The urban diet and Crohn's disease: is there a relationship? : European Journal of Gastroenterology & Hepatology

Secondary Logo

Journal Logo

Leading Articles

The urban diet and Crohn's disease: is there a relationship?

Mahmud, Nasir; Weir, Donald G.

Author Information
European Journal of Gastroenterology & Hepatology: February 2001 - Volume 13 - Issue 2 - p 93-95
  • Free


Although the aetiology and pathogenesis of Crohn's disease remain to be elucidated, recent advances are beginning to suggest where the answers may lie. While there can be no doubt that genetic influences causing immune dysfunction play a role, as can be demonstrated in twin and family studies as well as genetic linkage analyses [1–4], the relationship is complex [5]. For instance, it is suggested that immune mediated cytokine gene activation may be important [6,7], causing stimulation of mononuclear cells derived from both the circulation and the intestinal mucosa of Crohn's disease patients to produce cytokines and to express their receptors [8]. This suggests that cytokine genes are important candidate genes in inflammatory bowel disease (IBD). However, allelic association studies have failed to demonstrate that the relevant genes encoding these cytokines are important determinants of disease susceptibility [9]. Given the ability of specific antigen(s) to penetrate the mucosal defence barrier and mediate an immunological response, the evidence that this reaction is in some way specific for IBD patients remains inconclusive.

The answer may lie in the control of the gut luminal environment and the ability of certain antigens to penetrate the mucosa. In addition, various specific and non-specific environmental factors are considered to be associated with the induction and/or exacerbation of IBD [10,11]. The incidence of Crohn's disease is higher in urban areas than in the surrounding rural environment [10,11]. Furthermore, the prevalence of the disease has increased over the last decade in built-up urban districts during a period when genetic factors, potentially predisposing to the disease, would have remained stable [10,11]. All of this suggests that dietary factors may be important.

Patients with Crohn's disease have been shown to have a higher dietary intake of sucrose and refined carbohydrates and a reduced fruit and vegetables intake when compared with controls [12,13]. Such studies are bedevilled by the problem of whether such differences are post hoc or propter hoc the onset of the disease. Reif and co-workers [14] have endeavoured to assess pre-illness dietary factors and have suggested that the onset of IBD was positively associated with a high sucrose intake and negatively with fructose, magnesium and ascorbic acid, which are present in fruit. King and colleagues [15] have shown intolerance to chocolate in some patients and an aversion in most to dairy products such as cow's milk and yeast. Others have shown a positive association with cola drinks, chewing gum and chocolate, all of which have a high sugar content, and a negative association with citrus fruit consumption [16].

It is also suggested that a high intake of dietary fat (ω-6 fatty acids) is positively associated with Crohn's disease [17]; fish oil (ω-3 fatty acids) was associated with a lower relapse rate [18], which is possibly related to their immunomodulatory and anti-inflammatory properties [19]. It is well appreciated that smoking is positively associated with Crohn's disease [20] and negatively with ulcerative colitis [21].

Since the pioneering work of O'Morain and colleagues (1984), it has been known that the use of an elemental diet is as effective as corticosteroids in inducing a remission in acute Crohn's disease over the short term [22]. It was soon realized that patients relapsed on returning to a normal diet. If, however, they remained on an exclusion diet the remission was maintained [23]. This was subsequently confirmed in a multi-centre trial of an exclusion diet versus corticosteroids, following elemental diet induced remission [24]. This suggested that there was something in an ordinary diet which was not present in the exclusion diet, and which on penetrating the mucosal defence mechanism of the terminal ileum set up a pathogenic immune process. Since most nutrients are absorbed in the upper intestine, the putative dietary factor present in the normal diet had to be a poorly absorbed non-nutrient.

Recently, Powell and colleagues [25] have suggested that inert, inorganic, non-nutrient microparticles, such as natural contaminants (soil and dust), food additives and anti-caking agents may combine with intestinal luminal components, such as bacterial cell wall lipopolysaccharides, which are present in abundance in the gut, to form antigenic particles which, when taken up by the mucosa, can mediate immune responses in mononuclear cells present both locally in the mucosa and in the systemic circulation. These microparticles, especially titanium dioxide and aluminosilicates, have been identified in the phagocytes of intestinal lymphoid aggregates, present predominantly in the distal small intestine, the commonest site affected by Crohn's disease [26]. Data from the Ministry of Agriculture, Fisheries and Food (1993) suggest that the normal western diet contains significant quantities of such microparticles [27].

