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Dietary factors in rheumatic autoimmune diseases: a recipe for therapy?

Key Points

  • Dietary habits have long been known to have a crucial influence on human health and diseases

  • Novel roles of dietary factors in the complex interaction of different environmental factors in the pathogenesis of rheumatic autoimmune disease, as part of the 'mosaic of autoimmunity' concept, are now increasingly appreciated

  • Whereas salt seems to promote inflammation via various mechanisms, consumption of curcumin, spicy food (capsaicin), chocolate and red wine (resveratrol) might attenuate immune hyperactivity; consumption of fatty acids and coffee seems to have ambivalent effects on autoimmunity

  • The human gut microbiome is emerging as a key contributor to and a common denominator of the effects of these dietary compounds on the immune system and the development of immune-mediated diseases

Abstract

Today, we are facing a new era of digitization in the health care system, and with increased access to health care information has come a growing demand for safe, cost-effective and easy to administer therapies. Dietary habits have a crucial influence on human health, affecting an individual's risk for hypertension, heart disease and stroke, as well as influencing the risk of developing of cancer. Moreover, an individual's lifestyle choices can greatly influence the progression and manifestation of chronic autoimmune rheumatic diseases. In light of these effects, it makes sense that the search for additional therapies to attenuate such diseases would include investigations into lifestyle modifications. When considering the complex web of factors that influence autoimmunity, it is not surprising to find that several dietary elements are involved in disease progression or prevention. In this Review, several common nutritional components of the human diet are presented, and the evidence for their effects on rheumatic diseases is discussed.

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Figure 1: Dietary factors associated with autoimmunity.
Figure 2: The role of diet in shaping the gut microbiome.
Figure 3: Molecular mechanisms linking a high-salt diet to an inflammatory response.

References

  1. Shoenfeld, Y. & Isenberg, D. A. The mosaic of autoimmunity. Immunol. Today 10, 123–126 (1989).

    CAS  PubMed  Google Scholar 

  2. Cooper, G. S., Miller, F. W. & Pandey, J. P. The role of genetic factors in autoimmune disease: implications for environmental research. Environ. Health Perspect. 107 (Suppl. 5), 693–700 (1999).

    PubMed  PubMed Central  Google Scholar 

  3. Cruz-Tapias, P. et al. Shared HLA class II in six autoimmune diseases in Latin America: a meta-analysis. Autoimmune Dis. 2012, 569728 (2012).

    PubMed  PubMed Central  Google Scholar 

  4. Versini, M. et al. Unravelling the hygiene hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications. BMC Med. 13, 81 (2015).

    PubMed  PubMed Central  Google Scholar 

  5. Lerner, A. & Matthias, T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun. Rev. 14, 479–489 (2015).

    CAS  PubMed  Google Scholar 

  6. Shapira, Y., Agmon-Levin, N. & Shoenfeld, Y. Defining and analyzing geoepidemiology and human autoimmunity. J. Autoimmun. 34, J168–J177 (2010).

    CAS  PubMed  Google Scholar 

  7. Ramos-Casals, M. et al. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases. Autoimmun. Rev. 14, 670–679 (2015).

    PubMed  Google Scholar 

  8. Agmon-Levin, N., Theodor, E., Segal, R. M. & Shoenfed, Y. Vitamin D in systemic and organ-specific autoimmune diseases. Clin. Rev. Allergy Immunol. 45, 256–266 (2013).

    CAS  PubMed  Google Scholar 

  9. Orbach, H. et al. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann. NY Acad. Sci. 1109, 385–400 (2007).

    CAS  PubMed  Google Scholar 

  10. Oren, Y. et al. Vitamin D insufficiency in a sunny environment: a demographic and seasonal analysis. Isr. Med. Assoc. J. 12, 751–756 (2010).

    PubMed  Google Scholar 

  11. Azrielant, S. & Shoenfeld, Y. Eppur si muove: vitamin D is essential in preventing and modulating SLE. Lupus 25, 563–572 (2016).

    CAS  PubMed  Google Scholar 

  12. Amital, H. et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann. Rheum. Dis. 69, 1155–1157 (2010).

    CAS  PubMed  Google Scholar 

  13. Carvalho, J. F. et al. Anti-vitamin D, vitamin D in SLE: preliminary results. Ann. NY Acad. Sci. 1109, 550–557 (2007).

    CAS  PubMed  Google Scholar 

  14. Bizzaro, G. & Shoenfeld, Y. Vitamin D: a panacea for autoimmune diseases? Can. J. Physiol. Pharmacol. 93, 395–397 (2015).

