The educational content in this post, elaborated in collaboration with BioGaia, was independently developed and approved by the GMFH publishing team and editorial board.

Emerging science looks to gut microbiome to make bones less brittle

Alterations in gut microbiome composition and functions have been reported in conditions that lead to bone loss or increase fracture risk such as a poor diet, obesity and inflammatory diseases. That is why scientists have started to speculate that there might be a relationship between the gut microbiota and bones.

The first data looking at the connection between the gut microbiota and bones comes from studies in mice showing how the gut microbiome can affect bone strength, probably through microbe-derived vitamin K and other pathways such as short-chain fatty acids.

Further evidence suggesting a possible link between bone health and the gut microbiota comes from the way the evolution of bone mineral density across the lifespan mirrors changes in gut microbiota diversity, with a decrease in microbial diversity and bone mineral density in late adulthood and menopause. When trying to better understand how the gut is connected to bones, scientists have also found that an altered gut barrier function can shape the inflammatory immune responses that drive the growth of cells involved in bone destruction rather than bone formation.

The evidence in humans on the role of the gut microbiome in bone metabolism is limited. So far, it has come from the observation that following certain dietary patterns that feature a high amount of plant-based foods, such as the Mediterranean diet, are associated with a reduction in fracture risk, probably mediated by the gut microbiome, and small intervention studies examining the effect of specific probiotics on bone loss.

 

What are the two most important factors proven to keep bones strong

Science has proven that diet and exercise are the two most important factors for minimizing bone loss and thus preventing osteoporosis. Indeed, in terms of diet, proteins, calcium, vitamin D and vitamin K are all nutrients that are important for bone strength.

Dietary protein, whether animal or plant-based, has a beneficial effect on bone health. Yet if ingested in low amounts, it does not help prevent bone loss, particularly after the age of 40, which is when bone loss begins. It is therefore important to ensure that diets with high nutrient density include an adequate amount of protein, along with other nutrients that are important for bones such as calcium, vitamin D and vitamin K.

Calcium is the building material for strong bones and teeth. Dairy products and canned fish that includes soft bones (such as sardines) provide the most available source of calcium. The best way to achieve the recommended daily amount of calcium is by including three daily servings of dairy products (i.e., one glass of milk or plant-based drink enriched with calcium, two yoghurts and two wedges of semi-cured cheese). If you are vegan or vegetarian you can also find calcium in almonds, leafy green vegetables (e.g., spinach and kale) and citrus.

Vitamin D helps your intestine absorb calcium and deposit it in cartilage to form bones. The sun is your best source of vitamin D, which you can get safely at midday as the sun is at its highest point. That means that for Caucasian adults, 15 minutes of midday sunlight exposure in the summer three times per week is enough to maintain healthy levels of vitamin D. However, recent surveys from highly sunlight exposed countries (e.g., Greece, Cyprus and Spain) show a generalized vitamin D deficiency. This trend highlights that a combination of sunlight exposure and a diet with foods that contain vitamin D (e.g., eggs, fish oils, milk, butter) and fortified foods is needed for ensuring the right vitamin D exposure in the general population.

Vitamin K comes in two forms (K1 and K2) and is also important for activating proteins involved in bone formation and mineralization. While vitamin K1 is found mainly in leafy green and cruciferous vegetables, vitamin K2 is produced by bacteria and is also found in hard cheeses, chicken, pork and fermented foods. While it seems that vitamin K2 may have a more protective effect on bone than vitamin K1, studies exploring the role of vitamin K in the form of supplements yielded mixed results.

Exercise is the second most important ingredient for building healthy bones. In particular, exercises where your body bears its own weight (e.g., walking and tennis) appear to be the most effective for preventing osteoporosis.

 

Is there a role for probiotics in taking care of bone health?

Based on the emerging studies that show that the gut microbiota is partly involved in bone health, scientists suggest that specific probiotics can be considered alongside calcium and vitamin D.

Some randomized controlled trials have shown that specific strains of Bacillus and Lactobacillus, alone or in combination with other bone-friendly nutrients, such as calcium, vitamin D and isoflavones, can impact bone health. However, it is difficult to attribute the effect on bones to probiotics alone.

