The emerging field of osteomicrobiology, which explores the connection between gut microbiota and skeletal health, presents a promising avenue for preventing and treating osteoporosis. Bone tissue is continuously undergoing a process known as bone remodeling, in which damaged bone is resorbed (osteoclasts), and new bone is formed (osteoblasts). This dynamic equilibrium between bone formation and resorption plays a crucial role in maintaining bone health. An imbalance occurs when the rate of bone resorption surpasses that of bone formation, resulting in decreased bone density and strength, leading to conditions known as osteopenia and osteoporosis. Several factors influence the balance between bone formation and resorption. For instance, vitamin D, K, and short chain fatty acids, help to maintain bone structure by increasing calcium absorption and bone mineralization.
More recently, the gut microbiome has gained attention as a potential target for improving bone strength through involving microbe-derived vitamin K and short-chain fatty acids (SCFAs). It seems that SCFAs released by the gut microbiota not only have direct effects on bone remodeling, but may also affect the immune response (T cells and cytokines) that can influence the activity of osteoclasts and osteoblasts. In line with the gut-bone axis, interventions targeting gut microbiota, such as probiotics or antibiotics, have been found to affect bone remodeling and thus emerge as a novel promising therapy for osteoporosis.
A new observational study based on two large cohorts delves into potential links between the gut microbiome and skeletal health. Douglas P. Kiel, MD, a researcher at the Marcus Institute for Aging Research, and affiliated to the Harvard Medical School used high-resolution peripheral quantitative computed tomography scans of the radius and tibia, a cutting-edge imaging technique that provides detailed insights into the microarchitecture of the bone, to evaluate the volumetric bone mineral density. The investigation involved two cohorts: the Framingham Heart Study (FHS), encompassing 1,227 individuals aged 32 to 89, and the Osteoporosis in Men Study (MrOS), which included 836 participants aged 78 to 98.
In the FHS cohort, the researchers observed a negative association between the abundance of a Clostridiales bacterium DTU089, Marvinbryantia, Blautia, and Akkermansia and bone measures. In the cohort with older individuals, the authors found that increased abundance of the genera Methanobrevibacter and DTU089 was associated with lower cortical bone density, while increased abundance of Lachnospiraceae NK4A136 group was associated with greater cortical bone density. DTU089 was negatively associated with trabecular and tibia bone measures. Interestingly, DTU089 was recently found to be more abundant in people with lower protein intake and lower physical activity, which are known factors involved in bone fragility.
The researchers also went one step further and combined data from the two cohorts to explore the link between gut microbiota and bone density. They found that a greater microbial abundance of Akkermansia and DTU089 was associated with lower radius total bone density, and tibia cortical bone density, respectively. Additionally, the researchers found that higher abundances of Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical bone density. These findings suggest that the gut microbiome may play a role in bone health, with particular microbial strains impacting bone density measures.
Ultimately, the study led to predictions regarding the metabolic processes linked to the abundance of specific bacteria. Notably, a higher prevalence of pathways related to histidine, purine, and pyrimidine biosynthesis was associated with a modest elevation in tibia bone density. The histidine biosynthesis pathway participates in regulating inflammation and immune response, while purine and pyrimidine biosynthesis pathways participate in cell growth and proliferation. Among these pathways, purine metabolism is known to influence the balance between bone formation and resorption.
The consistent associations unveiled between gut microbiota and skeletal measures suggest a connection between the gut microbiome and skeletal metabolism. However, it is essential to emphasize that these associations were predicted, and further research is needed to establish causation. These discoveries pave the way for the development of targeted gut microbiota therapeutic strategies aimed at preventing and treating osteoporosis.
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