Intestinal Alkaline Phosphatase Interaction Gut Model.

Abstract

High fat Western diet (WD) is known to alter the composition of gut microbiota causing the release of lipopolysaccharide (LPS) (Cani et al. 2007). LPS is a TLR4 ligand, produced by Gram-negative bacteria, and is a potent inducer of various inflammatory cytokines. Inflammation in the gut can promote leaky gut syndrome which results in the translocation of LPS from the gut to circulation. The resulting leakage activates pro-inflammatory cytokines and alters macrophage polarization (Pelegrin and Surprenant 2009). This systemic inflammation can aggravate various diseases such as diabetes, atherosclerosis and chronic liver disease. Intestinal Alkaline Phosphatase (IAP) dephosphorylates LPS and renders it inactive, subsequently reducing leaky gut phenomenon. Informed by mouse model data, we developed an ordinary differential equation model to dynamically model the effect of diet on circulating LPS levels. The model allows for better understanding of systemic risk factors and for exploration of potential treatment using IAP-based interventions.