In this issue of the journal, the same group has published a preliminary double blind study of the efficacy of a low microparticle diet, as compared with a normal diet, in the management of active corticosteroid treated ileal or ileo-colonic Crohn's disease over a 4-month period [28]. The study demonstrates that the patients allocated to the low microparticle diet had a significant reduction in their disease activity and the need for corticosteroids when compared with the control group on a normal diet. As pointed out by the authors ‘elemental diets are free of titanium dioxide and probably also of other inorganic particulate additives', which they suggest could explain their therapeutic efficacy. The main value of the microparticle free diet when compared with the elemental diet is its enhanced tolerance by the patient and its relatively low cost. This suggests that such diets might be applicable for use on a long term basis. The results of the authors’ ongoing follow-up multi-centre trial will be eagerly awaited.

The reason why patients who develop Crohn's disease are at risk from such dietary microparticles presumably relates to various additional factors which affect their permeability, such as enteric infections, toxins or genetic properties [29] or the possible deficiency or malfunction of intestinal trefoil factors. A recent study by Mashimo and colleagues has demonstrated that intestinal trefoil factor, a protein secreted throughout the bowel, plays an important role in maintaining the integrity of epithelial cells and mucosal healing [30]. Such a mechanism has been implicated in the generation of persistent immunological responses to luminal antigen(s), which may lead to chronic intestinal inflammation [31].

The microparticle hypothesis will still have to be confirmed elsewhere before it can be accepted as a part of the pathogenesis of Crohn's disease. Nevertheless, if as suggested, the urban diet turns out to have significantly higher quantities of microparticles in the form of food additives than its rural counterpart, it could answer many questions, not least of which is an explanation for the rising incidence of the disease in urban society today.


