Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The role of diet in the aetiopathogenesis of inflammatory bowel disease

Nature Reviews Gastroenterology & Hepatology volume 15, pages 525–535 (2018)Cite this article

Subjects

Abstract

Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene–environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions.

Key points

  • Epidemiological studies have identified a number of potential dietary risk factors for Crohn’s disease and ulcerative colitis.

  • Early results from dietary intervention studies in Crohn’s disease and ulcerative colitis have been promising, particularly in paediatric patients, but high-quality randomized trials are needed to assess efficacy.

  • Preliminary gene–environment and microbiome studies have demonstrated an interaction between diet, host genetics and the gut microbiota in the aetiopathogenesis of Crohn’s disease and ulcerative colitis.

  • Large-scale studies are needed to prospectively examine the role of diet in the aetiopathogenesis of Crohn’s disease and ulcerative colitis in the context of host genetics and the gut microbiota.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The pathophysiology of IBD.
Fig. 2: Potential mechanisms underpinning the relationship between diet and IBD.
Fig. 3: The complex causal relationship between diet and IBD.

Similar content being viewed by others

References

  1. Molodecky, N. A. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142, 46–54.e2 (2012).

    Article  PubMed  Google Scholar 

  2. Burisch, J., Jess, T., Martinato, M., Lakatos, P. L. & EpiCom, E. The burden of inflammatory bowel disease in Europe. J. Crohns Colitis 7, 322–337 (2013).

    Article  PubMed  Google Scholar 

  3. Kappelman, M. D. et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin. Gastroenterol. Hepatol. 5, 1424–1429 (2007).

    Article  PubMed  Google Scholar 

  4. Ferguson, A., Sedgwick, D. M. & Drummond, J. Morbidity of juvenile onset inflammatory bowel disease: effects on education and employment in early adult life. Gut 35, 665–668 (1994).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Kappelman, M. D. et al. Direct health care costs of Crohn’s disease and ulcerative colitis in US children and adults. Gastroenterology 135, 1907–1913 (2008).

    Article  PubMed  Google Scholar 

  6. Longobardi, T., Jacobs, P. & Bernstein, C. N. Work losses related to inflammatory bowel disease in the United States: results from the National Health Interview Survey. Am. J. Gastroenterol. 98, 1064–1072 (2003).

    PubMed  Google Scholar 

  7. Franke, A. et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat. Genet. 42, 1118–1125 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Kenny, E. E. et al. A genome-wide scan of Ashkenazi Jewish Crohn’s disease suggests novel susceptibility loci. PLoS Genet. 8, e1002559 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Kugathasan, S. & Amre, D. Inflammatory bowel disease — environmental modification and genetic determinants. Pediatr. Clin. North Amer. 53, 727–749 (2006).

    Article  Google Scholar 

  10. Tysk, C., Lindberg, E., Jarnerot, G. & Floderus-Myrhed, B. Ulcerative colitis and Crohn’s disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut 29, 990–996 (1988).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Ng, S. C. et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390, 2769–2778 (2018).

    Article  Google Scholar 

  12. Williams, C. N. Does the incidence of IBD increase when persons move from a low- to a high-risk area? Inflamm. Bowel Dis. 14 (Suppl. 2), S41–S42 (2008).

    Article  PubMed  Google Scholar 

  13. Probert, C. S., Jayanthi, V., Pinder, D., Wicks, A. C. & Mayberry, J. F. Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire. Gut 33, 687–693 (1992).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Benchimol, E. I. et al. Inflammatory bowel disease in immigrants to Canada and their children: a population-based cohort study. Am. J. Gastroenterol. 110, 553–563 (2015).

    Article  PubMed  Google Scholar 

  15. Li, X., Sundquist, J., Hemminki, K. & Sundquist, K. Risk of inflammatory bowel disease in first- and second-generation immigrants in Sweden: a nationwide follow-up study. Inflamm. Bowel Dis. 17, 1784–1791 (2011).

