Environmental risk factors (excluding tobacco and microorganisms): critical analysis of old and new hypotheses

doi:10.1016/j.bpg.2003.12.005

Best Practice & Research Clinical Gastroenterology

Volume 18, Issue 3, June 2004, Pages 497-508

https://doi.org/10.1016/j.bpg.2003.12.005 Get rights and content

Abstract

The increase in incidence in both ulcerative colitis and Crohn's disease during the 20th century has led to an abundance of different hypotheses on what sort of exposures are responsible. There has been a special focus on dietary factors, as well as on other exposures introduced on a population-based level, including fast food, cola drinks, toothpaste, antibiotics and oral contraceptives. The aim of this review is to critically assess the results from the different observational studies that have investigated these hypotheses, and also to propose research agendas that should be pursued in the future. The conclusion is that infectious exposures and early bacterial colonization, which are associated with better hygiene early in life and that influence immune function, and possibly oral contraceptives, remain the only exposures of interest for future research into the aetiology of ulcerative colitis and Crohn's disease.

Section snippets

Diet

As UC and CD mainly affect the gastrointestinal tract, it is understandable that different dietary exposures have been proposed as the major cause for both diseases. Moreover, the increase in incidence of both diseases in countries like Japan⁶ and South Korea⁷ during the 1990s and evidence from immigration studies⁸ further implicate a westernized diet as an underlying cause. Analysis of the impact of different dietary compounds on outcomes like UC and CD is fraught with methodological

Oral contraceptives

Like margarine and fast food, oral contraceptives are a recent exposure, in this case from the beginning of the 1960s. The increase in incidence, especially of CD, has been hypothesized to be causally related to the exposure of oral contraceptives. Oral contraceptives could also be the underlying reason for the emerging female predominance in adult (but not paediatric) CD.³⁸ However, it is worth pointing out that the increase in incidence in CD in some populations started early in the

Antibiotics

It can be argued that exposure to antibiotics falls within the realms of the chapter on microorganisms and IBD. However, exposure to antibiotics is a relatively new phenomenon and coincides with the emerging epidemic of IBD since the Second World War. It has been argued that this is not mere coincidence but that the correlation over time implies a causal association.⁴⁸ Although, as always in ecological studies, it is tempting to infer such causal association there are strong arguments against

Hygienic factors

Among other things, the 20th century was characterized by greatly improved hygiene as a result of improved access to clean water, less crowded living conditions, non-contaminated food and hygiene products such as toothpaste. Hygiene is therefore the final heading for exposures implicated as aetiological factors for IBD.

Summary

It is somewhat depressing that there is so little knowledge of the underlying causes of the epidemic of IBD during the 20th century. An abundance of poorly conducted case-control studies, with low statistical power and insufficient methodology, have addressed a broad range of potential exposures. These agents are to some extent more characterized by superstition than any in-depth understanding of potential underlying biological mechanisms. There is therefore a need for good studies, preferably