The effects of probiotics on bone mineral density and the process of bone resorption followed by replacement by new bone (i.e., bone turnover) have been studied mainly in healthy postmenopausal women. That is the case, for instance, of a double-blind, placebo-controlled trial that examined the effect of the probiotic Limosilactobacillus reuteri ATCC PTA 6475 on bone loss in women with a mean age of 76 who had reduced bone mass. After a year, the probiotic resulted in a reduced loss of bone mineral density at the tibia compared to the group taking placebo.

In another randomized controlled trial, a combination of three Lactobacillus strains taken for one year showed improvement in lumbar bone loss, while another study with the probiotic Bacillus subtilis C-3102 for six months showed increased hip bone mineral density and changes in bone resorption markers. Overall, the magnitude of the effect in published studies is modest and none tested the effect of probiotics on new fractures.

In addition to probiotics in the form of food supplements, fermented dairy products such as cheese, yoghurt and kefir can also improve bone traits thanks to the calcium, proteins, prebiotics and probiotics contained within.

Most available treatments for osteoporosis focus on improving bone mineral density. In contrast, treatments that improve bone matrix quality are lacking. Directly or indirectly influencing the gut microbiome through probiotics could help make bone matrix less brittle in the context of a balanced diet and high-impact weight-bearing exercises.

 

Take-home messages

  • Emerging evidence suggests a connection between the gut microbiota and bones.
  • Diet and exercise are the two most important factors proven to keep bones strong.
  • Specific probiotic strains, alone or in combination with nutrients with a known positive impact on bone health, have been shown to modestly improve bone mineral density, yet their benefits for bone fractures in the long term is still unknown.

 

 

References:

Guss JD, Horsfield MW, Fontenele FF, et al. Alterations to the gut microbiome impair bone strength and tissue material properties. J Bone Miner Res. 2017; 32(6):1343-1353. doi: 10.1002/jbmr.3114.

Guss JD, Taylor E, Rouse Z, et al. The microbial metagenome and bone tissue composition in mice with microbiome-induced reductions in bone strength. Bone. 2019; 127:146-154. doi: 10.1016/j.bone.2019.06.010.

Zaiss MM, Jones RM, Schett G, et al. The gut-bone axis: how bacterial metabolites bridge the distance. J Clin Invest. 2019; 129(8):3018-3028. doi: 10.1172/JCI128521.

Cooney OD, Nagareddy PR, Murphy AJ, et al. Healthy gut, healthy bones: targeting the gut microbiome to promote bone health. Front Endocrinol. 2020; 11:620466. doi: 10.3389/fendo.2020.620466.

Cronin O, Lanham-New SA, Corfe BM, et al. Role of the microbiome in regulating bone metabolism and susceptibility to osteoporosis. Calcif Tissue Int. 2022; 110(3):273-284. doi: 10.1007/s00223-021-00924-2.

Wallace TC. Optimizing dietary protein for lifelong bone health. A paradox unraveled. Nutrition Today. 2019; 54(3):107-115. doi: 10.1097/NT.0000000000000340.

Raman R. How to safely get vitamin D from sunlight. Healthline, 2018. Available: https://www.healthline.com/nutrition/vitamin-d-from-sun

Lips P, van Schoor NM, de Jongh RT. Diet, sun, and lifestyle as determinants of vitamin D status. Ann N Y Acad Sci. 2014; 1317:92-98. doi: 10.1111/nyas.12443.

Cleveland Clinic. Do you need vitamin K supplements for your bone health? 2019. Available: https://health.clevelandclinic.org/do-you-need-vitamin-k-supplements-for-your-bone-health/

Harvard Health Publishing. Harvard Medical School. Keeping bones strong. 2018. Available: https://www.health.harvard.edu/staying-healthy/keeping-bones-strong

Rizzoli R, Biver E. Are probiotics the new calcium and vitamin D for bone health? Curr Osteoporos Rep. 2020; 18(3):273-284. doi: 10.1007/s11914-020-00591-6.

Nilsson AG, Sundh D, Bäckhed F, et al. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018; 284(3):307-317. doi: 10.1111/joim.12805.

Takimoto T, Hatanaka M, Hoshino T, et al. Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: a randomized, placebo-controlled, double-blind clinical trial. Biosci Microbiota Food Health. 2018;37(4):87-96. doi: 10.12938/bmfh.18-006.