The trajectory of bone density over time is affected by the balance of activities between osteoblast cells that build bone and osteoclast cells that break down bone. With age, osteoclast activity begins to outweigh osteoblast activity, leading eventually to osteoporosis. There is some evidence for this age-related loss of bone density to be influenced by the composition of the gut microbiome. To the degree in which everything in aging is connected by mechanisms of chronic inflammation, this makes some sense: a more inflammatory gut microbiome could make everything worse, including osteoporosis. Here, however, researchers use germ-free mice to show that dramatic differences in the presence of a gut microbiome make little difference to age-related loss of bone density. This argues for a minimal role for the gut microbiome, inflammation or otherwise.
Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss.
16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice.
To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors' age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.
Link: https://doi.org/10.1038/s41413-024-00366-0
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