Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases

Abstract

The incidence of inflammatory bowel diseases (IBD), as well as other inflammatory conditions, has dramatically increased over the past half century. While many studies have shown that IBD exhibits a genetic component via genome-wide association studies, genetic drift alone cannot account for this increase, and other factors, such as those found in the environment must play a role, suggesting a "multiple hit" phenomenon that precipitates disease. One major environmental factor, dietary intake, has shifted to a high fat, high carbohydrate Western-type diet in developing nations, nearly in direct correlation with the increasing incidence of IBD. Recent evidence suggests that specific changes in dietary intake have led to a shift in the composite human gut microbiota, resulting in the emergence of pathobionts that can thrive under specific conditions. In the genetically susceptible host, the emerging pathobionts can lead to increasing incidence and severity of IBD and other inflammatory disorders. Since the gut microbiota is plastic and responds to dietary modulations, the use of probiotics, prebiotics, and/or dietary alterations are all intriguing complementary therapeutic approaches to alleviate IBD symptoms. However, the interactions are complex and it is unlikely that a one-size-fits all approach can be utilized across all populations affected by IBD. Exploration into and thoroughly understanding the interactions between host and microbes, primarily in the genetically susceptible host, will help define strategies that can be tailored to an individual as we move towards an era of personalized medicine to treat IBD.

Fig. 1

Intake of Western high fat-high carbohydrate diet promotes expansion of pathobionts in the GI tract, resulting in decreased abundance of commensals. Metabolism of the emerging pathobionts leads to increased host exposure to detrimental bacterial products (i.e., H₂S) and reduced exposure to beneficial products, such as short chain fatty acids (SCFAs). This results in increased immunogenic antigen exposure, prompting inflammatory cytokine production of both antigen-presenting cells (i.e., IL-12p40) and T cells (i.e., IFN-gamma) that increase intestinal inflammation

Fig. 2

Microbiota-centric therapeutic strategies, including prebiotics, probiotics, or dietary modulation can promote an increase in short chain fatty acid (SCFA) production even in the context of a Western diet. These therapies may restore commensal microbiota and diminish pathobionts. The therapeutic strategies may restore immune balance, promoting anti-inflammatory properties (such as T-regulatory cell function) leading to a decrease of intestinal inflammation in the genetically-susceptible host