Connecting Bone and Gut Health

The various tissues of the skeletal system are intricately connected to the health of multiple body systems, including the gastrointestinal track and the gut microbiome. Bone-related disorders such as osteoporosis, rheumatoid arthritis, and osteoarthritis have been associated with dysbiosis of gut microbiota1,2 while an increased prevalence and development risk of osteoporosis or low bone mineral density has been reported in patients with chronic diseases such as inflammatory bowel disease.3,4 From nutrient absorption and metabolite synthesis to immunomodulation and regulatory hormones, a healthy intestinal microbiome influences bone homeostasis,5,6 and if the bone remodeling cycle is imbalanced, with resorption rates outpacing formation, an impaired gut may be involved. How can healthy diets that include fiber and a variety of prebiotic foods not only support gut balance and beneficial microbiota but also help optimize bone health?

Gut Microbiome Impact on Bone

Research investigations continue to elucidate the mechanisms relating gut microbiota and bone cell communications. Studies indicate that the microbial landscape impacts nutrient absorption and metabolism, with some commensal bacteria believed to promote the intake of bone-related minerals such as calcium, magnesium, and phosphorous.5,7 In addition, during their fermentation process, intestinal microbes produce numerous bioactive compounds that are important for bone health, including B vitamins and vitamin K.5,8

Short-chain fatty acids (SCFA) are additional beneficial metabolites produced by gut bacteria that play a regulatory role in osteocyte metabolism and bone mass. Studies indicate that SCFAs inhibit bone resorption through the regulation of osteoclast differentiation.5 Further, an abundant SCFA, butyrate, is believed to promote osteoblast differentiation and stimulate mineralized nodule formation to support bone growth.9 Butyrate has also been reported to directly stimulate osteoblast activation and bone formation through the regulation of regulatory T cells (Tregs).9 And a recent animal study found that butyrate was required for parathyroid hormone (PTH) to stimulate bone formation and increase bone mass through an increased number of bone marrow Tregs.10

Research suggests that gut-derived hormones also play an important role in bone homeostasis and metabolism.11 To further the investigation of this complex relationship, a small 2021 cross-over clinical trial (n=14) examined postprandial associations between two bone-remodeling biomarkers and the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY).12 Researchers found that one out of the two bone remodeling biomarkers was positively associated with GIP and GLP-1 and inversely associated with PYY.12 While no firm conclusions could be stated, the study supported the link between gut hormones and bone metabolism in humans.

Mediterranean Diet, Prebiotic Foods, and Probiotics

Following a nutrient-dense diet that includes a variety of colorful fruits and vegetables, whole grains, and healthy fats has demonstrated positive effects on several health parameters.13,14 The Mediterranean diet is one well-studied example of a nutrition plan that has also been evaluated specific to its impact on bone health. A 2022 systematic review and meta-analysis (eight observational studies with 13,209 participants) investigated the dose-response relationship between adherence to the Mediterranean diet and bone mineral density values in adults.15 Results indicated that greater adherence to the Mediterranean diet was associated with small but statistically significant increases in bone mass density at the lumbar spine, femoral neck, hip, trochanter, and whole body.15

Consuming plant-based foods and their soluble fibers promotes fermentation by the gut microbial community, leading to the production of beneficial metabolites such as SCFAs. In addition, prebiotics are present in plant-based, fiber-rich foods, and these nutrients are selectively used by the gut microbiota. Inulin and oligofructose are examples of prebiotics that naturally exist in foods such as Jerusalem artichokes, asparagus, onions, and bananas. A 2021 systematic review examined the health impact of these inulin-type fructans in healthy adult populations.16 The inulin-type fructans were found to promote the abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus and had a range of beneficial health effects, from improved intestinal barrier function to increased absorption of the bone-related nutrients calcium and magnesium.16

The use of probiotics to support healthy bones has shown some conflicting results depending on dosage, bacterial species, and patient populations. A recent systematic review and meta-analysis evaluated the probiotic consumption effects on bone health from 44 studies, 37 of which were animal models.17 Researchers found that in clinical trials, probiotic consumption (primarily strains of the Lactobacillus species tested on women aged 50 years or older) affected bone health parameters such as serum calcium levels, urinary calcium levels, and PTH levels; however, spinal and total hip bone mineral density was not significantly affected.17 In animal testing, most studies reported beneficial effects of probiotic feeding on bone health parameters and status with strains of Bifidobacterium and Lactobacillus.17

As the research continues to develop, modulating and balancing the gut microbiome through nutritional approaches is a promising component for bone health interventions.7,18,19 Learn more about this topic and other innovative functional medicine approaches at the 2024 Annual International Conference (AIC): Repair, Restore, Regenerate: Healing of the Micro and the Macro Through Functional Medicine.