    CAS  PubMed  Google Scholar 

  15. Rosen, Y., Daich, J., Soliman, I., Brathwaite, E. & Shoenfeld, Y. Vitamin D and autoimmunity. Scand. J. Rheumatol. 45, 439–447 (2016).

    CAS  PubMed  Google Scholar 

  16. Lindqvist, P. G. et al. Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort. J. Intern. Med. 280, 375–387 (2016).

    CAS  PubMed  Google Scholar 

  17. Abnet, C. C., Corley, D. A., Freedman, N. D. & Kamangar, F. Diet and upper gastrointestinal malignancies. Gastroenterology 148, 1234–1243 (2015).

    PubMed  PubMed Central  Google Scholar 

  18. Del Gobbo, L. C., Falk, M. C., Feldman, R., Lewis, K. & Mozaffarian, D. Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials. Am. J. Clin. Nutr. 102, 1347–1356 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Jayalath, V. H. et al. Sugar-sweetened beverage consumption and incident hypertension: a systematic review and meta-analysis of prospective cohorts. Am. J. Clin. Nutr. 102, 914–921 (2015).

    CAS  PubMed  Google Scholar 

  20. Widmer, R. J., Flammer, A. J., Lerman, L. O. & Lerman, A. The Mediterranean diet, its components, and cardiovascular disease. Am. J. Med. 128, 229–238 (2015).

    PubMed  Google Scholar 

  21. Scher, J. U. & Abramson, S. B. The microbiome and rheumatoid arthritis. Nat. Rev. Rheumatol. 7, 569–578 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A. & Gordon, J. I. Host-bacterial mutualism in the human intestine. Science 307, 1915–1920 (2005).

    PubMed  Google Scholar 

  23. Rosser, E. C. & Mauri, C. A clinical update on the significance of the gut microbiota in systemic autoimmunity. J. Autoimmun. 74, 85–93 (2016).

    CAS  PubMed  Google Scholar 

  24. Ley, R. E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    CAS  PubMed  Google Scholar 

  26. Carmody, R. N. et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe 17, 72–84 (2015).

    CAS  PubMed  Google Scholar 

  27. Alkanani, A. K. et al. Alterations in intestinal microbiota correlate with susceptibility to type 1 diabetes. Diabetes 64, 3510–3520 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Castillo-Álvarez, F. & Marzo-Sola, M. E. Role of intestinal microbiota in the development of multiple sclerosis. Neurologia http://dx.doi.org/10.1016/j.nrl.2015.07.005 (in Spanish) (2015).

  29. Larmonier, C., Shehab, K. W., Ghishan, F. K. & Kiela, P. R. T lymphocyte dynamics in inflammatory bowel diseases: role of the microbiome. Biomed. Res. Int. 2015, 504638 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Consolandi, C. et al. Behçet's syndrome patients exhibit specific microbiome signature. Autoimmun. Rev. 14, 269–276 (2015).

    PubMed  Google Scholar 

  31. Hevia, A. et al. Intestinal dysbiosis associated with systemic lupus erythematosus. mBio 5, e01548–14 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. López, P. Sánchez, B., Margolles, A. & Suárez, A. Intestinal dysbiosis in systemic lupus erythematosus: cause or consequence? Curr. Opin. Rheumatol. 28, 515–522 (2016).

    PubMed  Google Scholar 

  33. Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202 (2013).

    PubMed  PubMed Central  Google Scholar 

  34. Scher, J. U. et al. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 64, 3083–3094 (2012).

    PubMed  PubMed Central  Google Scholar 

  35. Van Praet, J. T. et al. Commensal microbiota influence systemic autoimmune responses. EMBO J. 34, 466–474 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhang, X. et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 21, 895–905 (2015).

    CAS  PubMed  Google Scholar 

  37. Johnson, B. M., Gaudreau, M. C., Al-Gadban, M. M., Gudi, R. & Vasu, C. Impact of dietary deviation on disease progression and gut microbiome composition in lupus-prone SNF1 mice. Clin. Exp. Immunol. 181, 323–337 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Paun, A. & Danska, J. S. Immuno-ecology: how the microbiome regulates tolerance and autoimmunity. Curr. Opin. Immunol. 37, 34–39 (2015).

    CAS  PubMed  Google Scholar 

  39. Frommer, K. W. et al. Free fatty acids: potential proinflammatory mediators in rheumatic diseases. Ann. Rheum. Dis. 74, 303–310 (2015).

    CAS  PubMed  Google Scholar 

  40. Hsieh, C. C. & Lin, B. F. Dietary factors regulate cytokines in murine models of systemic lupus erythematosus. Autoimmun. Rev. 11, 22–27 (2011).

