Intestinal Microbiota and Bone Health: The Role of Prebiotics, Probiotics, and Diet

  • Fraser L. Collins
  • Soon Mi Kim
  • Laura R. McCabeEmail author
  • Connie M. WeaverEmail author
Part of the Molecular and Integrative Toxicology book series (MOLECUL)


In recent years, the intestinal microbiota has emerged as a crucial regulator of health with dysbiosis linked to a number of pathological states such as inflammatory bowel disease. In addition to a local intestinal effect, emerging evidence has demonstrated the potential for the microbiota to modulate systemic bone health via a gut-bone axis. In the present chapter, we discuss how diet can affect the composition of the intestinal microbiota, through the intake of prebiotics, and how these are utilized by the bacteria to influence the immune system and bone. In addition, we detail the recent murine studies that investigate how probiotic supplementation can increase bone mineral density in “healthy” individuals and protect against the pathological bone loss associated with menopausal estrogen deficiency. Finally, we highlight the advances made in unearthing the mechanisms that potentially lead to these observed beneficial effects.


Microbiota Probiotic Prebiotic Bone Osteoporosis 



The writing of this review and research in the author’s labsis supported by funding from the National Institutes of Health Grants: DK101050 (LRM), AT007695 (LRM) and Berries and Bones R01AT008754 (CMW).


  1. Abreu MT. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol. 2010;10(2):131–44. Available at: Scholar
  2. Alekel DL, et al. The Soy Isoflavones for Reducing Bone Loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr. 2010;91(1):218–30.PubMedCrossRefGoogle Scholar
  3. Alpan O. Oral tolerance and gut-oriented immune response to dietary proteins. Curr Allergy Asthma Rep. 2001;1(6):572–7.PubMedCrossRefGoogle Scholar
  4. Amdekar S, et al. Lactobacillus protected bone damage and maintained the antioxidant status of liver and kidney homogenates in female wistar rats. Mol Cell Biochem. 2012;368:155–65.PubMedCrossRefGoogle Scholar
  5. Andersen TL, et al. A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol. 2009;174(1):239–47. Available at: [Accessed 28 Oct 2013].PubMedPubMedCentralCrossRefGoogle Scholar
  6. Arunachalam KD. Role of bifidobacteria in nutrition, medicine and technology. Nutr Res. 1999;19(10):1559–97.CrossRefGoogle Scholar
  7. Azuma Y, et al. Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts. J Biol Chem. 2000;275(7):4858–64. Available at: Accessed 28 Oct 2013.PubMedCrossRefGoogle Scholar
  8. Bai XC, et al. Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-??B. Biochem Biophys Res Commun. 2004;314:197–207.PubMedCrossRefGoogle Scholar
  9. Beermann C, Hartung J. Physiological properties of milk ingredients released by fermentation. Food Funct. 2013;4:185–99.PubMedCrossRefGoogle Scholar
  10. Bested AC, Logan AC, Selhub EM. Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part II – contemporary contextual research. Gut Pathog. 2013;5(1):3. Available at: Accessed 16 Nov 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bismar H, et al. Increased cytokine secretion by human bone marrow cells after menopause or discontinuation of estrogen replacement. J Clin Endocrinol Metab. 1995;80(11):3351–5. Available at: Accessed 20 Nov 2013.PubMedGoogle Scholar
  12. Bonaz BL, Bernstein CN. Brain-gut interactions in inflammatory bowel disease. Gastroenterology. 2013;144(1):36–49.PubMedCrossRefGoogle Scholar
  13. Bonewald LF, Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone. 2008;42(4):606–15. Available at: Accessed 31 Oct 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Britton RA, et al. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol. 2014;229(11):1822–30. Available at” Accessed 29 Dec 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bucay N, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 1998;12(9):1260–8. Available at: Accessed 31 Oct 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Campbell JM, Fahey GC, Wolf BW. Selected indigestible oligosaccharides affect large bowel mass, cecal and fecal short-chain fatty acids, pH and microflora in rats. J Nutr. 1997;127:130–6.PubMedGoogle Scholar