    Article  PubMed  Google Scholar 

  16. Albenberg, L. G. & Wu, G. D. Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 146, 1564–1572 (2014).

    Article  PubMed  CAS  Google Scholar 

  17. Poullis, A., Foster, R., Shetty, A., Fagerhol, M. K. & Mendall, M. A. Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiol. Biomarkers Prev. 13, 279–284 (2004).

    Article  PubMed  CAS  Google Scholar 

  18. Martinez-Medina, M. et al. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut 63, 116–124 (2014).

    Article  PubMed  CAS  Google Scholar 

  19. Stenman, L. K., Holma, R., Eggert, A. & Korpela, R. A novel mechanism for gut barrier dysfunction by dietary fat: epithelial disruption by hydrophobic bile acids. Am. J. Physiol. Gastrointest. Liver Physiol. 304, G227–234 (2013).

    Article  PubMed  CAS  Google Scholar 

  20. Halmos, E. P. & Gibson, P. R. Dietary management of IBD — insights and advice. Nat. Rev. Gastroenterol. Hepatol. 12, 133–146 (2015).

    Article  PubMed  CAS  Google Scholar 

  21. Borrelli, O. et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn’s disease: a randomized controlled open-label trial. Clin. Gastroenterol. Hepatol. 4, 744–753 (2006).

    Article  PubMed  Google Scholar 

  22. Zachos, M., Tondeur, M. & Griffiths, A. M. Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst. Rev. 1, CD000542 (2007).

    Google Scholar 

  23. Charlebois, A., Rosenfeld, G. & Bressler, B. The impact of dietary interventions on the symptoms of inflammatory bowel disease: a systematic review. Crit. Rev. Food Sci. Nutr. 56, 1370–1378 (2016).

    Article  PubMed  CAS  Google Scholar 

  24. Persson, P. G., Ahlbom, A. & Hellers, G. Diet and inflammatory bowel disease: a case-control study. Epidemiology 3, 47–52 (1992).

    Article  PubMed  CAS  Google Scholar 

  25. Chapman-Kiddell, C. A., Davies, P. S., Gillen, L. & Radford-Smith, G. L. Role of diet in the development of inflammatory bowel disease. Inflamm. Bowel Dis. 16, 137–151 (2010).

    Article  PubMed  Google Scholar 

  26. Tragnone, A. et al. Dietary habits as risk factors for inflammatory bowel disease. Eur. J. Gastroenterol. Hepatol. 7, 47–51 (1995).

    PubMed  CAS  Google Scholar 

  27. Willett, W. C., Reynolds, R. D., Cottrell-Hoehner, S., Sampson, L. & Browne, M. L. Validation of a semi-quantitative food frequency questionnaire: comparison with a 1-year diet record. J. Am. Diet Assoc. 87, 43–47 (1987).

    PubMed  CAS  Google Scholar 

  28. Colditz, G. A., Manson, J. E. & Hankinson, S. E. The Nurses’ Health Study: 20-year contribution to the understanding of health among women. J. Womens Health 6, 49–62 (1997).

    Article  PubMed  CAS  Google Scholar 

  29. Ananthakrishnan, A. N. et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology 145, 970–977 (2013).

    Article  PubMed  CAS  Google Scholar 

  30. Ananthakrishnan, A. N. et al. Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease. Gut 63, 776–784 (2014).

    Article  PubMed  CAS  Google Scholar 

  31. Khalili, H. et al. Dietary iron and heme iron consumption, genetic susceptibility, and risk of crohn’s disease and ulcerative colitis. Inflamm. Bowel Dis. 23, 1088–1095 (2017).

    Article  PubMed  Google Scholar 

  32. Bettelli, E. et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235–238 (2006).

    Article  PubMed  CAS  Google Scholar 

  33. Eil, R. et al. Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature 537, 539–543 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Yosef, N. et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature 496, 461–468 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Bao, S. et al. Zinc modulates the innate immune response in vivo to polymicrobial sepsis through regulation of NF-kappaB. Am. J. Physiol. Lung Cell. Mol. Physiol. 298, L744–L754 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Finamore, A., Massimi, M., Conti Devirgiliis, L. & Mengheri, E. Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 cells. J. Nutr. 138, 1664–1670 (2008).