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Crohn disease is an incurable, chronic disease of unknown etiology, which along with ulcerative colitis comprises inflammatory bowel disease (IBD). Crohn disease is characterized by transmural inflammation that can involve any part of the gastrointestinal tract, from mouth to anus, and presentations of the disease vary widely. Although there is no cure for Crohn disease at this time, great advances in medicine and surgery have aided in reducing the symptoms and suffering of these patients. As such, a multidisciplinary team approach to care, including specialized experts in gastroenterology, surgery, and radiology is essential to ensure these patients receive current, appropriate, and high-quality care.
Diet and risk of inflammatory bowel disease
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It has been suggested that microparticles act like antigen transporters from the lumen to the intestinal mucosa. In vitro, complexes formed by antigens and microparticles are powerful stimuli of T lymphocytes and macrophages [83]. One study failed to observe any difference between CD patients and controls with regard to the quantity of food microparticles contained in diet [84].
A better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses.
To review current knowledge on dietary risk factors for inflammatory bowel disease.
The PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease.
Established non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case–control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate).
A diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects.
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Island biogeography effects on microbial evolution may contribute to Crohn's disease
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Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD), involve a poorly understood and complex immune response to both the biota of the human gut and the gut itself. The role of the gut biota in human health has been ill defined and attitudes toward the intestinal flora have ranged from judging them largely irrelevant to declaring them a human organ system. A better way to view the intestinal flora is as a group of evolutionarily self-interested species that form large, potentially interbreeding populations that utilize human beings as a series of semi-isolated habitats, like islands in an archipelago. Here we propose that the imposition of modern sanitation and hygiene standards has drastically attenuated the connection between the “islands” inhabited by the gut flora, and that existing work drawn from evolutionary biology studies of island ecosystems, rather than medicine, predicts that the evolution of gut flora should now be pushed toward limited-dispersion forms of intestinal microorganisms – a proposition borne out by the discovery of so-called “adherent invasive Escherichia coli.” This pathogenic variant of the gut bacterium E. coli clings to and invades the intestinal epithelium and has been implicated in CD. Gut flora and diseases of the gut should arguably be studied as ecology as much as medicine, and treated within this context.
Concordance for IBD among twins compared to ordinary siblings - A Norwegian population-based study
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Citation Excerpt :
Although the concordance rate for many common diseases is higher among MZ than among DZ twins, MZ pairs are often discordant for diseases, which have been attributed to the effect of unique environmental factors. Several studies have provided evidence that environmental factors play an important role in the development of IBD.8 Exposures early in life, such as colonization of the gut,9 breast feeding,10 early infectious diseases,11 and smoking history12,13 may influence the development of IBD later in life.
Comparing the risk to develop concordant disease among twins with inflammatory bowel disease (IBD) to ordinary siblings. Moreover, clinical characteristics of IBD and the association between perinatal factors and IBD, were evaluated.
Patients with IBD, enrolled from an incidence study between 1990 and 1994, and the twins were identified from the Norwegian national birth registry, which was established in 1967.
Eight monozygotic and 16 dizygotic pairs, in which at least one twin reported a positive history of IBD were compared to 84 patients with Crohn's disease (CD) and 87 patients with ulcerative colitis (UC) from the incidence study. The relative risks for concordant disease in monozygotic pairs were estimated to 95.4 (95% CI: 76.3, 114.6) and 49.5 (95% CI: 35.7, 63.3) for CD and UC, respectively. The corresponding risks in dizygotic pairs were 42.4 (95% CI: 29.6, 55.2) and 0.0. Among ordinary siblings of CD and UC the risks for concordance were 22.7 (95% CI: 13.3, 32.1) and 4.6 (95% CI: 0.4, 8.7), respectively.
Stricturing disease was significantly higher in twins with CD compared to incidental cases. The first-born twin in pairs discordant for disease, 12 out of 19 (63.2%), tended to be affected by IBD (p = 0.10).
Genetic factors influence the development of IBD and fibrostenotic disease in CD. The increased risk for concordant disease among dizygotic twins compared to ordinary siblings, at least in CD, might underscore the importance of shared environment in utero or in childhood.

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4Environmental risk factors (excluding tobacco and microorganisms): critical analysis of old and new hypotheses

Abstract

Section snippets

Diet

Oral contraceptives

Antibiotics

Hygienic factors

Summary

American Journal of Clinical Nutrition

Journal of American Diet Association

American Journal of Gastroenterology

Gastroenterology

Gastroenterology

Lancet

Lancet

Journal of Clinical Epidemiology

Historical review

Crohn's disease in Dublin in the latter half of the nineteenth century

Ireland Journal of Medical Science

Geographic variation in the incidence of and mortality from inflammatory bowel disease

Diseases of the Colon and Rectum

Familial occurrence of inflammatory bowel disease

New England Journal of Medicine

Chronic interstitial enteritis

British Journal of Medicine

Incidence and prevalence of ulcerative colitis in the Songpa–Kangdong District, Seoul, Korea, 1986–1997

Journal of Gastroenterology and Hepatology

Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire

Gut

Crohn's disease and ulcerative colitis. A review of dietary studies with emphasis on methodologic aspects

Scandinavian Journal of Gastroenterology

Nutritional factors in inflammatory bowel disease

European Journal of Gastroenterology and Hepatology

Geographic temporal variations of sugar and margarine consumption in relation to Crohn's disease

Digestion

Consumption of refined sugar by patients with Crohn's disease, ulcerative colitis, or irritable bowel syndrome

Scandinavian Journal of Gastroenterology

Increased sugar consumption in Crohn's disease

Digestion

Modern life in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors

European Journal of Gastroenterology and Hepatology

A review of associations between Crohn's disease and consumption of sugars

Euroapean Journal of Clinical Nutrition

Smoking and sugar intake are separate but interactive risk factors in Crohn's disease

Gut

Smoking, sugar, and inflammatory bowel disease

British Medical Journal (Clinical Research Edition)

Pre-illness dietary factors in inflammatory bowel disease

Gut

Diet and Crohn's disease: characteristics of the pre-illness diet

British Medical Journal

Diet and inflammatory bowel disease: a case-control study

Epidemiology

The young pretender (correspondence)

Lancet

Dietary fads and gut mysteries versus nutrition with a grain of common sense

Canadian Journal of Gastroenterology

IS900 PCR to detect Mycobacterium paratuberculosis in retail supplies of whole pasteurized cows' milk in England and Wales

Applied and Environmental Microbiology

4
Environmental risk factors (excluding tobacco and microorganisms): critical analysis of old and new hypotheses