    CAS  PubMed  Google Scholar 

  41. Miles, E. A. & Calder, P. C. Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br. J. Nutr. 107 (Suppl 2), S171–S184 (2012).

    CAS  PubMed  Google Scholar 

  42. Trebble, T. M. et al. Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease. Am. J. Clin. Nutr. 80, 1137–1144 (2004).

    CAS  PubMed  Google Scholar 

  43. Wallace, F. A. et al. Dietary fatty acids influence the production of Th1- but not Th2-type cytokines. J. Leukoc. Biol. 69, 449–457 (2001).

    CAS  PubMed  Google Scholar 

  44. Gan, R. W. et al. Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis. Ann. Rheum. Dis. 76, 147–152 (2017).

    PubMed  Google Scholar 

  45. Di Giuseppe, D., Wallin, A., Bottai, M., Askling, J. & Wolk, A. Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women. Ann. Rheum. Dis. 73, 1949–1953 (2014).

    CAS  PubMed  Google Scholar 

  46. Galarraga, B. et al. Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology (Oxford) 47, 665–669 (2008).

    CAS  Google Scholar 

  47. Kremer, J. M. et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study. Ann. Intern. Med. 106, 497–503 (1987).

    CAS  PubMed  Google Scholar 

  48. Lau, C. S., Morley, K. D. & Belch, J. J. Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis — a double-blind placebo controlled study. Br. J. Rheumatol. 32, 982–989 (1993).

    CAS  PubMed  Google Scholar 

  49. Volker, D., Fitzgerald, P., Major, G. & Garg, M. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J. Rheumatol. 27, 2343–2346 (2000).

    CAS  PubMed  Google Scholar 

  50. James, M. J. & Cleland, L. G. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin. Arthritis Rheum. 27, 85–97 (1997).

    CAS  PubMed  Google Scholar 

  51. Lee, Y. H., Bae, S. C. & Song, G. G. Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis. Arch. Med. Res. 43, 356–362 (2012).

    CAS  PubMed  Google Scholar 

  52. Reifen, R. et al. Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus. Lupus 7, 192–197 (1998).

    CAS  PubMed  Google Scholar 

  53. Chandrasekar, B., Troyer, D. A., Venkatraman, J. T. & Fernandes, G. Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor β mRNA and protein expression. J. Autoimmun. 8, 381–393 (1995).

    CAS  PubMed  Google Scholar 

  54. Bello, K. J. et al. Omega-3 in SLE: a double-blind, placebo-controlled randomized clinical trial of endothelial dysfunction and disease activity in systemic lupus erythematosus. Rheumatol. Int. 33, 2789–2796 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Duffy, E. M. et al. The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus. J. Rheumatol. 31, 1551–1556 (2004).

    CAS  PubMed  Google Scholar 

  56. Arriens, C., Hynan, L. S., Lerman, R. H, Karp, D. R. & Mohan, C. Placebo-controlled randomized clinical trial of fish oil's impact on fatigue, quality of life, and disease activity in systemic lupus erythematosus. Nutr. J. 14, 82 (2015).

    PubMed  PubMed Central  Google Scholar 

  57. Robertson, R. C. et al. Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav. Immun. 59, 21–37 (2016).

    PubMed  Google Scholar 

  58. Kaliannan, K., Wang, B., Li, X. Y., Kim, K. J. & Kang, J. X. A host–microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci. Rep. 5, 11276 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Pusceddu, M. M. et al. N-3 polyunsaturated fatty acids (PUFAs) reverse the impact of early-life stress on the gut microbiota. PLoS ONE 10, e0139721 (2015).

    PubMed  PubMed Central  Google Scholar 

  60. Rodriguez-Carrio, J., Alperi-López, M., López, P., Ballina-García, F. J. & Suárez, A. Non-esterified fatty acids profiling in rheumatoid arthritis: associations with clinical features and Th1 response. PLoS ONE 11, e0159573 (2016).

    PubMed  PubMed Central  Google Scholar 

  61. Sundström, B., Johannson, G., Kokkonen, H., Cederholm, T. & Wållberg-Jonsson, S. Plasma phospholipid fatty acid content is related to disease activity in ankylosing spondylitis. J. Rheumatol. 39, 327–333 (2012).