  17. Caplice E, Fitzgerald GF. Food fermentations: role of microorganisms in food production and preservation. Int J Food Microbiol. 1999;50(1–2):131–49.PubMedCrossRefGoogle Scholar
  18. Cappuccio FP, et al. High blood pressure and bone-mineral loss in elderly white women: a prospective study. Study of Osteoporotic Fractures Research Group. Lancet. 1999;354(9183):971–5.PubMedCrossRefGoogle Scholar
  19. Cassidy A. Factors affecting the bioavailability of soy isoflavones in humans. J AOAC Int. 2006;89(4):1182–8.PubMedGoogle Scholar
  20. Chandran P, et al. Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (I). Surg J R Coll Surg Edinb Irel. 2003;1(2):63–75.Google Scholar
  21. Chen TR, Su RQ, Wei QK. Hydrolysis of isoflavone phytoestrogens in soymilk fermented by lactobacillus and bifidobacterium cocultures. J Food Biochem. 2010;34(1):1–12.CrossRefGoogle Scholar
  22. Chen JR, et al. Soy protein isolates prevent loss of bone quantity associated with obesity in rats through regulation of insulin signaling in osteoblasts. FASEB J. 2013;27(9):3514–23.PubMedCrossRefGoogle Scholar
  23. Cheung ALTF, et al. Fermentation of calcium-fortified soya milk does not appear to enhance acute calcium absorption in osteopenic post-menopausal women. Br J Nutr. 2011;105(2):282–6.PubMedCrossRefGoogle Scholar
  24. Chiang SS, Pan TM. Antiosteoporotic effects of lactobacillus-fermented soy skim milk on bone mineral density and the microstructure of femoral bone in ovariectomized mice. J Agric Food Chem. 2011;59:7734–42.PubMedCrossRefGoogle Scholar
  25. Chiang SS, Pan TM. Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health. Appl Microbiol Biotechnol. 2013;97(4):1489–500.PubMedCrossRefGoogle Scholar
  26. Claesson MJ, et al. Gut microbiota composition correlates with diet and health in the elderly. 2012. Available at: Scholar
  27. Clemens TL, Karsenty G. The osteoblast: an insulin target cell controlling glucose homeostasis. J Bone Miner Res. 2011;26(4):677–80.PubMedCrossRefGoogle Scholar
  28. Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol. 2008;79(8 Suppl):1569–76.PubMedCrossRefGoogle Scholar
  29. Cook SI, Sellin JH. Review article: short chain fatty acids in health and disease. Aliment Pharmacol Ther. 1998;12(6):499–507.PubMedCrossRefGoogle Scholar
  30. Costabile A, et al. Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study. Br J Nutr. 2008;99(1):110–20.PubMedCrossRefGoogle Scholar
  31. Cotillard A, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585–8. Available at: Scholar
  32. Crittenden RG, Martinez NR, Playne MJ. Synthesis and utilisation of folate by yoghurt starter cultures and probiotic bacteria. Int J Food Microbiol. 2003;80:217–22.PubMedCrossRefGoogle Scholar
  33. Cummings JH, et al. The effect of meat protein and dietary fiber on colonic function and metabolism. II. Bacterial metabolites in feces and urine. Am J Clin Nutr. 1979;32(10):2094–101.PubMedGoogle Scholar
  34. Cummings JH, et al. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28(10):1221–7.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Cuzzocrea S, et al. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice. Endocrinology. 2003;144:1098–107.PubMedCrossRefGoogle Scholar
  36. D’Amelio P, Grimaldi A, Pescarmona GP, Tamone C, Roato I, Isaia G. Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporosis. FASEB J. 2005;19(3):410–2.Google Scholar
  37. D’Amelio P, et al. Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone. 2008;43(1):92–100. Available at: Accessed 28 Oct 2013.PubMedCrossRefGoogle Scholar
  38. David LA, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63. Available at: Scholar
  39. De Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol. 2008;111:1–66. Available at: Scholar
  40. Food and Agriculture Organization of the United Nations (FAO). Report of a joint FAO/WHO working group on drafting guide- lines for the evaluation of probiotics in food. London, Ontario, Canada, 30 April–1 May 2002.
