Review: Influence of Environmental Factors in Inflammatory Bowel Disease

Environmental factors play a prominent role in the pathogenesis of inflammatory bowel disease (IBD), according to accumulating epidemiologic data. Such factors include behaviors that increase risk at an individual level, such as diet and those that affect entire populations, such as urbanization.

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In Gastroenterology & Hepatology (NY), Amar Vedamurthy, MD, MS, hospitalist within the Department of Medicine at Massachusetts General Hospital, and Ashwin N. Ananthakrishnan, MBBS, MPH, director of the Mass General Crohn's and Colitis Center, recently reviewed the literature on environmental factors that influence the development and outcomes of Crohn's disease (CD) and ulcerative colitis (UC).

Smoking

Gastroenterologists have known for decades that smoking influences the risk of IBD. Chronic smoke exposure can change immune responses and the composition of the gut microbiome, and it can predispose patients to intestinal inflammation by altering the composition and integrity of the epithelial mucous membrane.

Both current and former smokers are at increased risk of CD. Current smokers with CD have increased need for medical therapy, surgery and second surgery, and they are at higher risk of disease flares including flares after surgery.

In fascinating contrast, current smokers with UC have a milder disease course than nonsmokers, including less need for surgery. In fact, smoking cessation by patients with UC is frequently associated with relapse.

Diet

Diet is considered an important environmental factor in the pathogenesis of IBD. For example:

• Higher intake of dietary fiber, especially when obtained from vegetables and fruits, has been associated with decreased incidence of CD
• In a past study, higher dietary intake of omega-3 fatty acids was associated with a lower risk of UC, whereas a diet high in omega-6 fatty acids was linked to increased risk of UC
• High animal protein intake may increase risk of UC while intake of fish may be inversely related

Most patients diagnosed with IBD come to find that diet affects their symptoms. However, there is limited data on the ability of dietary modification to achieve sustained disease remission.

Antibiotics

The use of antibiotics, which alters the gut microbiome, has been examined in multiple epidemiologic studies of IBD. For example:

• In population-level research, exposure to antibiotics within the first year of life was tied to increased incidence of IBD, particularly CD
• A meta-analysis representing most antibiotic groups showed a marked increase in the risk of CD in children
• Adults with newly diagnosed IBD were more likely than controls to have been prescribed antibiotics two to five years prior to diagnosis

Fecal microbiota transplantation and microbiome manipulation using antibiotics have shown promise in the treatment of IBD, but the data are still inadequate to support them as primary therapy.

Geographic Factors

The gap between Western and Eastern countries in the prevalence of IBD is narrowing, which is probably largely attributable to urbanization, westernization of diet and improvement in hygiene in Eastern countries.

People living in urban areas have a higher incidence of IBD than those in rural areas. The oft-cited hygiene hypothesis may be explanatory: Urban settings have fewer influences, such as exposure to animals and pets, that protect against an immune response skewed toward autoimmunity and atopy.

Northern latitudes are associated with a higher risk of IBD than southern latitudes, possibly because of low exposure to sunlight and consequent deficiency of vitamin D, which is known to modulate intestinal inflammation.

Other Factors

There are a multitude of additional factors that influence the development of CD and UC. For example:

• Appendectomy is reportedly inversely associated with the risk of UC, perhaps because T cells in the appendix may act as a "priming site" in the pathogenesis of UC
• Breastfeeding was inversely associated with the child's risk of CD or UC in the largest meta-analysis to date
• Depression and psychosocial stress may increase the risk of incident IBD and relapse, although evidence is mixed
• Exercise, if regular and vigorous, may be associated with a lower risk of CD and reduce the risk of active disease in patients with CD or UC
• Nonsteroidal anti-inflammatory drugs have been implicated in the development and relapse of IBD in a growing number of studies

Potential for Future Research

The latest research provides key insights into how environmental factors affect susceptibility to IBD, but few studies have examined whether modifying those factors changes the disease course. Continued research into environmental influences on IBD could lead to new strategies for disease prevention and treatment.

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