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The Relation Between Bone Health in Women and Gut Flora

Do you feel inflammation in your joints, aches, pains and swelling throughout the body or frequent bloating and distention after meals? Then you might have lost much diversity in your diets that have impacted your gut microbiome. This, compounded by a diet high in calories, low intake of fiber or shortness of nutrients, might be causing inflammation.

Trillions of bacteria that line up your gut have a mutually beneficial symbiotic relationship with your body, which plays a pivotal role in maintenance of your overall health. When the balance and diversity of microbiome is disturbed due to certain factors, human health suffers. 

Gut Microbiota Affects Bone Health

Accumulative investigations prove that the gut microbiota closely regulates bone metabolism. It also monitors absorption of bone-related minerals under physiological conditions, while being involved in osteoporosis.

Wang et al. conducted a 16S rRNA gene sequencing to detect the composition and diversity changes of gut microbiota in patients suffering from primary osteoporosis and primary osteopenia. This supported the view that bone health might be influenced by the gut microbiota. 

Effect of Gut Bacteria on Calcium Absorption

Food is the only source of calcium, the main mineral for human bones. The calcium in food is absorbed through the intestinal wall. The effect of gut microbiota on calcium is mainly controlled by short-chain fatty acids (SCFAs).

The colon is the main site of SCFA production and SCFAs are the main products of intestinal bacterial fermentation in organisms, including acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid. Gut bacteria break down dietary fiber into SCFAs, which, in turn, increase the absorption of calcium in the intestinal wall by reducing intestinal pH, thus increasing bone mass.

Vitamin D promotes absorption of calcium and phosphorus absorption in the gut, as well as bone calcification. Research has proved that vitamin D deficiency could lead to a decrease in the proportion of gut bacteria from Firmicutes and Deferribacteres groups, and is more likely to induce colitis.

The same study found that inflammation was controlled after vitamin D supplementation or antibiotic treatment. So, studies sustain the notion that vitamin D manages the development of osteoporosis by controlling the gut microbiome directly.  Moreover, a small clinical trial in post-menopausal women revealed a dose-response effect in bone calcium retention with SCFA dose. 

Research revealed bacteria and bacterial products can modulate processes of bone gain and bone loss via effects on both bone cells – osteoblasts and osteoclasts. Other than these discoveries, the gut microbiota also modulates bone morphology, ultimately affecting bone strength and consequently fracture risk. 

Particular attention has been placed on the skeletal changes occurring during the menopausal transition in women, typically characterized by bone loss. After the onset of menopause in women, the normal bone turnover cycle is impaired leading to a decline in bone mass. One in three women over age 50 worldwide experiences osteoporotic fractures as a consequence of menopause. 

How Probiotic Supplementation can Affect the Gut-Bone Axis

Recently, probiotics supplemented with the isoflavone contributing red clover extract RCE, which has estrogen receptor affinity, have shown to decrease bone loss in postmenopausal osteopenic women supplemented with calcium, magnesium, and calcitriol, strengthening the hopes about the potential of the osteomicrobiology field. However, more studies in humans are needed.

Microbiome, genetic and metabolic studies in large populations are underway and will certainly prove how the microbiome determines skeletal health.

IGF-1 (insulin-like growth factor), produced in the liver after food intake and regulated by microbes, was the first metabolite identified as a linker in the gut-bone axis.  Again, Peptide YY, a gastrointestinal hormone, is secreted from the endocrine L cells and is negatively associated with the total body and hip BMD in premenopausal women.

Osteoporosis, a systemic and metabolic bone disease, is characterized by a decrease in bone mass and deterioration of bone tissue that leads to bone fragility and susceptibility to fracture. OP can occur in both sexes and at any age, but most common in postmenopausal women.

Evidence has suggested that gut microbiota is linked to bone metabolism and the absorption of bone-related minerals under physiological conditions, while being involved in osteoporosis pathologically.  Heredity, aging, inflammation, and hyperparathyroidism are common causes of osteoporosis and menopause is a major risk factor for osteoporosis. There is elevated risk of wrist, hip, or spine fractures due to osteoporosis. As disorder of the gut microbiome is one of the important pathogenesis of OP, treatment strategies targeting the gut microbiota may be promising. 

Mechanisms Through which Microbiota Affects Bone Health

  • Immune-mediated  

Intestinal microflora impacts bone health via the immune system, which regulates the development of bone marrow cells and inflammatory cytokines. Intestinal flora also affect diseases such as immune system-induced rheumatoid arthritis and systemic lupus erythematosus.

  • Endocrine-mediated  

Intestinal microbiota as a virtual “endocrine organ” have certain effects on bone health. Sex hormones are significant in maintaining bone homeostasis, and a lack of these hormones can lead to a decrease of microbial flora in the gut, thus increasing bone loss and affecting bone formation. 

  • Changes in intestinal microbiome 

Changes in gut microbiome and their metabolites affect bone health directly or indirectly. The effects of microbial flora, probiotics, antibiotics, and dietary nutrition also impacts bone health. Probiotic dietary supplements containing Bacillus licheniformis and B. subtilis increased the diversity of gut microbiota. 

Parting Words

Correlation between intestinal microbial flora and bone health paves the way for further research on the treatment of bone diseases and the beneficial effects of probiotics in terms of increasing bone mass. This provides a basis for treating hereditary bone diseases, which involve abnormal bone, cartilage, joint, and other related tissues due to pathogenic mutations in genes.

The relationship between pathogenic mutations that cause genetic bone diseases and intestinal microbiota needs to be studied further. There is mounting evidence of data relating intestinal microbiome to bone disease in osteoporosis and RA. Osteoarthritis, despite some suggestive findings, received little attention to date. Bone is considered a nutritionally regulated tissue and diet has a great impact on bone health, which is often overlooked.  Given this association, diet is an important confounding factor when assessing the impact of changes in gut microbiome on bone health.  A healthy diet represented by prebiotics and probiotics will beneficially affect the whole gut microbiota, maintain intestinal homeostasis, improve intestinal absorption, and play a positive role in regulating bone loss.