Obesity-associated cancer risk: the role of intestinal microbiota in the etiology of the host proinflammatory state

Obesity increases the risks of many cancers. One important mechanism behind this association is the obesity-associated proinflammatory state. Although the composition of the intestinal microbiome undoubtedly can contribute to the proinflammatory state, perhaps the most important aspect of host-microbiome interactions is host exposure to components of intestinal bacteria that stimulate inflammatory reactions. Systemic exposures to intestinal bacteria can be modulated by dietary factors through altering both the composition of the intestinal microbiota and the absorption of bacterial products from the intestinal lumen. In particular, high-fat and high-energy diets have been shown to facilitate absorption of bacterial lipopolysaccharide (LPS) from intestinal bacteria. Biomarkers of bacterial exposures that have been measured in blood include LPS-binding protein, sCD14, fatty acids characteristic of intestinal bacteria, and immunoglobulins specific for bacterial LPS and flagellin. The optimal strategies to reduce these proinflammatory exposures, whether by altering diet composition, avoiding a positive energy balance, or reducing adipose stores, likely differ in each individual. Biomarkers that assess systemic bacterial exposures therefore should be useful to (1) optimize and personalize preventive approaches for individuals and groups with specific characteristics and to (2) gain insight into the possible mechanisms involved with different preventive approaches.