The Effect of Gut Microbiota on Bone Health: Current Approaches

Yıl 2024, Sayı: 23, 983 - 992, 31.08.2024

Çağla Pınarlı , Rabia Melda Karaağaç

Öz

The incidence of osteoporosis is increasing day by day. Especially advancing age, gender, vitamin D levels are some of the risk factors. In recent years, it is thought that the gut microbiota has effects on bone health. It is known that different diseases such as hyperparathyroidism, malabsorption, hyperthyroidism, anorexia nervosa, chronic kidney failure, long-term lack of physical activity, and Cushing's syndrome may also be effective in the formation of osteoporosis. Dysbiosis in the gut microbiota is one of the factors that complicates bone healing. It seems that microbiota may play a role in bone healing and bone health through lipopolysaccharides, bile acid, short-chain fatty acids, indirect effects of microbiota on hormones, and indirect effects of microbiota on the immune system. The aim of this review is to evaluate the effects of gut microbiota on bone health with current approaches.

Anahtar Kelimeler

Microbiota, bone health, osteoporosis

Kemik Sağlığında Bağırsak Mikrobiyotasının Etkisi: Güncel Yaklaşımlar

Öz

Osteoporozun görülme sıklığı günden güne artış göstermektedir. Özellikle ilerleyen yaş, cinsiyet, D vitamini seviyeleri risk faktörlerinden bazıları olarak karşımıza çıkmaktadır. Son yıllarda ise, bağırsak mikrobiyotasının kemik sağlığı üzerinde etkileri olduğu düşünülmektedir. Osteoporozun oluşmasında hiperparatiroidizm malabsorpsiyon, hipertiroidizm, anoreksiya nervoza, kronik böbrek yetmezliği, uzun sürekli fiziksel aktivite azlığı ve Cushing sendromu gibi farklı hastalıkların da etkili olabileceği bilinmektedir. Bağırsak mikrobiyotasında disbiyoz, kemik iyileşmesini zorlaştıran faktörlerden biridir. Mikrobiyotanın kemik iyileşmesi ve kemik sağlığı üzerinde lipopolisakkaritler, safra asidi, kısa zincirli yağ asitleri, mikrobiyotanın hormonlar üzerinde olan dolaylı etkileri ve mikrobiyotanın bağışıklık sistemi üzerinde olan dolaylı etkileri aracılığıyla rol oynayabileceği görünmektedir. Bu derlemenin amacı bağırsak mikrobiyotasının kemik sağlığı üzerindeki etkilerini güncel yaklaşımlarla değerlendirilmesidir.