    Article  PubMed  CAS  Google Scholar 

  39. Prasad, A. S. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr. Opin. Clin. Nutr. Metab. Care 12, 646–652 (2009).

    Article  PubMed  CAS  Google Scholar 

  40. Khalili, H. et al. Identification and characterization of a novel association between dietary potassium and risk of crohn’s disease and ulcerative colitis. Front. Immunol. 7, 554 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ananthakrishnan, A. N. et al. Zinc intake and risk of Crohn’s disease and ulcerative colitis: a prospective cohort study. Int. J. Epidemiol. 44, 1995–2005 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Riboli, E. et al. European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Publ. Health Nutr. 5, 1113–1124 (2002).

    Article  CAS  Google Scholar 

  43. Ferrari, P. et al. Within- and between-cohort variation in measured macronutrient intakes, taking account of measurement errors, in the European Prospective Investigation into Cancer and Nutrition study. Am. J. Epidemiol. 160, 814–822 (2004).

    Article  PubMed  Google Scholar 

  44. Hart, A. R. et al. Diet in the aetiology of ulcerative colitis: a European prospective cohort study. Digestion 77, 57–64 (2008).

    Article  PubMed  Google Scholar 

  45. IBD in EPIC Study Investigators et al. Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study. Gut 58, 1606–1611 (2009).

    Article  CAS  Google Scholar 

  46. Calder, P. C. Fatty acids and inflammation: the cutting edge between food and pharma. Eur. J. Pharmacol. 668 (Suppl. 1), S50–S58 (2011).

    Article  PubMed  CAS  Google Scholar 

  47. Simopoulos, A. P. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed. Pharmacother. 60, 502–507 (2006).

    Article  PubMed  CAS  Google Scholar 

  48. Chan, S. S. et al. Association between high dietary intake of the n-3 polyunsaturated fatty acid docosahexaenoic acid and reduced risk of Crohn’s disease. Aliment. Pharmacol. Ther. 39, 834–842 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Chan, S. S. et al. Carbohydrate intake in the etiology of Crohn’s disease and ulcerative colitis. Inflamm. Bowel Dis. 20, 2013–2021 (2014).

    Article  PubMed  Google Scholar 

  50. Racine, A. et al. Dietary patterns and risk of inflammatory bowel disease in Europe: results from the EPIC study. Inflamm. Bowel Dis. 22, 345–354 (2016).

    Article  PubMed  Google Scholar 

  51. Opstelten, J. L. et al. Dairy products, dietary calcium, and risk of inflammatory bowel disease: results from a European prospective cohort investigation. Inflamm. Bowel Dis. 22, 1403–1411 (2016).

    Article  PubMed  Google Scholar 

  52. Bergmann, M. M. et al. No association of alcohol use and the risk of ulcerative colitis or Crohn’s disease: data from a European Prospective cohort study (EPIC). Eur. J. Clin. Nutr. 71, 512–518 (2017).

    Article  PubMed  CAS  Google Scholar 

  53. Gavaler, J. S., Rosenblum, E. R., Deal, S. R. & Bowie, B. T. The phytoestrogen congeners of alcoholic beverages: current status. Proc. Soc. Exp. Biol. Med. 208, 98–102 (1995).

    Article  PubMed  CAS  Google Scholar 

  54. Seifried, H. E., Anderson, D. E., Fisher, E. I. & Milner, J. A. A review of the interaction among dietary antioxidants and reactive oxygen species. J. Nutr. Biochem. 18, 567–579 (2007).

    Article  PubMed  CAS  Google Scholar 

  55. Yamamoto, T., Nakahigashi, M. & Saniabadi, A. R. Review article: diet and inflammatory bowel disease — epidemiology and treatment. Aliment. Pharmacol. Ther. 30, 99–112 (2009).

    Article  PubMed  CAS  Google Scholar 

  56. Barton, L. L., Ritz, N. L., Fauque, G. D. & Lin, H. C. Sulfur cycling and the intestinal microbiome. Dig. Dis. Sci. 62, 2241–2257 (2017).

