Gut Microbiome and Bone Health: What's the Link?

The gut microbiome is the community of microorganisms that is found within the gut. It forms a dynamic ecosystem unique to each individual, which varies significantly between individuals depending on their lifestyle, genetics, diet, and environmental exposure¹. The microbiome plays a key role in digestion, in addition to important roles in metabolism and immunity. Dysbiosis of the gut, where the composition of the microbiome is altered, has been linked to several diseases, including obesity, type 2 diabetes, inflammatory bowel disease, and bone disorders such as osteoporosis^2,3.

This article explores the relationship between the gut microbiome and bone health, including how diet, lifestyle factors, and probiotics may contribute to improved bone health.

Understanding the Gut–Bone Axis

The gut microbiome and bone health are linked through a relationship known as the “gut-bone axis”. The microbiome plays an important role in regulating bone remodelling, which is the continual renewal of bone tissue to allow the skeleton to repair and adapt⁴. Bone remodelling requires a balance between bone formation and bone resorption; this is tightly regulated through a multi-layer system including the immune system, hormones, and metabolites^4,5.

The microbiome contributes to this regulation directly, through the release of metabolites, and indirectly, by modulating immune cells and hormones⁶. Dysbiosis can disrupt this axis, potentially affecting the balance between formation and resorption and contributing to degenerative bone diseases, such as osteoporosis⁴.

How the Gut Microbiome May Affect Bone Health

The gut microbiome may shape bone health through several mechanisms.

Calcium and mineral absorption

Bone tissue requires a continuous, adequate supply of nutrients, such as calcium, to build and maintain its structure. Calcium cannot be produced by the body and so is obtained from the diet and stored in bone. If dietary absorption is insufficient, calcium can be released from bone through increased bone resorption, which over time may contribute to reduced bone mass⁷.

The gut microbiome contributes to calcium absorption in several ways:

• The process of the gut microbiome fermenting dietary fibre results in a decrease in colonic pH. This increases the solubility of calcium salts⁸, enhancing calcium bioavailability and enabling the body to absorb sufficient calcium.
• Calcium is often found within macromolecules that resist digestion by human enzymes but can be broken down by enzymes found within gut bacteria, therefore unlocking dietary calcium that would otherwise be inaccessible.
• Various bile acids contribute to calcium absorption. The microbiome can induce bile acid remodelling, altering the ratio of different bile acids and affecting calcium absorption dynamics⁹.

Short-chain fatty acids

Short-chain fatty acids (SCFAs), which are metabolites produced by bacterial fermentation of dietary fibres, have a protective effect on bone mass through inhibiting the cells responsible for bone resorption, and so reducing bone loss¹⁰. Bone health is also protected by SCFAs via their anti-inflammatory effects and via promoting cells that contribute to building bone¹¹. Healthy microbiomes favour SCFA-producing bacteria, whereas dysbiosis reduces their abundance and lowers SCFA concentrations¹², reducing the protective effect of the gut microbiome on bone health.

Immune-mediated bone turnover and chronic inflammation

Gut microbiome dysbiosis compromises the gut barrier, enabling bacterial products that would normally be prevented from crossing the gut barrier to leak into the systemic circulation, repeatedly activating the immune system and leading to chronic inflammation¹³. Inflammation promotes bone resorption. Pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1, stimulate bone-resorbing cells, disrupting the balance between resorption and formation, and resulting in increased bone degradation¹⁴.

What Does the Evidence Show?

Multiple animal studies have demonstrated the effect that the gut microbiome has on bone health, with direct and indirect evidence supporting the theory that dysbiosis contributes to bone loss^15–17. Observational human studies are now reinforcing these findings, although causal proof and translation to clinical settings remain limited.

