Aging bones and microbiome: unraveling the myth
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Aging bones and microbiome: unraveling the myth

30/12/2024 TranSpread

Osteoporosis is a major health concern worldwide, particularly in aging populations. Despite pharmacological advancements, challenges like side effects, costs, and limited accessibility reduce adherence to treatments. Recently, the gut microbiome has gained attention for its potential role in bone metabolism. Yet, aging complicates its stability and influence, raising the need to explore alternative mechanisms behind bone loss. Given these challenges, researchers aimed to investigate non-microbial contributors to age-related bone deterioration.

A collaborative study led by Harvard Medical School, published (DOI: 10.1038/s41413-024-00366-0) in Bone Research on November 08, 2024, tackled this question. Using advanced genetic sequencing and metabolomic tools, scientists examined bone health in CB6F1 mice under germ-free and microbiome-colonized conditions to assess the microbiome’s impact on bone loss during aging.

The study revealed that bone loss in germ-free mice mirrored that of their microbiome-colonized counterparts, debunking the belief that gut microbes significantly influence age-related bone deterioration. Over 21 months, both groups exhibited comparable declines in trabecular bone volume and cortical thickness, underscoring that bone loss occurs independently of gut microbiota. Although age-related shifts in microbial composition and function were observed—such as increased amino acid and protein biosynthesis—these changes did not affect bone health. Even microbiota transplants from young or old donors into germ-free mice had no discernible impact, regardless of donor age or colonization duration. These findings redirect attention to other biological pathways as potential drivers of osteoporosis.

Dr. Xiaomeng You, lead researcher, remarked, “This study overturns long-standing beliefs about the gut microbiome’s role in age-related bone loss. By refocusing on other mechanisms, we aim to open new pathways for effective osteoporosis treatments.” The team highlighted the microbiome's influence on other health aspects but emphasized its limited role in bone health during aging.

These results pave the way for rethinking osteoporosis interventions, suggesting that genetic, hormonal, or environmental factors may hold greater significance. Future research could leverage these insights to develop innovative therapies, ultimately improving care for aging populations. While the microbiome remains a crucial research frontier, this study underscores the importance of broadening the lens to fully understand bone health.

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References

DOI

10.1038/s41413-024-00366-0

Original Source URL

https://doi.org/10.1038/s41413-024-00366-0

Funding information

This work was supported by NIH grants R01 AG046257 (JFC), the Orthopaedic Scholar Fund, the Department of Orthopaedic Surgery, Brigham and Women’s Hospital, P30 AR075042 and the Joint Biology Consortium funded by P30-AR070253. Gnotobiotic studies were performed at National Gnotobiotic Rodent Resource Center at University of North Carolina at Chapel Hill, funded by P40-OD010995, P30-DK034987, and Crohn’s and Colitis Foundation.

About Bone Research

Bone Research was founded in 2013. As a new English-language periodical, Bone Research focuses on basic and clinical aspects of bone biology, pathophysiology and regeneration, and supports the foremost discoveries resulting from basic investigations and clinical research related to bone. The aim of the Journal is to foster the worldwide dissemination of research in bone-related physiology, pathology, diseases and treatment.

Paper title: Bone loss with aging is independent of gut microbiome in mice
Attached files
  • Effect of colonization on bone phenotype of germ-free mice is independent of age of donor microbiome. Effect of colonization for 1 month on trabecular bone volume fraction (Tb. BV/TV), cortical thickness (Ct. Th), cortical area (Ct. Ar), serum P1NP and CTX-1 in young adult (2-month-old, a–e) and skeletal immature (1-month-old, f–j) females is shown. Consequences of 8 months colonization on Tb. BV/TV, Ct. Th, and Ct. Ar are shown for (k–m) female and (p–r) male mice. n, o Serum P1NP and CTX-1 is shown in female after 8 months colonization. s Representative 3D images of femur trabecular bone are shown. Data are represented as mean ± SEM. One-way ANOVA or Kruskal-Wallis test with Tukey post hoc was performed. *P < 0.05, **P < 0.01, ***P < 0.001, ns, not statistically significant. For (a–e): GF, n = 11; Col with 3-month, n = 14; Col with 24-month, n = 14. For (f–j): GF = 8; Col with 3-month, n = 9; Col with 24-month, n = 8. For (k–o): GF, n = 12; Col with 3-month, n = 7; Col with 24-month, n = 8. For (p–r): n = 8 per group. 4 data in (e) and 5 data in (n) and (o) were missing due to insufficient sample collection.
30/12/2024 TranSpread
Regions: North America, United States, Asia, China
Keywords: Health, Medical

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