Calcified Tissue International

, Volume 102, Issue 4, pp 415–425 | Cite as

Gut Microbiota, Immune System, and Bone

Review

Abstract

The gut microbiota (GM) is the whole of commensal, symbiotic, and pathogenic microorganisms living in our intestine. The GM–host interactions contribute to the maturation of the host immune system, modulating its systemic response. It is well documented that GM can interact with non-enteral cells such as immune cells, dendritic cells, and hepatocytes, producing molecules such as short-chain fatty acids, indole derivatives, polyamines, and secondary bile acid. The receptors for some of these molecules are expressed on immune cells, and modulate the differentiation of T effector and regulatory cells: this is the reason why dysbiosis is correlated with several autoimmune, metabolic, and neurodegenerative diseases. Due to the close interplay between immune and bone cells, GM has a central role in maintaining bone health and influences bone turnover and density. GM can improve bone health also increasing calcium absorption and modulating the production of gut serotonin, a molecule that interacts with bone cells and has been suggested to act as a bone mass regulator. Thus, GM manipulation by consumption of antibiotics, changes in dietary habits, and the use of pre- and probiotics may affect bone health. This review summarizes evidences on the influence of GM on immune system and on bone turnover and density and how GM manipulation may influence bone health.

Keywords

Osteoporosis Gut microbiota Bone Immune system Probiotics Inflammation 

Notes

Funding

F. Sassi is supported by a Grant from MIUR PRIN 2015.

References

  1. 1.
    Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214. doi: 10.1038/nature11234 CrossRefGoogle Scholar
  2. 2.
    Schroeder BO, Bäckhed F (2016) Signals from the gut microbiota to distant organs in physiology and disease. Nat Med 22:1079–1089. doi: 10.1038/nm.4185 PubMedCrossRefGoogle Scholar
  3. 3.
    Le Chatelier E, Nielsen T, Qin J et al (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500:541–546. doi: 10.1038/nature12506 PubMedCrossRefGoogle Scholar
  4. 4.
    Statovci D, Aguilera M, MacSharry J, Melgar S (2017) The impact of western diet and nutrients on the microbiota and immune response at mucosal interfaces. Front Immunol 8:838. doi: 10.3389/fimmu.2017.00838 PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Sokol H, Jegou S, McQuitty C et al (2017) Specificities of the intestinal microbiota in patients with inflammatory bowel disease and Clostridium difficile infection. Gut Microbes. doi: 10.1080/19490976.2017.1361092 Google Scholar
  6. 6.
    Crovesy L, Ostrowski M, Ferreira DMTP, Rosado EL, Soares-Mota M (2017) Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials. Int J Obes. doi: 10.1038/ijo.2017.161 Google Scholar
  7. 7.
    Arumugam M, Raes J, Pelletier E et al (2011) Enterotypes of the human gut microbiome. Nature 473:174–180. doi: 10.1038/nature09944 PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Peterson CT, Sharma V, Elmén L, Peterson SN (2015) Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clin Exp Immunol 179:363–377. doi: 10.1111/cei.12474 PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Belkaid Y, Hand TW (2014) Role of the microbiota in immunity and inflammation. Cell 157:121–141. doi: 10.1016/j.cell.2014.03.011 PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Wu HJ, Wu E (2012) The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 3:4–14. doi: 10.4161/gmic.19320 PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Bauer H, Horowitz RE, Levenson SM, Popper H (1963) The response of the lymphatic tissue to the microbial flora. Studies on germfree mice. Am J Pathol 42:471–483PubMedPubMedCentralGoogle Scholar
  12. 12.