  41. Fonseca D, Ward WE. Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice. Bone. 2004;35(2):489–97.PubMedCrossRefGoogle Scholar
  42. Foureaux RDC, et al. Effects of probiotic therapy on metabolic and inflammatory parameters of rats with ligature-induced periodontitis associated with restraint stress. J Periodontol. 2013;0:1–15.Google Scholar
  43. Frankel WL, et al. Mediation of the trophic effects of short-chain fatty acids on the rat jejunum and colon. Gastroenterology. 1994;106(2):375–80.PubMedCrossRefGoogle Scholar
  44. Fujioka M, et al. Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice. J Nutr. 2004;134(10):2623–7.PubMedGoogle Scholar
  45. Ghanem KZ, Badawy IH, Abdel-Salam AM. Influence of yoghurt and probiotic yoghurt on the absorption of calcium, magnesium, iron and bone mineralization in rats. Milchwissenschaft. 2004;59(9–10):472–5. Available at: Accessed 20 Jan 2015.Google Scholar
  46. Gill SR, et al. Metagenomic analysis of the human distal gut microbiome. Science (New York, NY). 2006;312(5778):1355–9.CrossRefGoogle Scholar
  47. Gough AK, et al. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994;344(8914):23–7.PubMedCrossRefGoogle Scholar
  48. Haron H, et al. Absorption of calcium from milk and tempeh consumed by postmenopausal Malay women using the dual stable isotope technique. Int J Food Sci Nutr. 2010;61(2):125–37.PubMedCrossRefGoogle Scholar
  49. Harvey N, Dennison E, Cooper C. Osteoporosis: impact on health and economics. Nat Rev Rheumatol. 2010;6(2):99–105. Available at: Scholar
  50. Ibnou-Zekri N, et al. Divergent patterns of colonization and immune response elicited from two intestinal lactobacillus strains that display similar properties in vitro. Infect Immun. 2003;71(1):428–36. Available at: Scholar
  51. Ing-Lorenzini K, et al. Low-energy femoral fractures associated with the long-term use of bisphosphonates: a case series from a Swiss university hospital. Drug Saf Int J Med Toxicol Drug Experience. 2009;32(9):775–85.CrossRefGoogle Scholar
  52. Jilka RL, et al. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science (New York, NY). 1992;257(5066):88–91. Available at: Accessed 9 Jan 2014.CrossRefGoogle Scholar
  53. Jin LZ, et al. Probiotics in poultry: modes of action. World Poult Sci Assoc. 1997;53:351–63.CrossRefGoogle Scholar
  54. Jovanovic-Malinovska R, Kuzmanova S, Winkelhausen E. Oligosaccharide profile in fruits and vegetables as sources of prebiotics and functional foods. Int J Food Prop. 2014;17(5):949–65. Available at: Scholar
  55. Kalu DN. The ovariectomized rat model of postmenopausal bone loss. Bone Miner. 1991;15(3):175–91. Available at: Scholar
  56. Kamau SM, et al. Functional significance of bioactive peptides derived from milk proteins. Food Rev Intl. 2010;26(4):386–401.CrossRefGoogle Scholar
  57. Karsenty G, Kronenberg HM, Settembre C. Genetic control of bone formation. Annu Rev Cell Dev Biol. 2009;25:629–48. Available at: Accessed 29 Jan 2014.PubMedCrossRefGoogle Scholar
  58. Kasukawa Y, et al. Effects of risedronate alone or combined with vitamin K2on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis. J Bone Miner Metab. 2014;32(3):290–7.PubMedCrossRefGoogle Scholar
  59. Katsuyama H, et al. Promotion of bone formation by fermented soybean (Natto) intake in premenopausal women. J Nutr Sci Vitaminol. 2004;50(2):114–20.PubMedCrossRefGoogle Scholar