    PubMed  Google Scholar 

  62. Cirillo, M., Capasso, G., Di Leo, V. A. & De Santo, N. G. A history of salt. Am. J. Nephrol. 14, 426–431 (1994).

    CAS  PubMed  Google Scholar 

  63. Zhu, S. & Qian, Y. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin. Sci. (Lond.) 122, 487–511 (2012).

    CAS  Google Scholar 

  64. Kleinewietfeld, M. et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496, 518–522 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Wu, C. et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496, 513–517 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Binger, K. J., Linker, R. A., Muller, D. N. & Kleinewietfeld, M. Sodium chloride, SGK1, and Th17 activation. Pflügers Arch. 467, 543–550 (2015).

    CAS  PubMed  Google Scholar 

  67. O'Shea, J. J. & Jones, R. G. Autoimmunity: rubbing salt in the wound. Nature 496, 437–439 (2013).

    CAS  PubMed  Google Scholar 

  68. Van der Meer, J. W. & Netea, M. G. A salty taste to autoimmunity. N. Engl. J. Med. 368, 2520–2521 (2013).

    CAS  PubMed  Google Scholar 

  69. Hernandez, A. L. et al. Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. J. Clin. Invest. 125, 4212–4222 (2015).

    PubMed  PubMed Central  Google Scholar 

  70. Kleinewietfeld, M. & Hafler, D. A. The plasticity of human Treg and Th17 cells and its role in autoimmunity. Semin. Immunol. 25, 305–312 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Hucke, S. et al. Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity. J. Autoimmun. 67, 90–101 (2016).

    CAS  PubMed  Google Scholar 

  72. Salgado, E., Bes-Rastrollo, M., de Irala, J., Carmona, L. & Gómez-Reino, J. J. High sodium intake is associated with self-reported rheumatoid arthritis: a cross sectional and case control analysis within the SUN cohort. Medicine (Baltimore) 94, e924 (2015).

    Google Scholar 

  73. Sundström, B., Johansson, I. & Rantapää-Dahlqvist, S. Interaction between dietary sodium and smoking increases the risk for rheumatoid arthritis: results from a nested case-control study. Rheumatology (Oxford) 54, 487–493 (2015).

    Google Scholar 

  74. Jiang, X. et al. High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA. Ann. Rheum. Dis. 75, 943–946 (2016).

    CAS  PubMed  Google Scholar 

  75. Li, C. et al. A gene-based analysis of variants in the serum/glucocorticoid regulated kinase (SGK) genes with blood pressure responses to sodium intake: the GenSalt Study. PLoS ONE 9, e98432 (2014).

    PubMed  PubMed Central  Google Scholar 

  76. Luca, F. et al. Adaptive variation regulates the expression of the human SGK1 gene in response to stress. PLoS Genet. 5, e1000489 (2009).

    PubMed  PubMed Central  Google Scholar 

  77. Deng, Y. et al. Some like it hot: the emerging role of spicy food (capsaicin) in autoimmune diseases. Autoimmun. Rev. 15, 451–456 (2016).

    PubMed  Google Scholar 

  78. Mortensen, J. M. & Mortensen, J. E. The power of capsaicin. J. Continu. Educ. Top. Issues 11, 8–12 (2009).

    Google Scholar 

  79. Cichewicz, R. H. & Thorpe, P. A. The antimicrobial properties of chile peppers (Capsicum species) and their uses in Mayan medicine. J. Ethnopharmacol. 52, 61–70 (1996).

    CAS  PubMed  Google Scholar 

  80. Jensen, P. G., Curtis, P. D., Dunn, J. A., Austic, R. E. & Richmond, M. E. Field evaluation of capsaicin as a rodent aversion agent for poultry feed. Pest Manag. Sci. 59, 1007–1015 (2003).

    CAS  PubMed  Google Scholar 

  81. Zhang, W. Y. & Li Wan Po, A. The effectiveness of topically applied capsaicin. A meta-analysis. Eur. J. Clin. Pharmacol. 46, 517–522 (1994).

    CAS  PubMed  Google Scholar 

  82. Derry, S., Rice, A. S., Cole, P., Tan, T. & Moore, R. A. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst. Rev. 2, CD007393 (2013).

    Google Scholar 

  83. Deal, C. L. et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin. Ther. 13, 383–395 (1991).

    CAS  PubMed  Google Scholar 

  84. McCarthy, G. M. & McCarty, D. J. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J. Rheumatol. 19, 604–607 (1992).

    CAS  PubMed  Google Scholar 

  85. Mason, L., Moore, R. A., Derry, S., Edwards, J. E. & McQuay, H. J. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 328, 991 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Aggarwal, B. B., Van Kuiken, M. E., Iyer, L. H., Harikumar, K. B. & Sung, B. Molecular targets of nutraceuticals derived from dietary spices: potential role in suppression of inflammation and tumorigenesis. Exp. Biol. Med. (Maywood) 234, 825–849 (2009).