    Hamada H, Hiroi T, Nishiyama Y et al (2002) Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol 168:57–64PubMedCrossRefGoogle Scholar
  13. 13.
    Macpherson AJ, Hunziker L, McCoy K, Lamarre A (2001) IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect 3:1021–1035PubMedCrossRefGoogle Scholar
  14. 14.
    Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:107–118. doi: 10.1016/j.cell.2005.05.007 PubMedCrossRefGoogle Scholar
  15. 15.
    Smith K, McCoy KD, Macpherson AJ (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19:59–69. doi: 10.1016/j.smim.2006.10.002 PubMedCrossRefGoogle Scholar
  16. 16.
    TalhamGL, Jiang HQ, Bos NA, Cebra JJ (1999) Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system. Infect Immun 67:1992–2000Google Scholar
  17. 17.
    Bouskra D, Brézillon C, Bérard M et al (2008) Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456:507–510. doi: 10.1038/nature07450 PubMedCrossRefGoogle Scholar
  18. 18.
    Ohnmacht C, Marques R, Presley L, Sawa S, Lochner M, Eberl G (2011) Intestinal microbiota, evolution of the immune system and the bad reputation of pro-inflammatory immunity. Cell Microbiol 13:653–659. doi: 10.1111/j.1462-5822.2011.01577.x PubMedCrossRefGoogle Scholar
  19. 19.
    Wu HJ, Ivanov II, Darce J et al (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32:815–827. doi: 10.1016/j.immuni.2010.06.001 PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Scher JU, Sczesnak A, Longman RS et al (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2:e01202. doi: 10.7554/eLife.01202 PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Maeda Y, Kurakawa T, Umemoto E et al (2016) Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol 68:2646–2661. doi: 10.1002/art.39783 PubMedCrossRefGoogle Scholar
  22. 22.
    Marietta EV, Murray JA, Luckey DH et al (2016) Suppression of inflammatory arthritis by human gut-derived Prevotella histicola in humanized mice. Arthritis Rheumatol 68:2878–2888. doi: 10.1002/art.39785 PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Atarashi K, Tanoue T, Shima T et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341. doi: 10.1126/science.1198469 PubMedCrossRefGoogle Scholar
  24. 24.
    Gaboriau-Routhiau V, Rakotobe S, Lécuyer E et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31:677–689. doi: 10.1016/j.immuni.2009.08.020 PubMedCrossRefGoogle Scholar
  25. 25.
    Wu X, He B, Liu J et al (2016) Molecular insight into gut microbiota and rheumatoid arthritis. Int J MolSci 17:431. doi: 10.3390/ijms17030431 CrossRefGoogle Scholar
  26. 26.
    Lee N, Kim WU (2017) Microbiota in T-cell homeostasis and inflammatory diseases. Exp Mol Med 49:e340. doi: 10.1038/emm.2017.36 PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Ferreira CM, Vieira AT, Vinolo MA, Oliveira FA, Curi R, Martins Fdos S (2014) The central role of the gut microbiota in chronic inflammatory diseases. J Immunol Res 2014:689492. doi: 10.1155/2014/689492 PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Furusawa Y, Obata Y, Fukuda S et al (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–450. doi: 10.1038/nature12721 PubMedCrossRefGoogle Scholar
  29. 29.
    Smith PM, Howitt MR, Panikov N et al (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–573. doi: 10.1126/science.1241165 PubMedCrossRefGoogle Scholar
  30. 30.
    Brown AJ, Goldsworthy SM, Barnes AA et al (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278:11312–11319. doi: 10.1074/jbc.M211609200 PubMedCrossRefGoogle Scholar
  31. 31.
    Le Poul E, Loison C, Struyf S et al (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 278:25481–25489. doi: 10.1074/jbc.M301403200 PubMedCrossRefGoogle Scholar
  32. 32.
    Nilsson NE, Kotarsky K, Owman C, Olde B (2003) Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun 303:1047–1052PubMedCrossRefGoogle Scholar
  33. 33.