Clinical studies have demonstrated a link between the gut microbiome and bone health-related diseases, such as osteoporosis. In one observational study combining two large patient cohorts, stool samples of over 2000 people were analysed, and high-resolution imaging was carried out on the radius and tibia bones to assess the association between the gut microbiome and bone health. They found that certain genera were associated with reduced bone mineral density (BMD; indicative of reduced strength), but were explicit in that these findings do not demonstrate cause and effect¹⁸. A meta-analysis of postmenopausal women found a significant reduction in gut microbiome diversity in patients with osteoporosis, although again, this type of study cannot demonstrate causation¹⁹.

Interventional studies had mixed responses, with several finding that prebiotic and probiotic treatments for bone health had a positive effect, including increased BMD, reduced bone loss, increased calcium absorption, and positive biomarker changes^20–25. However, these results tended to be inconsistent, showed different results in different populations, had short intervention durations, and had limited mechanistic evidence.

Therefore, while the current evidence in humans points towards a link between the gut microbiome and bone health, evidence gaps and a lack of proof of causation limit the conclusions from these studies.

Diet and Lifestyle Factors

While the exact effects of the microbiome on bone health have not been elucidated, altering diet and lifestyle factors has the potential to positively affect many aspects of health, including bone health and the microbiome. These factors may include increasing:

• Dietary fibre, which is thought to promote a shift in the microbiome towards beneficial SCFA-producing bacteria that may contribute to protecting bone mass by inhibiting the cells responsible for bone resorption^10,26.
• Plant diversity, which is thought to increase microbiome diversity and result in a higher abundance of SCFA-producing bacteria²⁷.
• Calcium, which directly contributes to bone strength, as reduced calcium intake results in calcium being reabsorbed from the bones, reducing bone mass⁷.
• Vitamin D, which enables calcium absorption from the diet and also increases gut microbiome diversity^28,29.
• Exercise, which stimulates the cells that build bone, reducing the risk of imbalance and excessive bone resorption³⁰. Exercise also promotes microbial diversity and beneficial, SCFA-producing bacteria ³¹.

Probiotics and Bone Health

Modulating the microbiome to increase diversity and shift towards more beneficial bacteria is thought to have a positive impact on many health features, potentially including bone health. Probiotics are live microorganisms that are thought to provide health benefits by modulating the microbiome, increasing the population of beneficial microbes, and protecting the gut barrier³².

The clinical evidence supporting the use of probiotics for bone health includes:

• An RCT by Lambert et al. found that isoflavone combined with a mixture of probiotics significantly reduced BMD loss in several areas and decreased bone resorption markers in postmenopausal osteopenic women²².
• An RCT by Takimoto et al. found that Bacillus subtilis C-3102 increased hip BMD and reduced bone resorption over 24 weeks in healthy postmenopausal women²³.
• A multicentre RCT by Jansson et al. found that a three-strain Lactobacillus probiotic reduced lumbar spine BMD loss over 12 months in postmenopausal women²⁴.
• An RCT by Nilsson et al. found that Lactobacillus reuteri 6475 reduced loss of tibial volumetric BMD in older women with low BMD over 12 months²⁵.

Meta-analyses combining different probiotic studies have found that results are modest but statistically significant in many cases^33,34. However, high heterogeneity in studies makes any conclusive strain-specific claims difficult. Ongoing research with longer and larger trials is needed to demonstrate a conclusive causal link between probiotics and improved bone health, but the initial results are promising.

Clinical Takeaways

The evidence so far suggests that gut health and bone density may be linked, with the gut-bone axis providing multiple possible mechanisms via which bone health is improved, including calcium bioavailability, SCFA production, and immune regulation. However, most human evidence remains observational or based on small interventional trials, meaning that causation has not been established.

As a result, diet and lifestyle choices remain the most effective methods of protecting bone health. Adequate calcium and vitamin D intake, a fibre-rich and diverse diet, and regular exercise are well-supported strategies that support both bone health and a healthy microbiome. Microbiome-targeting interventions, such as probiotics, are an emerging area with encouraging but preliminary results. Larger, long-term trials will be needed before specific microbiome-based recommendations can be made for bone health in clinical practice.

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