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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #363659

Research Project: Nutrients, Aging, and Musculoskeletal Function

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: The microbial metagenome and bone tissue composition in mice with microbiome-induced reductions in bone strength

Author
item GUSS, JASON - Cornell University - New York
item TAYLOR, ERIK - Cornell University - New York
item ROUSE, ZACH - Cornell University - New York
item ROUBERT, SEBASTIAN - Cornell University - New York
item HIGGINS, CATHERINE - Cornell University - New York
item THOMAS, CORINNE - Rensselaer Polytechnic Institute
item BAKER, SHEFFORD - Cornell University - New York
item VAN DER MEULEN, MARJORLEIN - Cornell University - New York
item VASHISHTH, DEEPAK - Rensselaer Polytechnic Institute
item DONNELLY, EVE - Cornell University - New York
item SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BICALHO, RODRIGO - Cornell University - New York
item HERNANDEZ, CHRISTOPHER - Cornell University - New York

Submitted to: Bone
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/13/2019
Publication Date: 6/14/2019
Citation: Guss, J.D., Taylor, E., Rouse, Z., Roubert, S., Higgins, C.H., Thomas, C.J., Baker, S.P., Van Der Meulen, M.C., Vashishth, D., Donnelly, E., Shea, K., Booth, S.L., Bicalho, R.C., Hernandez, C.J. 2019. The microbial metagenome and bone tissue composition in mice with microbiome-induced reductions in bone strength. Bone. 127:146-154. https://doi.org/10.1016/j.bone.2019.06.010.
DOI: https://doi.org/10.1016/j.bone.2019.06.010

Interpretive Summary: The genetic components of microbial species that inhabit the body are known collectively as the microbiome. Modifications to the microbiome have been implicated in disease processes throughout the body and have recently been shown to influence bone. Prior work has associated changes in gut bacteria with characteristics of bone but has provided limited information regarding mechanisms. With the goal of achieving a more mechanistic understanding of the effects of the microbiome on bone, we performed an analysis of the gut microbiome that provides information on the functional capacity of the microbes. The gut microbiota of one group of male mice were disrupted using oral antibiotics whereas the other group had intact gut microbiota. Disruption of the gut microbiome in this manner has been shown to lead to reductions in tissue mechanical properties and whole bone strength in adulthood with only minor changes in bone geometry and density. In our study, disruption of the microbiome led to modifications in the abundance of microbial genes responsible for the synthesis of the bacterial cell wall; bacterially synthesized carbohydrates; and bacterially synthesized vitamins (vitamins B and K). Follow up analysis focused on vitamin K, a factor that has previously been associated with bone health. The vitamin K content of the cecum, liver and kidneys was decreased by about one-half when the microbiome was disrupted through antibiotic use compared to mice not treated with antibiotics. In addition, disruption of the microbiome also decreased the mineralization of the bone. This study illustrates the use of genomic analysis to link the microbiome to bone characteristics and implicates vitamin K that is produced by the gut bacteria as a regulator of bone matrix quality.

Technical Abstract: The genetic components of microbial species that inhabit the body are known collectively as the microbiome. Modifications to the microbiome have been implicated in disease processes throughout the body and have recently been shown to influence bone. Prior work has associated changes in the microbial taxonomy (phyla, class, species, etc.) in the gut with bone phenotypes but has provided limited information regarding mechanisms. With the goal of achieving a more mechanistic understanding of the effects of the microbiome on bone, we perform a metagenomic analysis of the gut microbiome that provides information on the functional capacity of the microbes (all microbial genes present) rather than only characterizing the microbial taxa. Male C57Bl/6 mice were subjected to disruption of the gut microbiota (referred to as Change in Microbiome mice) using oral antibiotics (from 4-16 weeks of age) or remained untreated (n=6-7/group). Disruption of the gut microbiome in this manner has been shown to lead to reductions in tissue mechanical properties and whole bone strength in adulthood with only minor changes in bone geometry and density. Change in microbiome led to modifications in the abundance of microbial genes responsible for the synthesis of the bacterial cell wall and capsule; bacterially synthesized carbohydrates; and bacterially synthesized vitamins (B and K) (p<0.01). Follow up analysis focused on vitamin K, a factor that has previously been associated with bone health. The vitamin K content of the cecum, liver and kidneys was primarily microbe-derived forms of vitamin K (menaquinones) and was decreased by 32-66% in Change Microbiome mice compared to untreated animals (p < 0.01). Bone mineral crystallinity was decreased (p=0.01) was decreased in Change in Microbiome mice (p < 0.001) and matrix carbonate-phosphoate ratio was increased. This study illustrates the use of metagenomic analysis to link the microbiome to bone phenotypes and implicates microbially synthesized vitamin-K as a regulator of bone matrix quality.