    Article  PubMed  CAS  Google Scholar 

  57. Kim, I. W. et al. Western-style diets induce macrophage infiltration and contribute to colitis-associated carcinogenesis. J. Gastroenterol. Hepatol. 25, 1785–1794 (2010).

    Article  PubMed  CAS  Google Scholar 

  58. Breton, J. et al. Intrinsic immunomodulatory effects of low-digestible carbohydrates selectively extend their anti-inflammatory prebiotic potentials. Biomed. Res. Int. 2015, 162398 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Le Leu, R. K., Young, G. P., Hu, Y., Winter, J. & Conlon, M. A. Dietary red meat aggravates dextran sulfate sodium-induced colitis in mice whereas resistant starch attenuates inflammation. Dig. Dis. Sci. 58, 3475–3482 (2013).

    Article  PubMed  CAS  Google Scholar 

  60. Degagne, E. et al. Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs. J. Clin. Invest. 124, 5368–5384 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Jantchou, P., Morois, S., Clavel-Chapelon, F., Boutron-Ruault, M. C. & Carbonnel, F. Animal protein intake and risk of inflammatory bowel disease: the E3N prospective study. Am. J. Gastroenterol. 105, 2195–2201 (2010).

    Article  PubMed  CAS  Google Scholar 

  62. Liang, J. et al. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 23, 107–120 (2013).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  64. Zhang, W. C. et al. High salt primes a specific activation state of macrophages, M(Na). Cell Res. 25, 893–910 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Hunter, D. J. Gene-environment interactions in human diseases. Nat. Rev. Genet. 6, 287–298 (2005).

    Article  PubMed  CAS  Google Scholar 

  66. Khor, B., Gardet, A. & Xavier, R. J. Genetics and pathogenesis of inflammatory bowel disease. Nature 474, 307–317 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Leone, V. A., Cham, C. M. & Chang, E. B. Diet, gut microbes, and genetics in immune function: can we leverage our current knowledge to achieve better outcomes in inflammatory bowel diseases? Curr. Opin. Immunol. 31, 16–23 (2014).

    Article  PubMed  CAS  Google Scholar 

  68. Van Der Sloot, K. W. et al. Visceral adiposity, genetic susceptibility, and risk of complications among individuals with Crohn’s disease. Inflamm. Bowel Dis. 23, 82–88 (2017).

    Article  Google Scholar 

  69. Ananthakrishnan, A. N. et al. Genetic polymorphisms in fatty acid metabolism modify the association between dietary n3: n6 intake and risk of ulcerative colitis: a prospective cohort study. Inflamm. Bowel Dis. 23, 1898–1904 (2017).

    Article  PubMed  Google Scholar 

  70. Costea, I. et al. Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn’s disease. Gastroenterology 146, 929–931 (2014).

    Article  PubMed  CAS  Google Scholar 

  71. Hargreaves, C. E. et al. Fcgamma receptors: genetic variation, function, and disease. Immunol. Rev. 268, 6–24 (2015).

    Article  PubMed  CAS  Google Scholar 

  72. Stein, M. P. et al. C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific. J. Clin. Invest. 105, 369–376 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Stein, M. P., Mold, C. & Du Clos, T. W. C-reactive protein binding to murine leukocytes requires Fc gamma receptors. J. Immunol. 164, 1514–1520 (2000).

    Article  PubMed  CAS  Google Scholar 

  74. Bharadwaj, D. et al. The major receptor for C-reactive protein on leukocytes is Fcγ receptor II. J. Exp. Med. 190, 585–590 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Zhou, L. et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8, 967–974 (2007).

    Article  PubMed  CAS  Google Scholar 

  76. Fantini, M. C. et al. IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells. Eur. J. Immunol. 37, 3155–3163 (2007).