    Thangaraju M, Cresci GA, Liu K et al (2009) GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res 69:2826–2832. doi: 10.1158/0008-5472.CAN-08-4466 PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Singh N, Gurav A, Sivaprakasam S et al (2014) Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40:128–139. doi: 10.1016/j.immuni.2013.12.007 PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Arpaia N, Campbell C, Fan X et al (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504:451–455. doi: 10.1038/nature12726 PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Davie JR (2003) Inhibition of histone deacetylase activity by butyrate. J Nutr 133:2485S–2493SPubMedCrossRefGoogle Scholar
  37. 37.
    Thangaraju M, Carswell KN, Prasad PD, Ganapathy V (2009) Colon cancer cells maintain low levels of pyruvate to avoid cell death caused by inhibition of HDAC1/HDAC3. Biochem J 417:379–389. doi: 10.1042/BJ20081132 PubMedCrossRefGoogle Scholar
  38. 38.
    Sanford JA, Zhang LJ, Williams MR, Gangoiti JA, Huang CM, Gallo RL (2016) Inhibition of HDAC8 and HDAC9 by microbial short-chain fatty acids breaks immune tolerance of the epidermis to TLR ligands. Sci Immunol 1:eaah4609. doi: 10.1126/sciimmunol.aah4609 PubMedCrossRefGoogle Scholar
  39. 39.
    Huang J, Wang L, Dahiya S et al (2017) Histone/protein deacetylase 11 targeting promotes Foxp3+ Treg function. Sci Rep 7:8626. doi: 10.1038/s41598-017-09211-3 PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Park J, Kim M, Kang SG et al (2015) Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol 8:80–93. doi: 10.1038/mi.2014.44 PubMedCrossRefGoogle Scholar
  41. 41.
    Liu L, Li L, Min J et al (2012) Butyrate interferes with the differentiation and function of human monocyte-derived dendritic cells. Cell Immunol 277:6673. doi: 10.1016/j.cellimm.2012.05.011 CrossRefGoogle Scholar
  42. 42.
    Millard AL, Mertes PM, Ittelet D, Villard F, Jeannesson P, Bernard J (2002) Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages. Clin Exp Immunol 130:245–255PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Singh N, Thangaraju M, Prasad PD et al (2010) Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J Biol Chem 285:27601–27608. doi: 10.1074/jbc.M110.102947 PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Wang B, Morinobu A, Horiuchi M, Liu J, Kumagai S (2008) Butyrate inhibits functional differentiation of human monocyte-derived dendritic cells. Cell Immunol 253:54–58. doi: 10.1016/j.cellimm.2008.04.016 PubMedCrossRefGoogle Scholar
  45. 45.
    Trompette A, Gollwitzer ES, Yadava K et al (2014) Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20:159–166. doi: 10.1038/nm.3444 PubMedCrossRefGoogle Scholar
  46. 46.
    Postler TS, Ghosh S (2017) Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metab 26:110–130. doi: 10.1016/j.cmet.2017.05.008 PubMedCrossRefGoogle Scholar
  47. 47.
    Round JL, Lee SM, Li J et al (2011) The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332:974–977. doi: 10.1126/science.1206095 PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Ivanov II, Atarashi K, Manel N et al (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–498. doi: 10.1016/j.cell.2009.09.033 PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Kim M, Qie Y, Park J, Kim CH (2016) Gut microbial metabolites fuel host antibody responses. Cell Host Microbe 20:202–214. doi: 10.1016/j.chom.2016.07.001 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Longman RS, Yang Y, Diehl GE, Kim SV, Littman DR (2013) Microbiota: host interactions in mucosal homeostasis and systemic autoimmunity. Cold Spring Harb Symp Quant Biol 78:193–201. doi: 10.1101/sqb.2013.78.020081 PubMedCrossRefGoogle Scholar
  51. 51.
