The Effects of a Ketogenic Diet on the Gut Microbiota of Non-Alcoholic Liver Disease Patients with Diabetes Mellitus Type 2

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease and arises from excessive fat accumulation in the form of triglycerides. It is projected to be the most frequent indication for liver transplantation by the year 2030. There is an evolving body of evidence that NAFLD is a multisystem disease, that influences extrahepatic regulatory pathways and organ systems. NAFLD dramatically increases the risk of cardiovascular disease and chronic kidney disease. The pathogenesis of NAFLD is highly complex and poorly understood but is thought to be strongly associated with fat and glucose metabolism. Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic diseases and is linked to the genesis of NAFLD. Further, liver fat accumulation in NAFLD doubles the risk of developing T2DM. Ketone body have been shown to improve NAFLD. In recent years, the ketogenic diet has been having gained popularity as a weight-loss and dietary approach. Moreover, the ketogenic diet is hypothesized to have an impact on T2DM and NAFLD. Furthermore, novel genetic studies such as high-throughput genetic sequencing allow for the analysis of the gut microbiota. The prior suggests that the gut microbiota plays a key role in the events leading to NAFLD and T2DM. Lastly, the ketogenic diet is thought to have a beneficial effect on the composition of the gut microbiota. Aim: To investigate the effects of a ketogenic diet on the microbiota of non-alcoholic liver disease patients with Type 2 Diabetes Mellitus in the scientific literature. Methods: A literature review was conducted to investigate and explore the effects of ketogenic diets on the microbiota of NAFLD patients with Type 2 Diabetes Mellitus. Conclusions: The gut microbiota of NAFLD patients is dominated by Firmicutes and Proteobacteria with a concurrent reduction in Bacteroidetes. The progression of NAFLD is linked to the diversity of the gut microbiota and each stage of the disease has a specific gut microbiome composition. T2DM patients exhibit a gut microbiota profile with high levels of lipopolysaccharides, which is related to the generation of inflammation and insulin resistance. Ketogenic diets have shown a potential in reducing liver fat content, and visceral fat content and in improving insulin resistance, but the evidence is based on small sample size studies and occurs only in short-term interventions. Comparing conventional weight loss diets, the effect of ketogenic diets on glycemic control in T2DM is inconclusive with some studies showing that there is a significantly higher impact on glycemic control, while other studies indicated no significant difference between ketogenic diets and conventional weight loss diets.