    Article  PubMed  CAS  Google Scholar 

  77. Caspi, A. et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386–389 (2003).

    Article  PubMed  CAS  Google Scholar 

  78. Risch, N. et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301, 2462–2471 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L. & Gordon, J. I. Human nutrition, the gut microbiome and the immune system. Nature 474, 327–336 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Brown, K., DeCoffe, D., Molcan, E. & Gibson, D. L. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients 4, 1095–1119 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. D’Haens, G. R. et al. Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 114, 262–267 (1998).

    Article  PubMed  Google Scholar 

  82. Sellon, R. K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224–5231 (1998).

    PubMed  PubMed Central  CAS  Google Scholar 

  83. Hudcovic, T., Stepankova, R., Cebra, J. & Tlaskalova-Hogenova, H. The role of microflora in the development of intestinal inflammation: acute and chronic colitis induced by dextran sulfate in germ-free and conventionally reared immunocompetent and immunodeficient mice. Folia Microbiol. 46, 565–572 (2001).

    Article  CAS  Google Scholar 

  84. Morgan, X. C. et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 13, R79 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Nagalingam, N. A. & Lynch, S. V. Role of the microbiota in inflammatory bowel diseases. Inflamm. Bowel Dis. 18, 968–984 (2012).

    Article  PubMed  Google Scholar 

  86. Spor, A., Koren, O. & Ley, R. Unravelling the effects of the environment and host genotype on the gut microbiome. Nat. Rev. Microbiol. 9, 279–290 (2011).

    Article  PubMed  CAS  Google Scholar 

  87. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Ijssennagger, N. et al. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon. Proc. Natl Acad. Sci. USA 112, 10038–10043 (2015).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  90. Ijssennagger, N., de Wit, N., Muller, M. & van der Meer, R. Dietary heme-mediated PPARalpha activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon. PLoS ONE 7, e43260 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. N., I. J. et al. Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk. PLoS ONE 7, e49868 (2012).

    Article  CAS  Google Scholar 

  92. Seregin, S. S. et al. NLRP6 protects Il10(−/−) mice from colitis by limiting colonization of Akkermansia muciniphila. Cell Rep. 19, 733–745 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Werner, T. et al. Depletion of luminal iron alters the gut microbiota and prevents Crohn’s disease-like ileitis. Gut 60, 325–333 (2011).

    Article  PubMed  CAS  Google Scholar 

  94. Turnbaugh, P. J., Backhed, F., Fulton, L. & Gordon, J. I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213–223 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  96. Devkota, S. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487, 104–108 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Kevans, D. et al. IBD genetic risk profile in healthy first-degree relatives of crohn’s disease patients. J. Crohns Colitis 10, 209–215 (2016).

    Article  PubMed  Google Scholar 

  98. Kevans, D. et al. Determinants of intestinal permeability in healthy first-degree relatives of individuals with Crohn’s disease. Inflamm. Bowel Dis. 21, 879–887 (2015).

    Article  PubMed  Google Scholar 

  99. Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565–569 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  101. Imhann, F. et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut https://doi.org/10.1136/gutjnl-2016-312135 (2016).

  102. Knights, D. et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med. 6, 107 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Turpin, W. et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat. Genet. 48, 1413–1417 (2016).

    Article  PubMed  CAS  Google Scholar 

  104. Bonder, M. J. et al. The effect of host genetics on the gut microbiome. Nat. Genet. 48, 1407–1412 (2016).

    Article  PubMed  CAS  Google Scholar 

  105. Feskanich, D. et al. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J. Am. Diet Assoc. 93, 790–796 (1993).

    Article  PubMed  CAS  Google Scholar 

  106. Rimm, E. et al. Reproducibility and validity of an expanded self-administered semiquantitative food questionnaire among health professionals. Am. J. Epidemiol. 135, 1114–1126 (1992).

    Article  PubMed  CAS  Google Scholar 

  107. Rockett, H. R. et al. Validation of a youth/adolescent food frequency questionnaire. Prev. Med. 26, 808–816 (1997).

    Article  PubMed  CAS  Google Scholar 

  108. Rockett, H. R., Wolf, A. M. & Colditz, G. A. Development and reproducibility of a food frequency questionnaire to assess diets of older children and adolescents. J. Am. Diet Assoc. 95, 336–340 (1995).

