Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

Abstract

Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15-40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

Conflict of interest statement

Competing interests statement

W.J.S. has received consulting fees from Abbvie, Janssen Biotech, Prometheus Laboratories and UCB Pharma, research grants from Abbvie, Janssen Pharmaceutical Research & Development and UCB Pharma, and payments for lectures or speakers bureau from Abbvie, Janssen Pharmaceutical Research & Development. S.S., P.S.D., A.Z. and S.R. declare no competing interests.

Figures

Figure 1. Association between premorbid obesity, waist–hip ratio and weight gain since age 18 years and IBD risk

Data from the Nurses’ Health Cohort showing the relationship between premorbid obesity at 18 years of age, waist–hip ratio and weight gain since age 18 years on the risk of developing Crohn’s disease and ulcerative colitis.

Figure 2. Postulated pathogenesis and feedback loop between visceral adipose tissue and intestinal inflammation in IBD

In patients with IBD, the T-cell compartment shifts from a homeostatic regulatory environment consisting of M2 macrophages, natural killer cells and CD4+ Treg cells toward a pro-inflammatory environment characterized by M1 macrophages, CD4+ TH1 and CD8+ cytotoxic subtypes. Leptin, a member of the IL-6 protein family, is produced by adipocytes in proportion to fat mass. Leptin increases synthesis of pro-inflammatory cytokines in monocytes and macrophages, and is involved in T-cell-mediated immune responses. Adiponectin, produced by adipocytes in an inverse proportion to fat mass, functions as an insulin sensitizer and anti-inflammatory adipokine in patients who do not have IBD. However, in IBD, and in particular in Crohn’s disease, evidence supports its role as a pro-inflammatory adipokine that results in increased cytokine secretion and epithelial cell proliferation. Macrophages and monocytes are the main source of resistin, the expression of which is induced by pro-inflammatory cytokines (IL-1, IL-6 and TNF), and circulating levels correlate with acute-phase reactants (C-reactive protein, CRP). Resistin can promote expression of TNF and IL-6. Evidence from the past decade has demonstrated the existence of an adipose-tissue–colonic-mucosa feedback loop, in which preadipocytes release IL-17A in response to substance P; the colonic mucosa from these individuals shows an increase in IL-17A receptors. Obesity and a high-fat diet, as well as transmural inflammation in Crohn’s disease, results in impaired mucosal barrier function through alterations in tight-junction proteins, thereby promoting bacterial translocation. TLR, Toll-like receptor.