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Erschienen in: Calcified Tissue International 4/2018

30.09.2017 | Review

Gut Microbiota, Immune System, and Bone

Erschienen in: Calcified Tissue International | Ausgabe 4/2018

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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.
Literatur
5.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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 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
11.
Zurück zum Zitat 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 42:471–483PubMedPubMedCentral 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 42:471–483PubMedPubMedCentral
12.
Zurück zum Zitat 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 168:57–64PubMedCrossRef 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 168:57–64PubMedCrossRef
13.
Zurück zum Zitat Macpherson AJ, Hunziker L, McCoy K, Lamarre A (2001) IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect 3:1021–1035PubMedCrossRef Macpherson AJ, Hunziker L, McCoy K, Lamarre A (2001) IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect 3:1021–1035PubMedCrossRef
16.
Zurück zum Zitat 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 67:1992–2000 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 67:1992–2000
21.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
30.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
31.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
32.
Zurück zum Zitat 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 303:1047–1052PubMedCrossRef 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 303:1047–1052PubMedCrossRef
36.
Zurück zum Zitat Davie JR (2003) Inhibition of histone deacetylase activity by butyrate. J Nutr 133:2485S–2493SPubMedCrossRef Davie JR (2003) Inhibition of histone deacetylase activity by butyrate. J Nutr 133:2485S–2493SPubMedCrossRef
37.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
38.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
40.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
42.
Zurück zum Zitat 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 130:245–255PubMedPubMedCentralCrossRef 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 130:245–255PubMedPubMedCentralCrossRef
43.
45.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
55.
Zurück zum Zitat 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 PubMedPubMedCentralCrossRef 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 PubMedPubMedCentralCrossRef
64.
67.
73.
75.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
76.
Zurück zum Zitat 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 CrossRef 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 CrossRef
78.
Zurück zum Zitat 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 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
81.
82.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
87.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
96.
99.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
100.
Zurück zum Zitat 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–705sPubMedCrossRef 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–705sPubMedCrossRef
102.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
103.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
104.
106.
109.
110.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
111.
Zurück zum Zitat 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 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
113.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
114.
Zurück zum Zitat Scholz-Ahrens KE, Schaafsma G, van den Heuvel EG, Schrezenmeir J (2001) Effects of prebiotics on mineral metabolism. Am J ClinNutr 73:459S–464S Scholz-Ahrens KE, Schaafsma G, van den Heuvel EG, Schrezenmeir J (2001) Effects of prebiotics on mineral metabolism. Am J ClinNutr 73:459S–464S
115.
116.
Zurück zum Zitat 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 82:471–476PubMedCrossRef 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 82:471–476PubMedCrossRef
117.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
118.
Zurück zum Zitat 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 PubMedCrossRef 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/​S000711451400098​1 PubMedCrossRef
Metadaten
Titel
Gut Microbiota, Immune System, and Bone
Publikationsdatum
30.09.2017
Erschienen in
Calcified Tissue International / Ausgabe 4/2018
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-017-0331-y

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