1. Tysk C, Lindberg C, Jarnerot G, Floderus-Myrhed B. Ulcerative colitis and Crohn's disease in an un-selected population of monozygotic and dizygotic twins. : A study of heritability and the influence of smoking. Gut 1988; 29: 990 –996.
2. Monsen U, Brostrom O, Nordenvall B, Sorstad J, Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis. Scand J Gastroenterol 1987; 22: 214 –218.
3. Mayberry JF, Rhodes J, Newcombe RG. Familial prevalence of inflammatory bowel disease in relatives with Crohn's disease. BMJ 1980; 1: 84. 84.
4. Nakajima A, Matisuhashi N, Kodama T, Nazaki Y, Takazoe M, Kimura A. HLA linked susceptibility and resistance gene in Crohn's disease. Gastroenterology 1995; 109: 1462 –1467.
5. Satsangi J, Welsh KI, Bunce M, Julier C, Farrant JM, Bell JI. et al. Contribution of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet 1996; 347: 1212 –1217.
6. Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W. Antibody to IL-2 abrogates established experimental colitis in mice. J Exp Med 1995; 182: 1281 –1290.
7. Stuber E, Strober W, Neurath MF. Blocking the CD40L–CD40 interaction in vivo specifically prevents the priming of TH1-T cells through the inhibition of IL-12 secretion. J Exp Med 1996; 183: 183 –189.
8. Matsuura T, West GA, Youngman KR, Klein JS, Fiocchi C. Immune activation genes in inflammatory bowel disease. Gastroenterology 1993; 104: 448 –458.
9. Satsangi J, Parkes M, Jewell DP, Bell JI. Genetics of inflammatory bowel disease. Clin Sci (Colch) 1998; 94: 473 –478.
10. Gilat T, Langman MJS, Rozen P. Environmental factors in inflammatory bowel disease. Front Gastrointest Res 1986; 11: 158 –176.
11. Gilat T, Hacohen D, Lilos P, Langman MJS. Childhood factors in ulcerative colitis and Crohn's disease: an international cooperative study. Scand J Gastroenterol 1987; 22: 385 –389.
12. Mayberry JF, Rhodes J, Newcombe RG. Increased sugar consumption in Crohn's disease. Digestion 1980; 20: 323 –326.
13. Mayberry JF, Rhodes J, Allan R, Newcombe RG, Regan GM, Chamberlain LM, Wragg KG. Diet in Crohn's disease. Dig Dis Sci 1981; 26: 444 –448.
14. Reif S, Klein I, Lubin F, Farbstein M, Hallak A, Gilat T. Pre-illness dietary factors in inflammatory bowel disease. Gut 1997; 40: 754 –760.
15. King TS, Woolner JT, Hunter JO. The dietary management of Crohn's disease. Aliment Pharmacol Ther 1997; 11: 17 –31.
16. Martini GA, Brandes JW. Increased consumption of refined sugar in patients with Crohn's disease. Klin Wochenschr 1976; 54: 367 –371.
17. Shoda R, Matsueda K, Shigwa Y, Umeda N. Epidemiological analysis of Crohn's disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relate to the increased incidence of Crohn's disease in Japan. Am J Clin Nutr 1996; 63: 741 –745.
18. Belluzzi A, Brignola C, Camperi M, Pera A, Boschi S, Miglioli M. Effect of an enteric coated fish oil preparation on relapses in Crohn's disease. N Engl J Med 1996; 334: 1557 –1560.
19. Calder PC. Immunomodulatory and antiinflammatory effects of n-3 polysaturated fatty acid. Proc Nutr Soc 1996; 55: 737 –774.
20. Forbes A. Smoking and inflammatory bowel disease. Eur J Gastroenterol Hepatol 1996; 8: 761 –763.
21. Silverstein MD, Lashner BA, Hanauer SB. Cigarette smoking and ulcerative colitis: a case–control study. Mayo Clin Proc 1994; 69: 425 –429.
22. O'Morain C, Segal AW, Levi AJ. Elemental diet as primary treatment of acute Crohn's disease. Br Med J 1984; 288: 1859 –1862.
23. Alun Jones V, Dickinson RJ, Workman E, Wilson AJ, Freeman AH, Hunter JO. Crohn's disease: maintenance of remission by diet. Lancet 1985; ii: 177 –180.
24. Riordan AM, Hunter JO, Cowen RE, Crampton JR, Davidson AR, Dickinson RJ. et al. Treatment of active Crohn's disease by exclusion diet: East Anglian Multicentre Controlled Trial. Lancet 1993; 342: 1131 –1134.
25. Powell JJ, Harvey RS, Ashwood P, Wolstencroft R, Gershwin ME, Thompson RP. Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease. J Autoimmun 2000; 14: 99 –105.
26. Powell JJ, Ainley CC, Harvey RSJ, Mason IM, Kendall MD, Sankley EA. et al. Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue. Gut 1996; 38: 390 –395.
27. Ministry of Agriculture, Fisheries and Food. Dietary Intake of Food Additives in UK. Initial Surveillance. Food Surveillance Paper No. 32. London: HMSO; 1993.
28. Lomer MCE, Harvey RSJ, Evans SM, Thompson RPH, Powell JJ. Efficacy and tolerability of a low microparticle diet in a double blind randomised pilot study in Crohn's disease. Eur J Gastroenterol Hepatol 2000; 13: 101 –106.
29. Hollander D, Vadheim CM, Brettholz E, Peterson GM, Delahunty T, Rotter JI. Increased intestinal permeability in patients with Crohn's disease and their relatives: a possible aetiological factor. Ann Intern Med 1986; 105: 883 –885.
30. Mashimo H, Wu DC, Podolsky DK, Fishman MC. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science 1996; 274: 262 –265.
31. Sator RB. Pathogenesis and immune mechanisms of chronic inflammatory bowel disease. Am J Gastroenterol 1997; 92 (suppl) : 5S –11S.

Crohn's disease; inflammatory bowel disease; microparticle diet; dietary management of Crohn's disease

© 2001 Lippincott Williams & Wilkins, Inc.