  60. Kelsall BL, Leon F. Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease. Immunol Rev. 2005;206:132–48.PubMedCrossRefGoogle Scholar
  61. Kendler DL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res Off J Am Soc Bone Miner Res. 2010;25(1):72–81.CrossRefGoogle Scholar
  62. Khan RU, Naz S. The applications of probiotics in poultry production. Worlds Poult Sci J. 2013;69(03):621–32. Available at: Accessed 13 Jan 2015.CrossRefGoogle Scholar
  63. Kim DW, et al. Soy isoflavones mitigate long-term femoral and lumbar vertebral bone loss in middle-aged ovariectomized mice. J Med Food. 2009a;12(3):536–41.PubMedCrossRefGoogle Scholar
  64. Kim JG, et al. Effects of a Lactobacillus casei 393 fermented milk product on bone metabolism in ovariectomised rats. Int Dairy J. 2009b;19(11):690–5. Available at: Scholar
  65. Kobayashi K, et al. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191(2):275–86. Available at: Accessed 29 Jan 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Kruger MC, et al. The effect of Lactobacillus rhamnosus HN001 on mineral absorption and bone health in growing male and ovariectomised female rats. Dairy Sci Technol. 2009;89:219–31.CrossRefGoogle Scholar
  67. Le Chatelier E, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–6. Available at: Scholar
  68. Lee YS, Noguchi T, Naito H. Phosphopeptides and soluble calcium in the small intestine of rats given a casein diet. Br J Nutr. 1980;43(3):457–67.PubMedCrossRefGoogle Scholar
  69. Legette LL, et al. Supplemental dietary racemic equol has modest benefits to bone but has mild uterotropic activity in ovariectomized rats. J Nutr. 2009;139(10):1908–13.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Lorenzo J, Horowitz M, Choi Y. Osteoimmunology: interactions of the bone and immune system. Endocr Rev. 2008;29(4):403–40.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Macfarlane GT, Steed H, Macfarlane S. Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics. J Appl Microbiol. 2008;104(2):305–44.PubMedGoogle Scholar
  72. Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010;31:266–300.PubMedPubMedCentralCrossRefGoogle Scholar
  73. McCabe LR, et al. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice. J Cell Physiol. 2013;228(8):1793–8. Available at: Accessed 6 Nov 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Messora MR, et al. Probiotic therapy reduces periodontal tissue destruction and improves the intestinal morphology in rats with ligature-induced periodontitis. J Periodontol. 2013;84:1818–26. Available at: Scholar
  75. Metchnikoff E. Essais optimistes. In: The prolongation of life. Optimistic studies. Translated and edited by P. Chalmers Mitchell. London: Heinemann; 1907.Google Scholar
  76. Mutuş R, et al. The effect of dietary probiotic supplementation on tibial bone characteristics and strength in broilers. Poult Sci. 2006;85(9):1621–5. Available at: Accessed 6 Jan 2015.PubMedGoogle Scholar
  77. Nagpal R, et al. Bioactive peptides derived from milk proteins and their health beneficial potentials: an update. Food Funct. 2011;2(1):18–27.PubMedCrossRefGoogle Scholar
  78. Nahashon SN, Nakaue HS, Mirosh LW. Production variables and nutrient retention in single comb White Leghorn laying pullets fed diets supplemented with direct-fed microbials. Poult Sci. 1994;73(11):1699–711. Available at: Accessed 12 Jan 2015.PubMedCrossRefGoogle Scholar
