly, L. reuteri treatment significantly protected Ovx mice from bone loss. Osteoclast bone resorption markers and activators (Trap5 and RANKL) as well as osteoclastogenesis are significantly decreased in L. reuteri-treated mice. Consistent with this, L. reuteri suppressed Ovx-induced increases in bone marrow CD4+ T-lymphocytes (which promote osteoclastogenesis) and directly suppressed osteoclastogenesis in vitro. We also identified that L. reuteri treatment modifies microbial communities in the Ovx mouse gut. Together, our studies demonstrate that L. reuteri treatment suppresses bone resorption and loss associated with estrogen deficiency. Thus, L. reuteri treatment may be a straightforward and cost-effective approach to reduce post-menopausal bone loss.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, 48824.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Britton
authors.forename: Regina
authors.initials: R
authors.lastname: Irwin
authors.forename: Darin
authors.initials: D
authors.lastname: Quach
authors.forename: Laura
authors.initials: L
authors.lastname: Schaefer
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Taehyung
authors.initials: T
authors.lastname: Lee
authors.forename: Narayanan
authors.initials: N
authors.lastname: Parameswaran
authors.forename: Laura R
authors.initials: LR
authors.lastname: McCabe
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy* / Q000517:prevention & control*; D002454:Cell Differentiation; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000473:pathology; D005434:Flow Cytometry; D007778:Lactobacillus; D008593:Menopause; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy; D025341:Principal Component Analysis; D019936:Probiotics / Q000627:therapeutic use*; D053245:RANK Ligand / Q000378:metabolism; D013131:Spine / Q000473:pathology
chemical_list: D015415:Biomarkers; D053245:RANK Ligand