Xiaomeng You, PhD

She/Her/Hers
Postdoctoral Research Fellow
Orthopedics
Aging, Orthopaedic Surgery
Bone loss with aging is independent of age-related gut microbiome dysbiosis in mice

Principal Investigator: Julia F. Charles

Authors: Xiaomeng You, Jing Yan, Jeremy Herzog, Ross Campbell, Allison Hoke, Rasha Hammamieh, R. Balfour Sartor, Melissa A. Kacena, Nabarun Chakraborty, Julia F. Charles
Lay Abstract

Gut microbiome refers to the microorganisms that live in our digestive tract. Emerging evidence suggests an important role of the microbiome in bone health. As we age, our gut microbiome undergoes significant change, resulting in dysbiosis. At the same time, our bone deteriorates in bone mass and micro-architecture during the aging process. However, it is unclear whether microbiome dysbiosis with aging contributes to age-related bone loss. Here, we analyzed aging-associated alterations in fecal microbiome and investigated their roles in aging-related bone loss in a mouse model. We found that aging caused gut microbiome compositional and functional alterations in energy and nutrient metabolism, which may impact our bone health. We colonized germ-free (GF) mice, which mice are free of any microorganisms, with fecal microbiome from young and old healthy laboratory mice. We found that the effect of colonization on bone phenotypes was independent of the microbiome donor age. Moreover, the bone loss was similar in the comparison of old GF mice and their littermates with colonized microbiome or in the comparison of old GF mice and the same age of healthy laboratory mice. In conclusion, our study indicates age-related bone loss occurs independent of age-related gut microbial dysbiosis.

Scientific Abstract

Emerging evidence suggests an important role of the microbiome in bone health. However, it is unclear whether microbial dysbiosis with aging contributes to age-related bone loss. Here, age-specific microbial signatures were characterized and their roles in age-related bone loss were investigated in a murine model. 16s rRNA gene sequencing of fecal samples from 3- and 24-month old CB6F1 males indicated an age- dependent shift towards a Firmicutes-dominant community with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16s predicted metagenome and LC-MS fecal metabolome revealed enrichment of amino acid biosynthesis pathways in aged mice. Collectively, aging caused microbial taxonomic and functional dysbiosis in mice. Bone structure was assessed by micro-computed tomography 1 and 6 months after colonization of germ-free (GF) mice by fecal transplant from 3- or 24- month old specific pathogen-free (SPF) mice. The effect of colonization on bone phenotypes was independent of the microbiome donor age. Moreover, age related bone loss was similar in 24-month old GF mice compared to their littermates colonized at 8-week. Furthermore, bone loss from 3 to 24 months was indistinguishable in GF compared to SPF mice. In conclusion, our study indicates age-related bone loss occurs independent of age-related gut microbial dysbiosis.

Clinical Implications
Aging alters our gut microbiome composition and function, changing energy and nutrient metabolism, which is proposed to contribute to developing osteoporosis. However, in a mouse model we demonstrate that aging-related microbiome dysbiosis does not contribute to age-related bone loss.

If the PDF viewer does not load initially, please try refreshing the page.

Comments are closed.