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

Mahmud, Nasir; Weir, Donald G.

European Journal of Gastroenterology & Hepatology: February 2001 - Volume 13 - Issue 2 - p 93-95
Leading Articles
  •  Various specific and non-specific environmental factors are considered to be associated with the induction and/or exacerbation of IBD.
  •  Patients with CD have a higher dietary intake of sucrose, refined carbohydrates and ω-6 fatty acids, and reduced fruit and vegetables.
  •  The incidence of CD is higher in urban areas. Urban diets contain high levels of inert non-nutrient microparticles (natural contaminants such as soil and dust, food additives and anti-caking agents). When taken up by the mucosal mononuclear cells these may mediate a pathogenic immune response.
  •  Elemental and exclusion diets (low in microparticles) have been shown to be effective in CD.
  •  A preliminary trial reported in this issue demonstrates that a microparticle free diet significantly reduced the disease activity and need for corticosteroids in CD patients, compared to those on a normal diet. The results of an on-going multi-centre trial are awaited.
  •  The main value of a microparticle free diet, when compared with elemental and exclusion diets, is its enhanced tolerance by the patients and its relatively low cost.

• Various specific and non-specific environmental factors are considered to be associated with the induction and/or exacerbation of IBD.• Patients with CD have a higher dietary intake of sucrose, refined carbohydrates and ω-6 fatty acids, and reduced fruit and vegetables.• The incidence of CD is higher in urban areas. Urban diets contain high levels of inert non-nutrient microparticles (natural contaminants such as soil and dust, food additives and anti-caking agents). When taken up by the mucosal mononuclear cells these may mediate a pathogenic immune response.• Elemental and exclusion diets (low in microparticles) have been shown to be effective in CD.• A preliminary trial reported in this issue demonstrates that a microparticle free diet significantly reduced the disease activity and need for corticosteroids in CD patients, compared to those on a normal diet. The results of an on-going multi-centre trial are awaited.• The main value of a microparticle free diet, when compared with elemental and exclusion diets, is its enhanced tolerance by the patients and its relatively low cost. The aetiology and pathogenesis of Crohn's disease (CD) remain to be elucidated. In addition to genetic influences and immune mediated cytokine gene activation, various specific and non-specific environmental factors are considered to be associated with the induction and/or exacerbation of inflammatory bowel disease (IBD). The incidence of CD is higher in urban areas than in the rural environment. Patients with CD have a higher dietary intake of sucrose, refined carbohydrates and ω-6 fatty acids, and reduced intake of fruit and vegetables. Elemental and exclusion diets are known to be effective in CD. However, patients relapse on returning to a normal diet, which suggests that there is something in an ordinary diet which, on penetrating the mucosal defence mechanism of the terminal ileum, generates a pathogenic immune process. It has been suggested that the urban diet contains large quantities of inert inorganic non-nutrient microparticles, such as natural contaminants (soil and dust), food additives and anti-caking agents which may combine with intestinal luminal components such as bacterial cell wall lipopolysaccharides, to form antigenic particles. When these are taken up by mucosal mononuclear cells they can mediate immune reactions both locally in the mucosa and in the systemic circulation. In a study published in this issue of the journal, CD patients allocated to a low microparticle diet experienced a significant reduction in CD activity and the requirement for corticosteroids, when compared with the control group on a normal diet. The main advantage of the microparticle free diet, when compared with elemental and exclusion diets, is its enhanced tolerance by the patients and its relatively low cost. The preliminary results may give an explanation for the rising incidence of the disease in urban society. The results of an on-going multi-centre trial by the authors are awaited with interest.

Department of Clinical Medicine, Trinity College and St James's Hospital, Dublin, Ireland

Received 27 June 2000

Correspondence to Professor Donald G. Weir, Department of Clinical Medicine, Trinity College Dublin, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland Tel: +353 1 6082100; fax: +353 1 4542043; e-mail: dweir@tcd.ie

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.

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Keywords:

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

© 2001 Lippincott Williams & Wilkins, Inc.