    CAS  Google Scholar 

  87. Yoshioka, M., Doucet, E., Drapeau, V., Dionne, I. & Tremblay, A. Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods. Br. J. Nutr. 85, 203–211 (2001).

    CAS  PubMed  Google Scholar 

  88. Luo, X. J., Peng, J. & Li, Y. J. Recent advances in the study on capsaicinoids and capsinoids. Eur. J. Pharmacol. 650, 1–7 (2011).

    CAS  PubMed  Google Scholar 

  89. McCarty, M. F., DiNicolantonio, J. J. & O'Keefe, J. H. Capsaicin may have important potential for promoting vascular and metabolic health. Open Heart 2, e000262 (2015).

    PubMed  PubMed Central  Google Scholar 

  90. Nilius, B. & Appendino, G. Spices: the savory and beneficial science of pungency. Rev. Physiol. Biochem. Pharmacol. 164, 1–76 (2013).

    CAS  PubMed  Google Scholar 

  91. Sharma, S. K., Vij, A. S. & Sharma, M. Mechanisms and clinical uses of capsaicin. Eur. J. Pharmacol. 720, 55–62 (2013).

    CAS  PubMed  Google Scholar 

  92. Nevius, E., Srivastava, P. K. & Basu, S. Oral ingestion of capsaicin, the pungent component of chili pepper, enhances a discreet population of macrophages and confers protection from autoimmune diabetes. Mucosal Immunol. 5, 76–86 (2012).

    CAS  PubMed  Google Scholar 

  93. Stüve, O. & Zettl, U. Neuroinflammation of the central and peripheral nervous system: an update. Clin. Exp. Immunol. 175, 333–335 (2014).

    PubMed  PubMed Central  Google Scholar 

  94. Majhi, R. K. et al. Functional expression of TRPV channels in T cells and their implications in immune regulation. FEBS J. 282, 2661–2681 (2015).

    CAS  PubMed  Google Scholar 

  95. Basu, S. & Srivastava, P. Immunological role of neuronal receptor vanilloid receptor 1 expressed on dendritic cells. Proc. Natl Acad. Sci. USA 102, 5120–5125 (2005).

    CAS  PubMed  Google Scholar 

  96. Biró, T. et al. Characterization of functional vanilloid receptors expressed by mast cells. Blood 91, 1332–1340 (1998).

  97. Yoo, S., Lim, J. Y. & Hwang, S. W. Sensory TRP channel interactions with endogenous lipids and their biological outcomes. Molecules 19, 4708–4744 (2014).

    PubMed  PubMed Central  Google Scholar 

  98. Anichini, M. et al. Substance P in the serum of patients with rheumatoid arthritis. Rev. Rhum. Engl. Ed. 64, 18–21 (1997).

    CAS  PubMed  Google Scholar 

  99. Larsson, J., Ekblom, A., Henriksson, K., Lundeberg, T. & Theodorsson, E. Concentration of substance P, neurokinin A, calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide in synovial fluid from knee joints in patients suffering from rheumatoid arthritis. Scand. J. Rheumatol. 20, 326–335 (1991).

    CAS  PubMed  Google Scholar 

  100. Denko, C. W. & Malemud, C. J. The serum growth hormone to somatostatin ratio is skewed upward in rheumatoid arthritis patients. Front. Biosci. 9, 1660–1664 (2004).

    CAS  PubMed  Google Scholar 

  101. Ahmed, M. et al. Capsaicin effects on substance P and CGRP in rat adjuvant arthritis. Regul. Pept. 55, 85–102 (1995).

    CAS  PubMed  Google Scholar 

  102. Borbély, E. et al. Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis. Brain Behav. Immun. 45, 50–59 (2015).

    PubMed  PubMed Central  Google Scholar 

  103. Lorton, D. et al. Local application of capsaicin into the draining lymph nodes attenuates expression of adjuvant-induced arthritis. Neuroimmunomodulation 7, 115–125 (2000).

    CAS  PubMed  Google Scholar 

  104. Casanueva, B., Rodero, B., Quintial, C., Llorca, J. & González-Gay, M. A. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients. Rheumatol. Int. 33, 2665–2670 (2013).

    CAS  PubMed  Google Scholar 

  105. Billing, J. & Sherman, P. W. Antimicrobial functions of spices: why some like it hot. Q. Rev. Biol. 73, 3–49 (1998).

    CAS  PubMed  Google Scholar 

  106. Omolo, M. A. et al. Antimicrobial properties of chili peppers. J. Infect. Dis. Ther. http://dx.doi.org/10.4172/2332-0877.1000145 (2014).

