Investigating the effect of a low carbohydrate, high saturated fat diet on concentration levels of markers associated with a leaky gut and the association with glucose homeostasis

Abstract

Abstract Background A high-fat high carbohydrate (HFHC) contributes to the development of prediabetes. This condition precedes the onset of type 2 diabetes (T2D). Hence it has become a therapeutic target to prevent metabolic disorders. Several approaches such as lifestyle modifications that include moderate exercise and dietary intervention have been reported to effectively reverse prediabetes. This study investigated the effect of a low carbohydrate, high saturated fat (LCHSF) diet on glucose homeostasis and concentration levels of markers associated with a leaky gut in male Sprague Dawley rats.Methods The animals (n = 12) ingested a HFHC diet for a period of 20 weeks. After 20 weeks, the prediabetic animals were subdivided into two groups to further investigate the effects of diets for additional 12 weeks. Group 1 was the prediabetic control group (PD) that remained on a HFHC diet and group 2 was the prediabetic group that switched to a LCHSF diet (PD + DI). At the end of 32 weeks, the fecal samples were analyzed to measure the gut microbiota composition of Firmicutes, Bacteroidetes, and Proteobacteria in both animal groups. Furthermore, blood glucose, glycated haemoglobin, serum zonulin, plasma LPS, soluble CD14, tumor necrosis factor-alpha, interleukin-6, C- reactive protein, and intestinal fatty-acid binding protein concentrations were measured.Results In the PD + DI group, there was a significant increase in the Firmicutes levels and a decrease in Bacteroidetes and Proteobacteria compared to PD. Blood glucose and HbA1c concentration were significantly decreased in the PD + DI group in comparison to PD. Zonulin and sCD14 concentrations in the PD + DI group decreased compared to the PD group, while LPS concentrations were similar. A decrease in TNF-α, IL-6, CRP, and IFABP concentrations in the PD + DI group was observed compared to PD.Conclusion Taken together, these results suggest that a LCHSF diet effectively improved glucose homeostasis, gut microbiota composition and beneficially reduced the risk of insulin resistance observed in a prediabetic state.