Nutrition, Gut Microbiota and Immunity: Therapeutic Targets for IBD

J. D. Lewis, F. M. Ruemmele, G. D. Wu

• Publisher: S. Karger
• Year: 2014
• ISBN:
  9783318026702
• Topic: Medicina
• Subtopic: Gastroenterología y hepatología

Inflammatory Bowel Disease (IBD) is a chronic debilitating disorder that occurs at any age and in populations around the world. Its pathogenesis is believed to involve a combination of genetic susceptibility, immune and external environmental factors, including the gut microbiota. Changing factors such as diet and the human gut microbiota may thus be a viable alternative to suppressing the innate and adaptive immune responses. The book at hand starts with a summary of the current understanding of the epidemiology and biologic underpinnings that manifest as IBD. Next, the gut microbiota, its function, and how it may interact with nutritional status in perpetuating IBD are looked at, followed by discussions on the potential for manipulation of the gut microbiota through the use of prebiotics, probiotics, antibiotics, and fecal transplantation. Chapters on the current role of and future prospects for nutritional interventions in the management of IBD complete the topics presented.

Pathogenesis of IBD

Lewis JD, Ruemmele FM, Wu GD (eds): Nutrition, Gut Microbiota and Immunity: Therapeutic Targets for IBD. Nestlé Nutr Inst Workshop Ser, vol 79, pp 1-18, (DOI: 10.1159/000360664) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2014

______________________

A Review of the Epidemiology of Inflammatory Bowel Disease with a Focus on Diet, Infections and Antibiotic Exposure

James D. Lewis

Department of Medicine and Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

______________________

Abstract

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic debilitating diseases that occur in populations around the world. The underlying etiology is thought to be multifactorial. There is a well-defined genetic contribution to the diseases, but this does not fully explain the epidemiology. Environmental factors, including the composition of the gut microbiota, are also important. There is wide geographic variability in the incidence and prevalence of IBD. High incidence rates have been observed in the United Kingdom, Northern Europe, Canada, and the United States. Globally, there is evidence of increasing incidence of CD and UC over time. The rising incidence of IBD in Western countries has generally predated that in developing nations, supporting the hypothesis that ‘Westernization’ of our lifestyle has led to the increased incidence of IBD. Smoking, antibiotic use, and diet are potentially reversible risk factors for IBD. Recommendations to avoid smoking are appropriate for all people, for numerous reasons. Antibiotic use should be limited to appropriate indications, a recommendation that too is appropriate for all populations. Detangling the relationship between diet, the gut micro-biome and IBD raises the potential to reduce the incidence of IBD through dietary modification, an approach that might be considered among those at the highest risk.

© 2014 Nestec Ltd., Vevey/S. Karger AG, Basel

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic debilitating diseases that occur in populations around the world. The diseases can manifest at any age, and therefore represent a clinical challenge for pediatricians, internists, family practitioners, and sur-geons. The underling etiology is thought to be multifactorial. There is a well-defined genetic contribution to the diseases, but this does not fully explain the epidemiology. Environmental factors, including the composition of the gut microbiota, are also important. This review will focus on the relationship between IBD and other environmental factors, such as diet, infections, and medications.

Incidence and Prevalence of IBD

Studies of the incidence and prevalence of IBD were recently summarized in a review by Cosnes et al. [1]. Within North America, the prevalence of CD is approximately 44-201 per 100,000, with increasing incidence until approximately age 30. Similarly, estimates of the prevalence of UC range from 37.5 to 238 per 100,000, with incidence increasing until approximately age 40. Although early research suggested a bimodal pattern of incidence with a second peak later in life, this has not been consistently observed.

There is wide geographic variability in the incidence and prevalence of IBD. High incidence rates have been observed in the United Kingdom, Northern Europe, Canada, and the United States. The incidence of IBD is generally lower in the Asia-Pacific region, with the exception of Australia [2]. In many regions, there is evidence of increased incidence and prevalence as one moves further from the equator [3]. Similar patterns have been seen with other immune mediated diseases such as psoriasis and multiple sclerosis [4, 5].