  107. Jones, N. L., Shabib, S. & Sherman, P. M. Capsaicin as an inhibitor of the growth of the gastric pathogen Helicobacter pylori. FEMS Microbiol. Lett. 146, 223–227 (1997).

    CAS  PubMed  Google Scholar 

  108. Chatterjee, S. et al. Capsaicin, a potential inhibitor of cholera toxin production in Vibrio cholerae. FEMS Microbiol. Lett. 306, 54–60 (2010).

    CAS  PubMed  Google Scholar 

  109. Kalia, N. P. et al. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus. J. Antimicrob. Chemother. 67, 2401–2408 (2012).

    CAS  PubMed  Google Scholar 

  110. Zhou, Y. et al. Capsaicin inhibits Porphyromonas gingivalis growth, biofilm formation, gingivomucosal inflammatory cytokine secretion, and in vitro osteoclastogenesis. Eur. J. Clin. Microbiol. Infect. Dis. 33, 211–219 (2014).

    CAS  PubMed  Google Scholar 

  111. Scoville, W. L. Note on capsicums. J. Pharm. Sci. 1, 453–454 (1912).

    CAS  Google Scholar 

  112. Weiss, E. A. Spice Crops (CABI, 2002).

    Google Scholar 

  113. Nwokem, C. O., Agbaji, E. B., Kagbu, J. A. & Ekanem, E. J. Determination of capsaicin content and pungency level of five different peppers grown in Nigeria. NY Sci. J. 3, 17–21 (2010).

    Google Scholar 

  114. Al Othman, Z. A., Ahmed, Y. B., Habila, M. A. & Ghafar, A. A. Determination of capsaicin and dihydrocapsaicin in Capsicum fruit samples using high performance liquid chromatography. Molecules 16, 8919–8929 (2011).

    CAS  PubMed  Google Scholar 

  115. Prasad, S. & Aggarwal, B. B. in Herbal Medicine: Biomolecular and Clinical Aspects 2nd edn Ch. 13 (ed. Wachtel-Galor, S.) 263–288 (CRC Press, 2011).

    Google Scholar 

  116. Lee, H., Kim, H., Lee, G., Chung, H. S. & Bae, H. Curcumin attenuates lupus nephritis upon interaction with regulatory T cells in New Zealand Black/White mice. Br. J. Nutr. 110, 69–76 (2013).

    CAS  PubMed  Google Scholar 

  117. Mohajeri, M., Sadeghizadeh, M., Najafi, F. & Javan, M. Polymerized nano-curcumin attenuates neurological symptoms in EAE model of multiple sclerosis through down regulation of inflammatory and oxidative processes and enhancing neuroprotection and myelin repair. Neuropharmacology 99, 156–167 (2015).

    CAS  PubMed  Google Scholar 

  118. Wang, S. et al. Curcumin ameliorates experimental autoimmune myasthenia gravis by diverse immune cells. Neurosci. Lett. 626, 25–34 (2016).

    CAS  PubMed  Google Scholar 

  119. Kunnumakkara, A. B. et al. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br. J. Pharmacol. http://dx.doi.org/10.1111/bph.13621 (2016).

  120. Prasad, S., Gupta, S. C., Tyagi, A. K. & Aggarwal, B. B. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol. Adv. 32, 1053–1064 (2014).

    CAS  PubMed  Google Scholar 

  121. Chandran, B. & Goel, A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother. Res. 26, 1719–1725 (2012).

    CAS  PubMed  Google Scholar 

  122. Khajehdehi, P. et al. Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis: a randomized and placebo-controlled study. J. Ren. Nutr. 22, 50–57 (2012).

    CAS  PubMed  Google Scholar 

  123. McFadden, R. M. et al. The role of curcumin in modulating colonic microbiota during colitis and colon cancer prevention. Inflamm. Bowel Dis. 21, 2483–2494 (2015).

    PubMed  PubMed Central  Google Scholar 

  124. Nelson, K. M. et al. The essential medicinal chemistry of curcumin. J. Med. Chem. 60, 1620–1637 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. LeGrady, D. et al. Coffee consumption and mortality in the Chicago Western Electric Company Study. Am. J. Epidemiol. 126, 803–812 (1987).

    CAS  PubMed  Google Scholar 

  126. Liu, J. et al. Association of coffee consumption with all-cause and cardiovascular disease mortality. Mayo Clin. Proc. 88, 1066–1074 (2013).

    CAS  PubMed  Google Scholar 

  127. Crippa, A., Discacciati, A., Larsson, S. C., Wolk, A. & Orsini, N. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am. J. Epidemiol. 180, 763–775 (2014).