    Article  PubMed  CAS  Google Scholar 

  109. Ascherio, A. et al. Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women. J. Nutr. 122, 1792–1801 (1992).

    Article  PubMed  CAS  Google Scholar 

  110. Romieu, I. et al. Food predictors of plasma beta-carotene and alpha-tocopherol: validation of a food frequency questionnaire. Am. J. Epidemiol. 131, 864–876 (1990).

    Article  PubMed  CAS  Google Scholar 

  111. Willett, W. C. et al. Validation of dietary questionnaire with plasma carotenoid and alpha-tocopherol level. Am. J. Clin. Nutr. 38, 631–639 (1983).

    Article  PubMed  CAS  Google Scholar 

  112. Giovannucci, E. et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J. Natl Cancer Inst. 85, 875–884 (1993).

    Article  PubMed  CAS  Google Scholar 

  113. Hunter, D. J. et al. Comparison of measures of fatty acid intake by subcutaneous fat aspirate, food frequency questionnaire, and diet records in a free-living population of US men. Am. J. Epidemiol. 135, 418–427 (1992).

    Article  PubMed  CAS  Google Scholar 

  114. London, S. J. et al. Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women. Am. J. Clin. Nutr. 54, 340–345 (1991).

    Article  PubMed  CAS  Google Scholar 

  115. Yuan, C. et al. Validity of a dietary questionnaire assessed by comparison with multiple weighed dietary records or 24-hour recalls. Am. J. Epidemiol. 185, 570–584 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Ordás, I., Eckmann, L., Talamini, M., Baumgart, D. C. & Sandborn, W. J. Ulcerative colitis. Lancet 380, 1606–1619 (2012).

    Article  PubMed  Google Scholar 

  117. Ananthakrishnan, A. N. et al. High school diet and risk of Crohn’s disease and ulcerative colitis. Inflamm. Bowel Dis. 21, 2311–2319 (2015).

    Article  PubMed  Google Scholar 

  118. Bergmann, M. M. et al. No association of alcohol use and the risk of ulcerative colitis or Crohn’s disease: data from a European Prospective cohort study (EPIC). Eur. J. Clin. Nutr. 71, 566 (2017).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

H.K. is funded by the US National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681 and R03). A.T.C. is funded by the US National Institutes of Health (NIH) grant K24 DK098311, a Stuart and Suzanne Steele Massachusetts General Hospital (MGH) Research Scholar Award and a Senior Investigator Award from the Crohn’s and Colitis Foundation.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Hamed Khalili, Paul Lochhead, Ashwin N. Ananthakrishnan & Andrew T. Chan

  2. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Hamed Khalili, Ashwin N. Ananthakrishnan & Andrew T. Chan

  3. Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, UK

    Simon S. M. Chan & Andrew R. Hart

  4. Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich, UK

    Simon S. M. Chan & Andrew R. Hart

  5. Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA

    Andrew T. Chan

  6. Broad Institute, Cambridge, MA, USA

    Andrew T. Chan

Authors
  1. Hamed Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon S. M. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Lochhead
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ashwin N. Ananthakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew R. Hart
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew T. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.K., S.S.M.C. and A.N.A. made substantial contributions to discussion of the content. H.K., P.L. and A.R.H. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Andrew T. Chan.

Ethics declarations

Competing interests

H.K. has received consulting fees from AbbVie and Samsung Bioepis. H.K. also receives funding from Takeda. S.S.M.C. has received consulting fees from AbbVie and Ferring Pharmaceuticals. P.L. is supported by a career development grant by the Crohn’s and Colitis Foundation (CCF). A.N.A. is a member of the scientific advisory board for Exact Sciences, AbbVie and Cubist Pharmaceuticals. A.T.C. has served as a consultant for Bayer Healthcare, Pfizer and Takeda. A.R.H. declares no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khalili, H., Chan, S.S.M., Lochhead, P. et al. The role of diet in the aetiopathogenesis of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 15, 525–535 (2018). https://doi.org/10.1038/s41575-018-0022-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-018-0022-9

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing