Relationship(s) between obesity and inflammatory bowel diseases: possible intertwined pathogenic mechanisms

Abstract

The inflammatory bowel diseases, Crohn's and ulcerative colitis have increased in incidence and prevalence from the mid-eighteen to the late nineteen centuries. From then to the current twenty-first century there has been a more rapid expansion of these disease to areas previously experiencing low rates. This latter expansion coincides with the current obesity pandemic which also began toward the end of the last century. Although the two diseases have radically different frequencies, there are interesting links between them. Four areas link the diseases. On an epidemiological level, IBD tends to follow a north-south gradient raising the importance of vitamin D in protection. Obesity has very weak relationship with latitude, but both diseases follow adult lactase distributions colliding in this plane. Is it possible that obesity (a low vitamin D condition with questionable response to supplements) reduces effects in IBD? On a pathogenic level, pro-inflammatory processes mark both IBD and obesity. The similarity raises the question of whether obesity could facilitate the development of IBD. Features of the metabolic syndrome occur in both, with or without obesity in IBD. The fourth interaction between the two diseases is the apparent effect of obesity on the course of IBD. There are suggestions that obesity may reduce the efficacy of biologic agents. Yet there is some suggestion also that obesity may reduce the need for hospitalization and surgery. The apparent co-expansion of both obesity and IBD suggests similar environmental changes may be involved in the promotion of both.

Keywords: Clinical; Inflammatory bowel diseases; Obesity; Pathogenic relationships.

Fig. 1

Pathogenic contributions associated with obesity are shown figure based on and modified from reference [46]. The primary drivers of host pro-inflammatory response originate from adipokines produced from visceral and subcutaneous fat. Reduced levels of adiponectin play a permissive role in the release of pro-inflammatory cytokines (TNFα tumor necrosis factor alpha, CRP C-reactive protein, IL-6 interleukin-6, vascular cell adhesion molecule-1-VCAM 1 and monocyte chemoattractant protein-1-MCP-1) [–78, 80, 83]. Insulin resistance is promoted also by the interaction of TNFα and insulin receptor which decreases tyrosine kinase [75]. Insulin resistance promotes oxidative stress which also can impact on intestinal bacteria. In addition, alterations in the intestinal microbiome contribute to dysbiosis as well as to altered intestinal permeability which then, in turn, contributes to promoting the pro-inflammatory state [84, 85]. Low-grade inflammation facilitates diseases like inflammatory bowel diseases