Anahtar Kelimeler

Mikrobiyota, kemik sağlığı, osteoporoz

Kaynakça

• 1. Prince RL, Lewis JR, Lim WH, et al. Adding lateral spine imaging for vertebral fractures to densitometric screening: ımproving ascertainment of patients at high risk of ıncident osteoporotic fractures. J Bone Miner Res. 2019;34(2):282-289.
• 2. Varacallo MA, Fox EJ. Osteoporosis and its complications. Medical Clinics of North America. 2014;98(4):817-831.
• 3. Varacallo M, Seaman TJ, Jandu JS, Pizzutillo P. Osteopenia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; October 24, 2022.
• 4. Porter JL, Varacallo M. Osteoporosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 4, 2022.
• 5. Pouresmaeili F, Kamalidehghan B, Kamarehei M, Goh YM. A comprehensive overview on osteoporosis and its risk factors. Ther Clin Risk Manag. 2018;14:2029-2049.
• 6. Bahney CS, Zondervan RL, Allison P, et al. Cellular biology of fracture healing. J Orthop Res. 2019;37(1):35-50.
• 7. Xu Z, Xie Z, Sun J, et al. Gut microbiome reveals specific dysbiosis in primary osteoporosis. Front Cell Infect Microbiol. 2020;10:160.
• 8. He J, Xu S, Zhang B, et al. Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis. Aging (Albany NY). 2020;12(9):8583-8604.
• 9. Wang J, Wang Y, Gao W, et al. Diversity analysis of gut microbiota in osteoporosis and osteopenia patients. PeerJ. 2017;5:e3450.
• 10. Lorenzo J. From the gut to bone: connecting the gut microbiota with Th17 T lymphocytes and postmenopausal osteoporosis. J Clin Invest. 2021;131(5):e146619.
• 11. Sheen JR, Garla VV. Fracture Healing Overview. StatPearls Publishing: Treasure Island, FL, USA, 2020.
• 12. Kenkre JS, Bassett J. The bone remodelling cycle. Ann Clin Biochem. 2018;55(3):308-327.
• 13. Chen X, Wang Z, Duan N, Zhu G, Schwarz EM, Xie C. Osteoblast-osteoclast interactions. Connect Tissue Res. 2018;59(2):99-107.
• 14. Castaneda M, Smith KM, Nixon JC, Hernandez CJ, Rowan S. Alterations to the gut microbiome impair bone tissue strength in aged mice. Bone Rep. 2021;14:101065.
• 15. Seely KD, Kotelko CA, Douglas H, Bealer B, Brooks AE. The human gut microbiota: A key mediator of osteoporosis and osteogenesis. International Journal of Molecular Sciences. 2021;22(17):9452.
• 16. Li L, Rao S, Cheng Y, et al. Microbial osteoporosis: The interplay between the gut microbiota and bones via host metabolism and immunity. Microbiologyopen. 2019;8(8):e00810.
• 17. Jayashree B, Bibin YS, Prabhu D, et al. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem. 2014;388(1-2):203-210.
• 18. Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. 2010;31(6):817-844.
• 19. Mohammad S, Thiemermann C. Role of metabolic endotoxemia in systemic inflammation and potential interventions. Front Immunol. 2021;11:594150.
• 20. Smith BJ, Lerner MR, Bu SY, et al. Systemic bone loss and induction of coronary vessel disease in a rat model of chronic inflammation. Bone. 2006;38(3):378-386.
• 21. Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014;30(3):332-338.
• 22. Deutschmann K, Reich M, Klindt C, et al. Bile acid receptors in the biliary tree: TGR5 in physiology and disease. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4 Pt B):1319-1325.
• 23. Kitazawa R, Mori K, Yamaguchi A, Kondo T, Kitazawa S. Modulation of mouse RANKL gene expression by Runx2 and vitamin D3. J Cell Biochem. 2008;105(5):1289-1297.
• 24. Yu L, Jia D, Feng K, et al. A natural compound (LCA) isolated from Litsea cubeba inhibits RANKL-induced osteoclast differentiation by suppressing Akt and MAPK pathways in mouse bone marrow macrophages. J Ethnopharmacol. 2020;257:112873.
• 25. McCabe L, Britton RA, Parameswaran N. Prebiotic and probiotic regulation of bone health: role of the intestine and its microbiome. Curr Osteoporos Rep. 2015;13(6):363-371.
• 26. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325-2340.
• 27. Zhang J, Motyl KJ, Irwin R, MacDougald OA, Britton RA, McCabe LR. Loss of bone and wnt10b expression in male type 1 diabetic mice is blocked by the Probiotic Lactobacillus reuteri. Endocrinology. 2015;156(9):3169-3182.
• 28. Yakar S, Rosen CJ, Beamer WG, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002;110(6):771-781.
• 29. Wang Y, Cheng Z, Elalieh HZ, et al. IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP/Ihh pathway. J Bone Miner Res. 2011;26(7):1437-1446. doi: 10.1002/jbmr.359.
• 30. Ducy P, Karsenty G. The two faces of serotonin in bone biology. Journal of Cell Biology. 2010;191:7–13.
• 31. Lam V, Su J, Koprowski S, et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012;26(4):1727-1735.
• 32. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174-180.
• 33. Ashonibare VJ, Akorede BA, Ashonibare PJ, Akhigbe TM, Akhigbe RE. Gut microbiota-gonadal axis: the impact of gut microbiota on reproductive functions. Front Immunol. 2024;15:1346035.
• 34. Ridlon JM, Ikegawa S, Alves JM, et al. Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens. J Lipid Res. 2013;54(9):2437-2449.
• 35. Xu X, Jia X, Mo L, et al. Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis. Bone Res. 2017;5:17046.
• 36. Yu M, Pal S, Paterson CW, et al. Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells. J Clin Invest. 2021;131(4):e143137.