    Lane ER, Zisman TL, Suskind DL (2017) The microbiota in inflammatory bowel disease: current and therapeutic insights. J Inflamm Res 10:63–73. doi: 10.2147/JIR.S116088 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Maeda Y, Takeda K (2017) Role of gut microbiota in rheumatoid arthritis. J Clin Med 6:60. doi: 10.3390/jcm6060060 PubMedCentralCrossRefGoogle Scholar
  53. 53.
    Wen L, Ley RE, Volchkov PY et al (2008) Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455:1109–1113. doi: 10.1038/nature07336 PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Shukla SD, Budden KF, Neal R, Hansbro PM (2017) Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunol 6:e133. doi: 10.1038/cti.2017.6 CrossRefGoogle Scholar
  55. 55.
    Hernlund E, Svedbom A, Ivergård M et al (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136. doi: 10.1007/s11657-013-0136-1 PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Mori G, D’Amelio P, Faccio R, Brunetti G (2015) Bone-immune cell crosstalk: bone diseases. J Immunol Res 2015:108451. doi: 10.1155/2015/108451 PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    D’Amelio P, Grimaldi A, Di Bella S et al (2008) Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone 43:92–100. doi: 10.1016/j.bone.2008.02.017 PubMedCrossRefGoogle Scholar
  58. 58.
    Schwarzer M, Makki K, Storelli G et al (2016) Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science 351:854–857. doi: 10.1126/science.aad8588 PubMedCrossRefGoogle Scholar
  59. 59.
    Yan J, Herzog JW, Tsang K et al (2016) Gut microbiota induce IGF-1 and promote bone formation and growth. Proc Natl Acad Sci USA 113:E7554–E7563. doi: 10.1073/pnas.1607235113 PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Cho I, Yamanishi S, Cox L et al (2012) Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488:621–626. doi: 10.1038/nature11400 PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Cox LM, Yamanishi S, Sohn J et al (2014) Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158:705–721. doi: 10.1016/j.cell.2014.05.052 PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Nobel YR, Cox LM, Kirigin FF et al (2015) Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment. Nat Commun 6:7486. doi: 10.1038/ncomms8486 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Pytlik M, Folwarczna J, Janiec W (2004) Effects of doxycycline on mechanical properties of bones in rats with ovariectomy-induced osteopenia. Calcif Tissue Int 75:225–230. doi: 10.1007/s00223-004-0097-x PubMedCrossRefGoogle Scholar
  64. 64.
    Guss JD, Horsfield MW, Fontenele FF et al (2017) Alterations to the gut microbiome impair bone strength and tissue material properties. J Bone Miner Res 32:1343–1353. doi: 10.1002/jbmr.3114 PubMedCrossRefGoogle Scholar
  65. 65.
    Sjögren K, Engdahl C, Henning P et al (2012) The gut microbiota regulates bone mass in mice. J Bone Miner Res 27:1357–1367. doi: 10.1002/jbmr.1588 PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Ohlsson C, Nigro G, Boneca IG, Bäckhed F, Sansonetti P, Sjögren K (2017) Regulation of bone mass by the gut microbiota is dependent on NOD1 and NOD2 signaling. Cell Immunol 317:55–58. doi: 10.1016/j.cellimm.2017.05.003 PubMedCrossRefGoogle Scholar
  67. 67.
    Hayashi F, Smith KD, Ozinsky A et al (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:1099–1103. doi: 10.1038/35074106 PubMedCrossRefGoogle Scholar
  68. 68.
    Cullender TC, Chassaing B, Janzon A et al (2013) Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe 14:571–581. doi: 10.1016/j.chom.2013.10.009 PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Vijay-Kumar M, Aitken JD, Carvalho FA et al (2010) Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328:228–231. doi: 10.1126/science.1179721 PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Ionova-Martin SS, Wade JM, Tang S et al (2011) Changes in cortical bone response to high-fat diet from adolescence to adulthood in mice. Osteoporos Int 22:2283–2293. doi: 10.1007/s00198-010-1432-x PubMedCrossRefGoogle Scholar