References

  1. Bhardwaj A, Sapra L, Tiwari A, Mishra PK, Sharma S, Srivastava RK. “Osteomicrobiology”: the nexus between bone and bugs. Front Microbiol. 2022;12:812466. doi:3389/fmicb.2021.812466
  2. Akinsuyi OS, Roesch LFW. Meta-analysis reveals compositional and functional microbial changes associated with osteoporosis. Microbiol Spectr. 2023;11(3):e0032223. doi:1128/spectrum.00322-23
  3. Szafors P, Che H, Barnetche T, et al. Risk of fracture and low bone mineral density in adults with inflammatory bowel diseases. A systematic literature review with meta-analysis. Osteoporos Int. 2018;29(11):2389-2397. doi:1007/s00198-018-4586-6
  4. Kärnsund S, Lo B, Bendtsen F, Holm J, Burisch J. Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease. World J Gastroenterol. 2020;26(35):5362-5374. doi:3748/wjg.v26.i35.5362
  5. Ding K, Hua F, Ding W. Gut microbiome and osteoporosis. Aging Dis. 2020;11(2):438-447. doi:14336/AD.2019.0523
  6. Wallimann A, Magrath W, Thompson K, et al. Gut microbial-derived short-chain fatty acids and bone: a potential role in fracture healing. Eur Cell Mater. 2021;41:454-470. doi:22203/eCM.v041a29
  7. de Sire A, de Sire R, Curci C, Castiglione F, Wahli W. Role of dietary supplements and probiotics in modulating microbiota and bone health: the gut-bone axis. Cells. 2022;11(4):743. doi:3390/cells11040743
  8. Uebanso T, Shimohata T, Mawatari K, Takahashi A. Functional roles of B-vitamins in the gut and gut microbiome. Mol Nutr Food Res. 2020;64(18):e2000426. doi:1002/mnfr.202000426
  9. Chen Y, Wang X, Zhang C, Liu Z, Li C, Ren Z. Gut microbiota and bone diseases: a growing partnership. Front Microbiol. 2022;13:877776. doi:3389/fmicb.2022.877776
  10.  Li JY, Yu M, Pal S, et al. Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota. J Clin Invest. 2020;130(4):1767-1781. doi:1172/JCI133473
  11.  Hansen MS, Frost M. Alliances of the gut and bone axis. Semin Cell Dev Biol. 2022;123:74-81. doi:1016/j.semcdb.2021.06.024
  12.  Jensen NW, Clemmensen KKB, Jensen MM, et al. Associations between postprandial gut hormones and markers of bone remodeling. Nutrients. 2021;13(9):3197. doi:3390/nu13093197
  13.  Morze J, Danielewicz A, Przybylowicz K, Zeng H, Hoffmann G, Schwingshackl L. An updated systematic review and meta-analysis on adherence to Mediterranean diet and risk of cancer. Eur J Nutr. 2021;60(3):1561-1586. doi:1007/s00394-020-02346-6
  14.  Papadaki A, Nolen-Doerr E, Mantzoros CS. The effect of the Mediterranean diet on metabolic health: a systematic review and meta-analysis of controlled trials in adults. Nutrients. 2020;12(11):3342. doi:3390/nu12113342
  15.  Noori M, Jayedi A, Khan TA, Moradi S, Shab-Bidar S. Mediterranean dietary pattern and bone mineral density: a systematic review and dose-response meta-analysis of observational studies. Eur J Clin Nutr. 2022;76(12):1657-1664. doi:1038/s41430-022-01093-7
  16.  Hughes RL, Alvarado DA, Swanson KS, Holscher HD. The prebiotic potential of inulin-type fructans: a systematic review. Adv Nutr. 2021;13(2):492-529. doi:1093/advances/nmab119
  17.  Malmir H, Ejtahed HS, Soroush AR, et al. Probiotics as a new regulator for bone health: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2021;2021:3582989. doi:1155/2021/3582989
  18.  Xu Q, Li D, Chen J, et al. Crosstalk between the gut microbiota and postmenopausal osteoporosis: mechanisms and applications. Int Immunopharmacol. 2022;110:108998. doi:1016/j.intimp.2022.108998
  19.  Feng W, Wang X, Huang D, Lu A. Role of diet in osteoporosis incidence: umbrella review of meta-analyses of prospective observational studies. Crit Rev Food Sci Nutr. 2023;63(19):3420-3429. doi:1080/10408398.2021.1989374

Source:  The Institute for Functional Medicine Newsletter – December 2023

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