  79. Nam YD, et al. Comparative analysis of korean human gut microbiota by barcoded pyrosequencing. PLoS ONE. 2011;6(7):e22109.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Narva M, Collin M, et al. Effects of long-term intervention with lactobacillus helveticus-fermented milk on bone mineral density and bone mineral content in growing rats. Ann Nutr Metab. 2004a;48:228–34.PubMedCrossRefGoogle Scholar
  81. Narva M, Halleen J, et al. Effects of Lactobacillus helveticus fermented milk on bone cells in vitro. Life Sci. 2004b;75:1727–34.PubMedCrossRefGoogle Scholar
  82. National Osteoporosis Foundation. What is osteoporosis and what causes it? [Internet]. National Osteoporosis Foundation Website. Available from:
  83. Nava GM, et al. Probiotic alternatives to reduce gastrointestinal infections: the poultry experience. Anim Health Res Rev Conf Res Workers Anim Dis. 2005;6(1):105–18. Available at: Accessed 12 Jan 2015.CrossRefGoogle Scholar
  84. Ohlsson C, et al. Probiotics protect mice from ovariectomy-induced cortical bone loss. PLoS One. 2014;9(3):e92368. Available at: Accessed 18 Apr 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Oozeer R, et al. Gut health: predictive biomarkers for preventive medicine and development of functional foods. Br J Nutr. 2010;103(10):1539–44.PubMedCrossRefGoogle Scholar
  86. Ouwehand AC, Salminen S, Isolauri E. Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek. 2002;82(1–4):279–89. Available at: Accessed 29 Dec 2014.PubMedCrossRefGoogle Scholar
  87. Pacifici R, et al. Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Natl Acad Sci U S A. 1991;88(12):5134–8. Available at: Accessed 28 Oct 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Papapoulos SE. Bisphosphonates: how do they work? Best Pract Res Clin Endocrinol Metab. 2008;22(5):831–47. Available at: Accessed 6 Oct 2013.PubMedCrossRefGoogle Scholar
  89. Payne JM. Metabolic diseases in farm animals. London: Butterworth-Heinemann; 1977.Google Scholar
  90. Plavnik I, Scott ML. Effects of additional vitamins, minerals, or brewer’s yeast upon leg weaknesses in broiler chickens. Poult Sci. 1980;59(2):459–67. Available at: Accessed 12 Jan 2015.PubMedCrossRefGoogle Scholar
  91. Reinwald S, Weaver CM. Soy components vs. whole soy: are we betting our bones on a long shot? J Nutr. 2010;140(12):2312S–7S.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Robles Alonso V, Guarner F. Linking the gut microbiota to human health. Br J Nutr. 2013;109(Suppl):S21–6. Available at: Scholar
  93. Rodrigues FC, et al. Yacon flour and Bifidobacterium longum modulate bone health in rats. J Med Food. 2012;15(7):664–70. Available at: Accessed 6 Jan 2015.PubMedCrossRefGoogle Scholar
  94. Rosen CJ, Bilezikian JP. Clinical review 123: anabolic therapy for osteoporosis. J Clin Endocrinol Metab. 2001;86(3):957–64. Available at: Accessed 8 Nov 2013PubMedCrossRefGoogle Scholar
  95. Rovenský J, et al. The effects of Enterococcus faecium and selenium on methotrexate treatment in rat adjuvant-induced arthritis. Clin Dev Immunol. 2004;11:267–73.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Rowland IR, Wiseman H, Sanders TA, Adlercreutz H, Bowey EA. Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora. Nutr Cancer. 2000;36(1):27–32.Google Scholar
  97. Sanders ME. Probiotics: definition, sources, selection, and uses. Clin Infect Dis Off Publ Infect Dis Soc Am. 2008;46(Suppl 2):S58–S61; discussion S144–51. Available at: Accessed 29 Dec 2014.