Globally, there is evidence of increasing incidence of CD and UC over time [6]. Furthermore, the rising incidence of IBD in Western countries has generally predated that in developing nations. In general, the incidence of UC has risen before that of CD within any given area. For example, in 2012, the ratio of UC to CD in Asia was 2.0, while in Australia it was 0.5 [2].

The rising incidence of UC and CD across the world, but earlier in developed nations, has contributed to the hypothesis that ‘westernization’ of our lifestyle has led to the increased incidence of IBD. Before focusing on the specific evidence that supports an association between a Western lifestyle and the development of IBD, it is important to consider possible alternative explanations for the geographic patterns that have emerged. The most obvious alternative explanation is that improved access to healthcare and improved diagnostic tools led to more frequent diagnosis of IBD. It is possible that some patients with mild IBD who previously went undiagnosed throughout their entire life are now diagnosed because of greater availability of colonoscopy and cross-sectional imaging modalities. Increased awareness of IBD by clinicians could also contribute to rising incidence rates. Likewise, cultural norms may have evolved in some re-gions, such that there is greater willingness to discuss one's bowel symptoms. Each of these could contribute to an apparent increased incidence and prevalence even if there were truly no change in the epidemiology of these diseases.

Arguing against detection bias is the observation that incidence rates of numerous other immune-mediated diseases have also increased in a pattern similar to IBD [7-10]. Diseases such as asthma and psoriasis are diagnosed without the need for invasive or expensive tests. Given the frequent co-occurrence of immunologic diseases, it seems more likely that one or more environmental factors have contributed to the rising incidence rates of all of these diseases [11, 12].

This review will focus on several hypotheses related to the changing epidemiology of IBD, with a specific focus on environmental factors. Although the human gut microbiome can be considered an environmental factor, this will not be addressed in detail in this review, as it is the focus of another chapter in this book. Likewise, the important contribution of genetics to the epidemiology of IBD will not be discussed in detail since this will also be covered in another chapter.

Emigration

Some of the regional variation in incidence and prevalence of IBD is likely due to genetic factors. Increased access to care and diagnostic tests could also lead to higher incidence rates in more industrially developed nations. A recent systematic review demonstrated significantly higher incidence rates for both CD and UC among urban populations [13]. The strength of association was greater for CD than UC, although there was significant heterogeneity in each analysis without an obvious explanation. In addition to greater access to healthcare, environmental factors such as diet, pollution, climate, hygiene, and crowding may also contribute to these differences, and would be associated with urban residence.

Studies of people who move between regions of differing IBD incidence and prevalence provide an opportunity to assess the impact of environmental factors on the risk of developing IBD. Several investigators have examined the incidence of IBD within Israel because Jews residing in Western countries are known to have an increased incidence of IBD. In early studies from Israel, immigrants to Israel had higher incidence rates than did Israeli-born populations [14-16]. However, by late 1980s, the incidence and prevalence of CD was comparable among Jews in southern Israel regardless of whether the patient or the patient's father was born in Israel, Asia, Africa, Europe or America [17]. In contrast, the prevalence was much lower among Arab Israelis, which could be due to genetic or environmental differences since during this time period the Israeli Bedouin population led a lifestyle ‘more characteristic of Third World countries’ [17].

More recent data from Sweden suggest that the incidence of IBD is generally lower in first-generation immigrants, but by the second generation is comparable to that of the Swedish population [18]. Taking advantage of a unique population-based registry, Li et al. [18] observed that the incidence of CD was significantly lower among all first-generation immigrants, and that this was most evident among immigrants from Africa (SIR 0.54, 95% CI: 0.37-0.77), Asia (SIR 0.64, 95% CI: 0.54-0.74), Baltic countries (SIR 0.45, 95% CI: 0.23-0.79) and Latin America (SIR 0.43, 95% CI: 0.28-0.63). Only among those from Latin America was there a significantly lower incidence rate of CD among second-generation immigrants. Generally, similar results were observed for UC, with second generation incidence rates for most immigrants being similar to that of the Swedish population, while second-generation immigrants from southern and Eastern Europe continued to have lower incidence rates. Notably, if both parents were immigrants from the same country, the second generation continued to have a lower incidence of CD. Whether this is due to greater retention of lifestyle customs from the parents’ native land o...