  71. 71.
    Kufer TA, Sansonetti PJ (2007) Sensing of bacteria: NOD a lonely job. Curr Opin Microbiol 10:62–69. doi: 10.1016/j.mib.2006.11.003 PubMedCrossRefGoogle Scholar
  72. 72.
    Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, Weiser JN (2010) Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med 16:228–231. doi: 10.1038/nm.2087 PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Nigro G, Rossi R, Commere PH, Jay P, Sansonetti PJ (2014) The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15:792–798. doi: 10.1016/j.chom.2014.05.003 PubMedCrossRefGoogle Scholar
  74. 74.
    Li JY, Chassaing B, Tyagi AM et al (2016) Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics. J Clin Invest 126:2049–2063. doi: 10.1172/JCI86062 PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Zeissig S, Bürgel N, Günzel D et al (2007) Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut 56:61–72. doi: 10.1136/gut.2006.094375 PubMedCrossRefGoogle Scholar
  76. 76.
    Grootjans J, Thuijls G, Verdam F, Derikx JP, Lenaerts K, Buurman WA (2010) Non-invasive assessment of barrier integrity and function of the human gut. World J GastrointestSurg 2:61–69. doi: 10.4240/wjgs.v2.i3.61 CrossRefGoogle Scholar
  77. 77.
    Wang J, Wang Y, Gao W et al (2017) Diversity analysis of gut microbiota in osteoporosis and osteopenia patients. Peer J 5:e3450. doi: 10.7717/peerj.3450 PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Jones ML, Martoni CJ, Prakash S (2013) Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post hoc analysis of a randomized controlled trial. J Clin Endocrinol Metab 98:944–2951. doi: 10.1210/jc.2012-4262 Google Scholar
  79. 79.
    Yoon SS, Sun J (2011) Probiotics, nuclear receptor signaling, and anti-inflammatory pathways. Gastroenterol Res Pract 2011:971938. doi: 10.1155/2011/971938 PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Ly NP, Litonjua A, Gold DR, Celedón JC (2011) Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol 127:1087–1094. doi: 10.1016/j.jaci.2011.02.015 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Weaver CM, Gordon CM, Janz KF et al (2016) The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int 27:1281–1386. doi: 10.1007/s00198-015-3440-3 PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    D’Amelio P, Tamone C, Pluviano F, Di Stefano M, Isaia G (2005) Effects of lifestyle and risk factors on bone mineral density in a cohort of Italian women: suggestion for a new decision rule. Calcif Tissue Int 77:72–78. doi: 10.1007/s00223-004-0253-3 PubMedCrossRefGoogle Scholar
  83. 83.
    Wallace TC, Marzorati M, Spence L, Weaver CM, Williamson PS (2017) New frontiers in fibers: innovative and emerging research on the gut microbiome and bone health. J Am Coll Nutr 36:218–222. doi: 10.1080/07315724.2016.1257961 PubMedCrossRefGoogle Scholar
  84. 84.
    Weaver CM (2015) Diet, gut microbiome, and bone health. Curr Osteoporos Rep 13:125–130. doi: 10.1007/s11914-015-0257-0 PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    U.S. Department of Health and Human Services and U.S. Departmentof Agriculture (2015) 2015–2020 Dietary Guidelines for Americans, 8th edn. Washington, DC. http://health.gov/dietaryguidelines/2015/guidelines
  86. 86.
    D’Amelio P, Panico A, Spertino E, Isaia GC (2012) Energy metabolism and the skeleton: reciprocal interplay. World J Orthop 3:190–198. doi: 10.5312/wjo.v3.i11.190 PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Reigstad CS, Salmonson CE, Rainey JF 3rd et al (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29:1395–1403. doi: 10.1096/fj.14-259598 PubMedCrossRefGoogle Scholar
  88. 88.