    PubMed  Google Scholar 

  128. Ding, M. et al. Association of coffee consumption with total and cause-specific mortality in 3 large prospective cohorts. Circulation 132, 2305–2315 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Loftfield, E. et al. Association of coffee consumption with overall and cause-specific mortality in a large US prospective cohort study. Am. J. Epidemiol. 182, 1010–1022 (2015).

    PubMed  PubMed Central  Google Scholar 

  130. Horrigan, L. A., Kelly, J. P. & Connor, T. J. Immunomodulatory effects of caffeine: friend or foe? Pharmacol. Ther. 111, 877–892 (2006).

    CAS  PubMed  Google Scholar 

  131. Ritter, M. et al. Caffeine inhibits cytokine expression in lymphocytes. Cytokine 30, 177–181 (2005).

    CAS  PubMed  Google Scholar 

  132. Rosenthal, L. A., Taub, D. D., Moors, M. A. & Blank, K. J. Methylxanthine-induced inhibition of the antigen- and superantigen-specific activation of T and B lymphocytes. Immunopharmacology 24, 203–217 (1992).

    CAS  PubMed  Google Scholar 

  133. Laux, D. C., Klesius, P. H. & Jeter, W. S. Suppressive effects of caffeine on the immune response of the mouse to sheep erythrocytes. Proc. Soc. Exp. Biol. Med. 144, 633–638 (1973).

    CAS  PubMed  Google Scholar 

  134. Hedström, A. K. et al. High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies. J. Neurol. Neurosurg. Psychiatry 87, 454–460 (2016).

    PubMed  PubMed Central  Google Scholar 

  135. Ng, S. C. et al. Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific. Gut 64, 1063–1071 (2015).

    PubMed  Google Scholar 

  136. Lee, Y. H., Bae, S. C. & Song, G. G. Coffee or tea consumption and the risk of rheumatoid arthritis: a meta-analysis. Clin. Rheumatol. 33, 1575–1583 (2014).

    PubMed  Google Scholar 

  137. Heliövaara, M. et al. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann. Rheum. Dis. 59, 631–635 (2000).

    PubMed  PubMed Central  Google Scholar 

  138. Mikuls, T. R. et al. Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis Rheum. 46, 83–91 (2002).

    PubMed  Google Scholar 

  139. Amaya-Amaya, J. et al. Cardiovascular disease in Latin American patients with systemic lupus erythematosus: study and a systematic review. Autoimmune Dis. 2013, 794383 (2013).

    PubMed  PubMed Central  Google Scholar 

  140. Anaya, J. M., Ramirez-Santana, C., Alzate, M. A., Molano-Gonzalez, N. & Rojas-Villarraga, A. The autoimmune ecology. Front. Immunol. http://dx.doi.org/10.3389/fimmu.2016.00139 (2016).

  141. Engler, M. B. et al. Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J. Am. Coll. Nutr. 23, 197–204 (2004).

    CAS  PubMed  Google Scholar 

  142. Fisher, N. D., Hughes, M., Gerhard-Herman, M. & Hollenberg, N. K. Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J. Hypertens. 21, 2281–2286 (2003).

    CAS  PubMed  Google Scholar 

  143. Heiss, C. et al. Vascular effects of cocoa rich in flavan-3-ols. JAMA 290, 1030–1031 (2003).

    PubMed  Google Scholar 

  144. Corti, R., Flammer, A. J., Hollenberg, N. K. & Lüscher, T. F. Cocoa and cardiovascular health. Circulation 119, 1433–1441 (2009).

    PubMed  Google Scholar 

  145. Keen, C. L., Holt, R. R., Oteiza, P. I., Fraga, C. G. & Schmitz, H. H. Cocoa antioxidants and cardiovascular health. Am. J. Clin. Nutr. 81 (Suppl. 1), 298S–303S (2005).

    CAS  PubMed  Google Scholar 

  146. Mao, T. K. et al. The effect of cocoa procyanidins on the transcription and secretion of interleukin 1β in peripheral blood mononuclear cells. Life Sci. 66, 1377–1386 (2000).

    CAS  PubMed  Google Scholar 

  147. Sanbongi, C., Suzuki, N. & Sakane, T. Polyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in vitro. Cell. Immunol. 177, 129–136 (1997).

    CAS  PubMed  Google Scholar 

  148. Mao, T. K. et al. Effect of cocoa procyanidins on the secretion of interleukin-4 in peripheral blood mononuclear cells. J. Med. Food 3, 107–114 (2000).

