Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
National Gnotobiotic Rodent Resource Center, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Bone Res. 2024 Nov 11;12(1):65. doi: 10.1038/s41413-024-00366-0.
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.
新兴证据表明肠道微生物组在骨骼健康中起着重要作用。衰老是公认的影响肠道微生物组的关键因素。在这项研究中，我们研究了年龄相关的微生物变化是否导致 CB6F1 小鼠的年龄相关性骨丢失。与 1 个月龄时经粪便移植定植的同窝仔相比，24 月龄无菌（GF）小鼠的骨骼表型没有区别。此外，GF 小鼠和特定病原体无菌（SPF）小鼠从 3 月龄到 24 月龄的骨丢失相当。因此，GF 小鼠不能免受年龄相关性骨丢失的影响。3 月龄和 24 月龄 SPF 雄性小鼠粪便样本的 16S rRNA 基因测序表明，随着能量和营养代谢潜力的改变，微生物发生了年龄依赖性变化。对 16S 预测宏基因组功能和 LC-MS 粪便代谢组学的综合分析表明，老年小鼠中富含蛋白质和氨基酸生物合成途径。微生物 S-腺苷甲硫氨酸代谢在老年小鼠中增加，这与宿主衰老过程先前有关。总的来说，衰老导致了小鼠微生物分类和功能的改变。为了证明年轻和年老微生物组对骨骼的功能重要性，我们用 3 个月和 24 个月龄 SPF 供体小鼠的粪便微生物组对 GF 小鼠进行了 1 个月和 8 个月的定植。微生物定植对骨骼表型的影响与微生物供体的年龄无关。总之，我们的研究表明，年龄相关性骨丢失与肠道微生物组无关。
