Article: Guss, JD; Horsfield, MW; Fontenele, FF; Sandoval, TN; Luna, M; Apoorva, F; Lima, SF; Bicalho, RC; Singh, A; Ley, RE; van der Meulen, MCH; Goldring, SR; Hernandez, CJ; “Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties”, Journal of Bone and Mineral Research, 32 (6):1343-1353
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 (Delta Microbiota) 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 DMicrobiota 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 DMicrobiota 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. (C) 2017 American Society for Bone and Mineral Research.
Funding Acknowledgement: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (U.S) [AR068061]; Office of the Assistant Secretary of Defense for Health Affairs through the office of the Congressionally Directed Medical Research Programs (CDMRP) [W81XWH-15-1-0239]
Funding Text: This work was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (U.S) under Award Number AR068061 and by the Office of the Assistant Secretary of Defense for Health Affairs through the office of the Congressionally Directed Medical Research Programs (CDMRP) under Award No. W81XWH-15-1-0239. The content of the work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense. We thank Adrian Alepuz for his help in analyzing mechanical testing data.