    CAS  Google Scholar 

  149. Ramiro, E. et al. Effect of Theobroma cacao flavonoids on immune activation of a lymphoid cell line. Br. J. Nutr. 93, 859–866 (2005).

    CAS  PubMed  Google Scholar 

  150. Ramiro-Puig, E. & Castell, M. Cocoa: antioxidant and immunomodulator. Br. J. Nutr. 101, 931–940 (2009).

    CAS  PubMed  Google Scholar 

  151. Ramos-Romero, S. et al. Effect of a cocoa flavonoid-enriched diet on experimental autoimmune arthritis. Br. J. Nutr. 107, 523–532 (2012).

    CAS  PubMed  Google Scholar 

  152. Fulgenzi, A., Bertelli, A. A., Magni, E., Ferrero, E. & Ferrero, M. E. In vivo inhibition of TNFα-induced vascular permeability by resveratrol. Transplant. Proc. 33, 2341–2343 (2001).

    CAS  PubMed  Google Scholar 

  153. Zini, R., Morin, C., Bertelli, A., Bertelli, A. A. & Tillement, J. P. Effects of resveratrol on the rat brain respiratory chain. Drugs Exp. Clin. Res. 25, 87–97 (1999).

    CAS  PubMed  Google Scholar 

  154. Bertelli, A. A. et al. Resveratrol, a natural stilbene in grapes and wine, enhances intraphagocytosis in human promonocytes: a co-factor in antiinflammatory and anticancer chemopreventive activity. Int. J. Tissue React. 21, 93–104 (1998).

    Google Scholar 

  155. Manna, S. K., Mukhopadhyay, A. & Aggarwal, B. B. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J. Immunol. 164, 6509–6519 (2000).

    CAS  PubMed  Google Scholar 

  156. Kundu, J. K., Shin, Y. K. & Surh, Y. J. Resveratrol modulates phorbol ester-induced pro-inflammatory signal transduction pathways in mouse skin in vivo: NF-κB and AP-1 as prime targets. Biochem. Pharmacol. 72, 1506–1515 (2006).

    CAS  PubMed  Google Scholar 

  157. Martinez, J. & Moreno, J. J. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem. Pharmacol. 59, 865–870 (2000).

    CAS  PubMed  Google Scholar 

  158. Bertelli, A. A. et al. Antiplatelet activity of cis-resveratrol. Drugs Exp. Clin. Res. 22, 61–63 (1996).

    CAS  PubMed  Google Scholar 

  159. Elmali, N., Baysal, O., Harma, A., Esenkaya, I. & Mizrak, B. Effects of resveratrol in inflammatory arthritis. Inflammation 30, 1–6 (2007).

    CAS  PubMed  Google Scholar 

  160. Riveiro-Naveira, R. R. et al. Resveratrol lowers synovial hyperplasia, inflammatory markers and oxidative damage in an acute antigen-induced arthritis model. Rheumatology (Oxford) 55, 1889–1900 (2016).

    CAS  Google Scholar 

  161. Coradini, K. et al. A novel approach to arthritis treatment based on resveratrol and curcumin co-encapsulated in lipid-core nanocapsules: in vivo studies. Eur. J. Pharm. Sci. 78, 163–170 (2015).

    CAS  PubMed  Google Scholar 

  162. Wang, P. et al. Effect of sodium alginate addition to resveratrol on acute gouty arthritis. Cell. Physiol. Biochem. 36, 201–207 (2015).

    PubMed  Google Scholar 

  163. Chen, H. et al. The effect of resveratrol on the recurrent attacks of gouty arthritis. Clin. Rheumatol. 35, 1189–1195 (2016).

    PubMed  Google Scholar 

  164. Qiao, Y. et al. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity. Food Funct. 5, 1241–1249 (2014).

    CAS  PubMed  Google Scholar 

  165. Shoenfeld, Y. & Caspi, D. The digital doctor. Harefuah 154, 148–149 (in Hebrew) (2015).

    CAS  PubMed  Google Scholar 

  166. Nayak, R. R. & Turnbaugh, P. J. Mirror, mirror on the wall: which microbiomes will help heal them all? BMC Med. 14, 72 (2016).

    PubMed  PubMed Central  Google Scholar 

  167. Chu, D. M. et al. The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med. 8, 77 (2016).

    PubMed  PubMed Central  Google Scholar 

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All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission. S.D. and Y. Segal share lead authorship.

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Dahan, S., Segal, Y. & Shoenfeld, Y. Dietary factors in rheumatic autoimmune diseases: a recipe for therapy?. Nat Rev Rheumatol 13, 348–358 (2017). https://doi.org/10.1038/nrrheum.2017.42

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