Components of the gut microbiome that influence bone tissue-level strength

Authors: LUNA, MARYSOL - Cornell University; GUSS, JASON - Cornell University; VASQUEZ-BOLANOS, LAURA - Cornell University; CASTANEDA, MACY - Cornell University; VARGAS ROJAS, MANUELA - Cornell University; STRONG, JASMIN - Cornell University; ALABI, DENISE - Cornell University; DORNEVIL, SOPHIE - Cornell University; NIXON, JACOB - Cornell University; TAYLOR, ERIC - Cornell University; DONNELLY, EVE - Cornell University; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BICALHO, RODRIGO - Cornell University; HERNANDEZ, CHRISTOPHER - Cornell University

Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/14/2021
Publication Date: 5/17/2021
Citation: Luna, M., Guss, J., Vasquez-Bolanos, L., Castaneda, M., Vargas Rojas, M., Strong, J.M., Alabi, D.A., Dornevil, S., Nixon, J.C., Taylor, E.A., Donnelly, E., Fu, X., Shea, K., Booth, S.L., Bicalho, R.C., Hernandez, C.J. 2021. Components of the gut microbiome that influence bone tissue-level strength. Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.4341.
DOI: https://doi.org/10.1002/jbmr.4341

Interpretive Summary: The intestinal microbiota is comprised of bacteria and other microorganisms that reside within the intestine. Evidence suggests the composition of intestinal microbiota can influence bone health, but it is not known what microbial components are most influential. Mice were treated with different types and combinations of antibiotics for 4 weeks to deplete specific bacteria in their intestine, and then were tested for bone strength and other measures of bone tissue quality. Of the distinct gut microbiota created with the different interventions, one group was associated with impaired bone tissue strength whereas a different group was associated with increased bone tissue-level strength. These findings suggest interventions that target specific intestinal microbes may provide a new therapeutic target to address bone fragility.

Technical Abstract: Modifications to the constituents of the gut microbiome influence bone density and tissue-level strength, but the specific microbial components that influence tissue-level strength in bone are not known. Here we selectively modify constituents of the gut microbiota using narrow spectrum antibiotics to identify components of the microbiome associated with changes in bone mechanical and material properties. Male C57BL/6J mice (4 weeks) were divided into seven groups (n=7-10/group) and had taxa within the gut microbiome removed through dosing with: 1) ampicillin; 2) neomycin; 3) vancomycin; 4) metronidazole; 5) a cocktail of all four antibiotics together (with zero calorie sweetener to ensure intake); 6) zero-calorie sweetener only or; 7) no additive (untreated) for 12 weeks. Individual antibiotics remove only some taxa from the gut while the cocktail of all four removes almost all microbes. After accounting for differences in geometry, whole bone strength was reduced in animals with gut microbiome modified by neomycin (-28%, p=0.002) and was increased in the group in which the gut microbiome was altered by sweetener alone (+ 39%, p < 0.001). Analysis of the fecal microbiota detected seven lower ranked taxa differentially abundant in animals with impaired tissue-level strength and 14 differentially abundant taxa associated with increased tissue-level strength. Histological and serum markers of bone turnover and trabecular BV/TV did not differ among groups. These findings demonstrate that modifications to the taxonomic components of the gut microbiome have the potential to decrease or increase tissue-level strength of bone independent of bone quantity and without noticeable changes in bone turnover.