Bone metabolism and gut microbiota

doi:10.3969/j.issn.2095-4344.2015.42.021

Abstract

Abstract:

BACKGROUND: The gut microbiota in our intestine performs numerous useful functions and has a major impact on the host’s health. Recently some studies have revealed that the gut microbiota cannot only control intestinal activity but also affect bone metabolism by regulating the immune system.

OBJECTIVE: To review the new research development in the effects of gut microbiota on bone metabolism.

METHODS: We retrieved the PubMed database using “gut microbiota, immune system, bone metabolism, osteoporosis” as keywords. A total of 46 articles were included which were related to gut microbiota, immune system and bone metabolism. For the articles in the same field, those published recently or in authorized journals were selected.

RESULTS AND CONCLUSION: Gut microbiota-osteoporosis research will bridge the gaps between bone physiology, gastroenterology, immunology, and microbiology. In vivo experiments in the germ-free mice and human body have found that the gut microbiota has important effects on bone metabolism, and the intervention of antibiotics, probiotics and prebiotics has further confirmed the effects of gut microbiota on bone mass. The gut microbiota has more obvious effects on bone mass in the adolescent and post-menopause periods.
中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Bacteria, Lower Gastrointestinal Tract, Metabolism, Bone Density, Osteoporosis, Immunity, Tissue Engineering

Yuan Si-yuan, He Fang, Sheng Tong, Ishimi Yoshiko, Wang Xin-xiang. Bone metabolism and gut microbiota[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(42): 6838-6842.

Figures/Tables 1

References

[1] Sambrook P,Cooper C. Osteoporosis. Lancet.2006;367: 2010-2018.
[2] Ralston SH,Uitterlinden AG. Genetics of osteoporosis. Endocr Rev. 2010;31:629-662.
[3] Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464: 59-65.
[4] Antonopoulos DA, Huse SM, Morrison HG, et al.Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect Immun. 2009;77(6): 2367-2375.
[5] Dethlefsen L,Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A. 2011;108 Suppl 1: 4554-4561.
[6] Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. et al. Human nutrition, the gut microbiome and the immune system. Nature.2011;474:327-336.
[7] Blumberg R,Powrie F. Microbiota, disease, and back to health: a metastable journey. Sci Transl Med. 2012;4(137):137rv7.
[8] Tremaroli V,Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature.2012;489:242-249.
[9] Maynard CL, Elson CO, Hatton RD, et al.Reciprocal interactions of the intestinal microbiota and immune system. Nature.2012;489:231-241.
[10] Brzozowska MM, Sainsbury A, Eisman JA, et al. Bariatric surgery, bone loss, obesity and possible mechanisms. Obes Rev. 2013;14:52-67.
[11] Schmidt S, Mellström D, Norjavaara E, et al. Longitudinal assessment of bone mineral density in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2012;55(5):511-518.
[12] Koenig JE, Spor A, Scalfone N, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl. Acad. Sci. U.S.A. 2011;108 (Suppl. 1):4578-4585.
[13] Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222-227.
[14] Lahti L, Salojärvi J, Salonen A, et al. Tipping elements in the human intestinal ecosystem. Nat Commun. 2014;5:4344.
[15] Biagi E, Nylund L, Candela M, et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010;5(5):e10667.
[16] Claesson MJ, Cusack S, O'Sullivan O, et al.Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U.S.A. 2011,108 (Suppl. 1): 4586-4591.
[17] Cho I, Yamanishi S, Cox L, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature.2012; 488: 621-626.
[18] Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell.2014;158:705-721.

[19] Macpherson AJ,Harris NL. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol. 2004;4:478-485.
[20] Willing B, Halfvarson J, Dicksved J, et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn’s disease. Inflamm. Bowel Dis. 2009; 15:653-660.
[21] Sokol H, Pigneur B, Watterlot L, et al.Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci. U.S.A. 2008;105:16731-16736.
[22] Andoh A, Kuzuoka H, Tsujikawa T,et al. Multicenter analysis of fecal microbiota profiles in Japanese patients with Crohn’s disease. J Gastroenterol. 2012; 47:1298-1307.
[23] Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008; 29:155-192.
[24] Lorenzo J, Horowitz M, Choi Y.. Osteoimmunology: interactions of the bone and immune system. Endocr. 2008; 29:403-440.
[25] Kong YY, Feige U, Sarosi I, et al.Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature.1999; 402:304-309.
[26] Martin-Millan M, Almeida M, Ambrogini E, et al. The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol. 2010;24: 323-334.
[27] Nakamura T, Imai Y, Matsumoto T, et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell.2007;130, 811-823.
[28] Pasco JA, Kotowicz MA, Henry MJ, et al. High-sensitivity C-reactive protein and fracture risk in elderly women. JAMA.2006;296:1353-1355.
[29] Ding C, Parameswaran V, Udayan R, et al. Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab. 2008;93:1952-1958.
[30] Schett G, Kiechl S, Weger S, et al. High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med.2006;166:2495-2501.
[31] Eriksson AL, Movérare-Skrtic S, Ljunggren Ö, et al. High-sensitivity CRP is an independent risk factor for all fractures and vertebral fractures in elderly men: the MrOS Sweden study. J Bone Miner Res. 2014;29:418-423.
[32] Charatcharoenwitthaya N, Khosla S, Atkinson EJ, et al. Effect of blockade of TNF- alpha and interleukin-1 action on bone resorption in early postmenopausal women. J Bone Miner Res. 2007;22:724-729.
[33] Li JY, Tawfeek H, Bedi B, et al. Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand. Proc Natl Acad Sci.U.S.A. 2011;108: 768-773.
[34] Roggia C, Gao Y, Cenci S, et al. Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc. Natl. Acad. Sci. U.S.A. 2001;98:13960-13965.
[35] Sjögren K, Engdahl C, Henning P, et al. The gut microbiota regulates bone mass in mice. J Bone Miner Res. 2012;27: 1357-1367.
[36] Li, JY. Gut microbiota plays a pivotal role in the bone loss induced by sex steroid deficiency. J Bone Miner Res. 2014;29 (Suppl.1):1029.
[37] Williams S, Wakisaka A, Zeng QQ, et al. Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats. Bone.1996;19:637-644.
[38] Pytlik M, Folwarczna J, Janiec W.Effects of doxycycline on mechanical properties of bones in rats with ovariectomy-induced osteopenia. Calcif Tissue Int. 2004;75: 225-230.
[39] Sanders ME, Guarner F, Guerrant R,et al.An update on the use and investigation of probiotics in health and disease. Gut.2013;62:787-796.
[40] Mutu? R, Kocabagli N, Alp M, et al.The effect of dietary probiotic supplementation on tibial bone characteristics and strength in broilers.Poult Sci.2006;85: 1621-1625.
[41] Lavasani S, Dzhambazov B, Nouri M, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL- 10 producing regulatory T cells. PLoS ONE. PLoS One. 2010;5(2):e9009.
[42] Britton RA, Irwin R, Quach D, et al. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol. 2014;229: 1822-1830.
[43] McCabe LR, Irwin R, Schaefer L, et al. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice. J Cell Physiol. 2013;228: 1793-1798.
[44] Weaver CM, Martin BR, Nakatsu CH, et al. Galactooligosaccharides improve mineral absorption and bone properties in growing rats through gut fermentation. J Agric Food Chem. 2011;59:6501-6510.
[45] Whisner CM, Martin BR, Schoterman MH, et al. Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial. Br J Nutr. 2013;110:1292-1303.
[46] Abrams SA, Griffin IJ, Hawthorne KM, et al. A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr. 2005;82:471-476.