Investigating the association between diet-induced "leaky gut" and the development of prediabetes.

Chronic consumption of a high-calorie diet compromises the gut microbiota and the integrity of the intestinal wall, which causes translocation of bacterial lipopolysaccharides into the blood. This elicits secretion of pro-inflammatory cytokines, which result in inflammation. However, it has not been investigated how a high-fat high carbohydrate diet affects intestinal permeability and whether or not this plays a role in the development of prediabetes. This study investigated the effects of HFHC diet-induced prediabetes on gut microbiota and intestinal permeability in male Sprague Dawley rats. The animals were randomly assigned into the non-prediabetic group (NPD) and diet-induced prediabetic group (PD) (n=6) for a period of 20 weeks. After 20 weeks, the fecal samples were analyzed to measure the gut microbiota level of Firmicutes, Bacteroidetes, and Proteobacteria in both animal groups. Furthermore, blood glucose, plasma insulin, serum zonulin, plasma LPS, soluble CD14, tumor necrosis factor-alpha, interleukin-6, C-reactive protein, and intestinal fatty-acid binding protein concentrations were measured. The fecal samples revealed that in the PD group, there was a reduction in the Firmicutes levels and an increase in Bacteroidetes and Proteobacteria compared to NPD. Blood glucose and insulin concentration were significantly increased in the PD group by comparison to NPD. Serum zonulin and plasma sCD14 concentrations in the PD group were increased compared to NPD, while plasma LPS concentrations were similar. An increase in plasma TNF-α, IL-6, and CRP concentrations in PD was observed compared to NPD. IFABP, an intracellular protein expressed in the intestine, had increased concentration in PD compared to NPD. Taken together, these results suggest that chronic consumption of the HFHC diet may be associated with the dysregulation of gut microbiota, leading to increased intestinal permeability. Keywords: Pre-diabetes, high-fat high carbohydrate, gut microbiota, zonulin, lipopolysaccharides, intestinal permeability.