  98. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126(6):1620–33. Available at: Accessed 24 Nov 2014.PubMedCrossRefGoogle Scholar
  99. Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol. 1977;31:107–33.PubMedCrossRefGoogle Scholar
  100. Schwarz EM, Ritchlin CT. Clinical development of anti-RANKL therapy. Arthritis Res Ther. 2007;6:S7. Available at: Accessed 6 Oct 2013.CrossRefGoogle Scholar
  101. Shannon J, et al. Bisphosphonates and osteonecrosis of the jaw. J Am Geriatr Soc. 2011;59:2350–5.PubMedCrossRefGoogle Scholar
  102. Sjögren K, et al. The gut microbiota regulates bone mass in mice. J Bone Miner Res. 2012;27(6):1357–67.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Steer TE, et al. Metabolism of the soybean isoflavone glycoside genistin in vitro by human gut bacteria and the effect of prebiotics. Br J Nutr. 2003;90(3):635–42.PubMedCrossRefGoogle Scholar
  104. Suda N, et al. Participation of oxidative stress in the process of osteoclast differentiation. Biochim Biophys Acta. 1993;1157:318–23.PubMedCrossRefGoogle Scholar
  105. Sullivan TW. Skeletal problems in poultry: estimated annual cost and descriptions. Poult Sci. 1994;73(6):879–82. Available at: Accessed 6 Jan 2015.PubMedCrossRefGoogle Scholar
  106. Teitelbaum SL. Osteoclasts: what do they do and how do they do it? Am J Pathol. 2007;170(2):427–35. Available at: Accessed 28 Oct 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Tenorio MD, et al. Soybean whey enhance mineral balance and caecal fermentation in rats. Eur J Nutr. 2010;49(3):155–63.PubMedCrossRefGoogle Scholar
  108. Theill LE, Boyle WJ, Penninger JM. RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol. 2002;20:795–823.PubMedCrossRefGoogle Scholar
  109. Thomas CM, et al. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One. 2012;7(2):e31951. Available at: Accessed 6 Nov 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Tissier H. Traitement des infections intestinales par la méthode de la flore bactérienne de l’intestin. CR Soc Biol. 1906;60:359–61.Google Scholar
  111. Tomofuji T, et al. Supplementation of broccoli or Bifidobacterium longum-fermented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet. Nutr Res. 2012;32(4):301–7. Available at: Scholar
  112. Trompette A, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014;20(2):159–66. Available at: Scholar
  113. U.S. Department of Health and Human Services. Bone health and osteoporosis: a report of the surgeon general. Rockville: U.S. Department of Health and Human Services/Office of the Surgeon General; 2004.Google Scholar
  114. Villegas R, et al. Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai Women’s Health Study. Am J Clin Nutr. 2008;87(1):162–7.PubMedPubMedCentralGoogle Scholar
  115. Weaver CM, Legette LL. Equol, via dietary sources or intestinal production, may ameliorate estrogen deficiency-induced bone loss. J Nutr. 2010;140(7):1377S–9S.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Weaver CM, et al. Galactooligosaccharides improve mineral absorption and bone properties in growing rats through gut fermentation. J Agric Food Chem. 2011;59(12):6501–10.PubMedCrossRefGoogle Scholar
  117. Weaver CM, et al. Flavonoid intake and bone health. J Nutr Gerontol Geriatr. 2012;31(3):239–53.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Whisner CM, et al. Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial. Br J Nutr. 2013;110(7):1292–303. Available at: Scholar
  119. Whisner CM, et al. 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. 2014;112(3):446–56. Available at: Scholar
  120. Wu AH, et al. Soy intake and risk of breast cancer in Asians and Asian Americans. Am J Clin Nutr. 1998;68(6 Suppl):1437S–43S.PubMedGoogle Scholar
  121. Wu GD, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Yan L, Spitznagel EL. Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr. 2009;89(4):1155–63.PubMedCrossRefGoogle Scholar
  123. Yasui T, et al. Epigenetic regulation of osteoclast differentiation. Ann N Y Acad Sci. 2011;1240(1):7–13.PubMedCrossRefGoogle Scholar
  124. Yatsunenko T, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–7.PubMedPubMedCentralGoogle Scholar
  125. Yun TJ, et al. OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol. 1998;161(11):6113–21.PubMedGoogle Scholar
  126. Zhang X, et al. Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr. 2003;133(9):2874–8.PubMedGoogle Scholar
  127. Zhang X, et al. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med. 2005;165(16):1890–5.PubMedCrossRefGoogle Scholar
  128. Zhao Y, Martin BR, Weaver CM. Calcium bioavailability of calcium carbonate fortified soymilk is equivalent to cow’s milk in young women. J Nutr. 2005;135(10):2379–82.Google Scholar

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of PhysiologyMichigan State UniversityEast LansingUSA
  2. 2.Department of Food and NutritionGachon UniversitySeongnamSouth Korea
  3. 3.Department of RadiologyMichigan State UniversityEast LansingUSA
  4. 4.Biomedical Imaging Research CenterMichigan State UniversityEast LansingUSA
  5. 5.Department of Food and NutritionPurdue UniversityWest LayfayetteUSA

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