    Yano JM, Yu K, Donaldson GP et al (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161:264–276. doi: 10.1016/j.cell.2015.02.047 PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Yadav VK, Ryu JH, Suda N et al (2008) Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135:825–837. doi: 10.1016/j.cell.2008.09.059 PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Kode A, Mosialou I, Silva BC et al (2012) FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin. J Clin Invest 122:3490–3503. doi: 10.1172/JCI64906 PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Yadav VK, Balaji S, Suresh PS et al (2010) Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med 16:308–312. doi: 10.1038/nm.2098 PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Cui Y, Niziolek PJ, MacDonald BT et al (2011) Lrp5 functions in bone to regulate bone mass. Nat Med 17:684–691. doi: 10.1038/nm.2388 PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    De Vernejoul MC, Collet C, Chabbi-Achengli Y (2012) Serotonin: good or bad for bone. Bonekey Rep 1:120. doi: 10.1038/bonekey.2012.120 PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Ohlsson C, Engdahl C, Fåk F et al (2014) Probiotics protect mice from ovariectomy-induced cortical bone loss. PLoS ONE 9:e92368. doi: 10.1371/journal.pone.0092368 PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Britton RA, Irwin R, Quach D et al (2014) Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol 229:1822–1830. doi: 10.1002/jcp.24636 PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Parvaneh K, Ebrahimi M, Sabran MR et al (2015) Probiotics (Bifidobacterium longum) increase bone mass density and upregulate SPARC and BMP-2 genes in rats with bone loss resulting from ovariectomy. Biomed Res Int 2015:897639. doi: 10.1155/2015/897639 PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    McCabe LR, Irwin R, Schaefer L, Britton RA (2013) Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice. J Cell Physiol 228:1793–1798. doi: 10.1002/jcp.24340 PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Collins FL, Irwin R, Bierhalter H et al (2016) Lactobacillus reuteri 6475 increases bone density in intact females only under an inflammatory setting. PLoS ONE 11:e0153180. doi: 10.1371/journal.pone.0153180 PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Rozenberg S, Body JJ, Bruyère O et al (2016) Effects of dairy products consumption on health: benefits and beliefs–a commentary from the Belgian bone club and the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases. Calcif Tissue Int 98:1–17. doi: 10.1007/s00223-015-0062-x PubMedCrossRefGoogle Scholar
  100. 100.
    Matkovic V, Landoll JD, Badenhop-Stevens NE et al (2004) Nutrition influences skeletal development from childhood to adulthood: a study of hip, spine, and forearm in adolescent females. J Nutr 134:701s–705sPubMedCrossRefGoogle Scholar
  101. 101.
    Langsetmo L, Barr SI, Berger C et al (2015) Associations of protein intake and protein source with bone mineral density and fracture risk: a population-based cohort study. J Nutr Health Aging 19:861–868. doi: 10.1007/s12603-015-0544-6 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Durosier-Izart C, Biver E, Merminod F et al (2017) Peripheral skeleton bone strength is positively correlated with total and dairy protein intakes in healthy postmenopausal women. Am J Clin Nutr 105:513–525. doi: 10.3945/ajcn.116.134676 PubMedCrossRefGoogle Scholar
  103. 103.
    Radavelli-Bagatini S, Zhu K, Lewis JR, Prince RL (2014) Dairy food intake, peripheral bone structure, and muscle mass in elderly ambulatory women. J Bone Miner Res 29:1691–1700. doi: 10.1002/jbmr.2181 PubMedCrossRefGoogle Scholar
  104. 104.
    Laird E, Molloy AM, McNulty H et al (2017) Greater yogurt consumption is associated with increased bone mineral density and physical function in older adults. Osteoporos Int 28:2409–2419. doi: 10.1007/s00198-017-4049-5 PubMedCrossRefGoogle Scholar
  105. 105.
