title: Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties.
abstract: Alterations in the gut microbiome have been associated with changes in bone mass and microstructure, but the effects of the microbiome on bone biomechanical properties are not known. Here we examined bone strength under two conditions of altered microbiota: (1) an inbred mouse strain known to develop an altered gut microbiome due to deficits in the immune system (the Toll-like receptor 5-deficient mouse [TLR5KO]); and (2) disruption of the gut microbiota (ΔMicrobiota) through chronic treatment with selected antibiotics (ampicillin and neomycin). The bone phenotypes of TLR5KO and WT (C57Bl/6) mice were examined after disruption of the microbiota from 4 weeks to 16 weeks of age as well as without treatment (n = 7 to 16/group, 39 animals total). Femur bending strength was less in ΔMicrobiota mice than in untreated animals and the reduction in strength was not fully explained by differences in bone cross-sectional geometry, implicating impaired bone tissue material properties. Small differences in whole-bone bending strength were observed between WT and TLR5KO mice after accounting for differences in bone morphology. No differences in trabecular bone volume fraction were associated with genotype or disruption of gut microbiota. Treatment altered the gut microbiota by depleting organisms from the phyla Bacteroidetes and enriching for Proteobacteria, as determined from sequencing of fecal 16S rRNA genes. Differences in splenic immune cell populations were also observed; B and T cell populations were depleted in TLR5KO mice and in ΔMicrobiota mice (p < 0.001), suggesting an association between alterations in bone tissue material properties and immune cell populations. We conclude that alterations in the gut microbiota for extended periods during growth may lead to impaired whole-bone mechanical properties in ways that are not explained by bone geometry. © 2017 American Society for Bone and Mineral Research.
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Guss
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Horsfield
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Fernanda F
authors.initials: FF
authors.lastname: Fontenele
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Taylor N
authors.initials: TN
authors.lastname: Sandoval
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Marysol
authors.initials: M
authors.lastname: Luna
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Fnu
authors.initials: F
authors.lastname: Apoorva
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: Svetlana F
authors.initials: SF
authors.lastname: Lima
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: Rodrigo C
authors.initials: RC
authors.lastname: Bicalho
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Ankur
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, NY, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.|Hospital for Special Surgery, New York, NY, USA.
authors.forename: Marjolein Ch
authors.initials: MC
authors.lastname: van der Meulen
authors.affiliation: Hospital for Special Surgery, New York, NY, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldring
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.|Hospital for Special Surgery, New York, NY, USA.
authors.forename: Christopher J
authors.identifier: http://orcid.org/0000-0002-0712-6533
authors.initials: CJ
authors.lastname: Hernandez
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000502:physiology*; D000069196:Gastrointestinal Microbiome; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D051198:Toll-Like Receptor 5 / Q000378:metabolism
chemical_list: D051198:Toll-Like Receptor 5
keywords: BIOMECHANICS; BONE MATRIX; OSTEOIMMUNOLOGY; OSTEOPOROSIS