    Pazzini CA, Pereira LJ, da Silva TA et al (2017) Probiotic consumption decreases the number of osteoclasts during orthodontic movement in mice. Arch Oral Biol 79:30–34. doi: 10.1016/j.archoralbio.2017.02.017 PubMedCrossRefGoogle Scholar
  106. 106.
    Ricoldi MST, Furlaneto FAC, Oliveira LFF et al (2017) Effects of the probiotic Bifidobacterium animalis subsp. lactis on the non-surgical treatment of periodontitis. A histomorphometric, microtomographic and immunohistochemical study in rats. PLoS ONE 12:e0179946. doi: 10.1371/journal.pone.0179946 PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Kobayashi R, Kobayashi T, Sakai F, Hosoya T, Yamamoto M, Kurita-Ochiai T (2017) Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease. Sci Rep 7:545. doi: 10.1038/s41598-017-00623-9 PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Gruner D, Paris S, Schwendicke F (2016) Probiotics for managing caries and periodontitis: systematic review and meta-analysis. J Dent 48:16–25. doi: 10.1016/j.jdent.2016.03.002 PubMedCrossRefGoogle Scholar
  109. 109.
    Gohel MK, Prajapati JB, Mudgal SV et al (2016) Effect of probiotic dietary intervention on calcium and haematological parameters in geriatrics. J Clin Diagn Res 10:05–09. doi: 10.7860/JCDR/2016/18877.7627 Google Scholar
  110. 110.
    Lei M, Hua LM, Wang DW (2016) The effect of probiotic treatment on elderly patients with distal radius fracture: a prospective double-blind, placebo-controlled randomised clinical trial. Benef Microbes 7:631–637. doi: 10.3920/BM2016.0067 PubMedCrossRefGoogle Scholar
  111. 111.
    Jafarnejad S, Djafarian K, Fazeli MR, Yekaninejad MS, Rostamian A, Keshavarz SA (2017) Effects of a multispecies probiotic supplement on bone health in osteopenic postmenopausal women: a randomized, double-blind, controlled trial. J Am Coll Nutr 19:1–10. doi: 10.1080/07315724.2017.1318724 Google Scholar
  112. 112.
    Roberfroid M (2007) Prebiotics: the concept revisited. J Nutr 137:830S–837SPubMedCrossRefGoogle Scholar
  113. 113.
    Weaver CM, Martin BR, Nakatsu CH et al (2011) Galactooligosaccharides improve mineral absorption and bone properties in growing rats through gut fermentation. J Agric Food Chem 59:6501–6510. doi: 10.1021/jf2009777 PubMedCrossRefGoogle Scholar
  114. 114.
    Scholz-Ahrens KE, Schaafsma G, van den Heuvel EG, Schrezenmeir J (2001) Effects of prebiotics on mineral metabolism. Am J ClinNutr 73:459S–464SGoogle Scholar
  115. 115.
    Whisner CM, Martin BR, Schoterman MH et al (2013) Galacto-oligosaccharides increase calcium absorption and gut Bifidobacteria in young girls: a double-blind cross-over trial. Br J Nutr 110:1292–1303. doi: 10.1017/S000711451300055X PubMedCrossRefGoogle Scholar
  116. 116.
    Abrams SA, Griffin IJ, Hawthorne KM et al (2005) A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr 82:471–476PubMedCrossRefGoogle Scholar
  117. 117.
    Whisner CM, Martin BR, Nakatsu CH et al (2016) Soluble corn fiber increases calcium absorption associated with shifts in the gut microbiome: a randomized dose-response trial in free-living pubertal females. J Nutr 146:1298–1306. doi: 10.3945/jn.115.227256 PubMedCrossRefGoogle Scholar
  118. 118.
    Whisner CM, Martin BR, Nakatsu CH et al (2014) Soluble maize fibre affects short-term calcium absorption in adolescent boys and girls: a randomised controlled trial using dual stable isotopic tracers. Br J Nutr 112:446–456. doi: 10.1017/S0007114514000981 PubMedCrossRefGoogle Scholar
  119. 119.
    Bindels LB, Delzenne NM, Cani PD, Walter J (2015) Towards a more comprehensive concept for prebiotics. Nat Rev Gastroenterol Hepatol 12:303–310. doi: 10.1038/nrgastro.2015.47 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Gerontology and Bone Metabolic Diseases Section, Department of Medical ScienceUniversity of TorinoTurinItaly

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