Dynamics of Gut Microbiota and Clinical Variables after Ketogenic and Mediterranean Diets in Drug-Naïve Patients with Type 2 Diabetes Mellitus and Obesity

Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is a progressive chronic metabolic disease which has increasingly spread worldwide, enhancing the mortality rate par-ticularly from cardiovascular diseases (CVD). Lifestyle improvement, through diet and physical activity is, together with drug treatment, the cornerstone of T2DM management. The Mediterranean diet (MD), which favours a prevalence of unprocessed vegetable foods and a reduction in red meats and industrial foods, without excluding any food category, is usually recommended. Recently, scientific societies have promoted a very low calories ketogenic diet (VLCKD), a multiphasic protocol which limits carbohydrates and then gradually re-introduces them, with a favorable outcome on body weight and metabolic parameters. Indeed, gut microbiota (GM) modifications have been linked to overweight/obesity and metabolic alterations typical of T2DM. Diet is known to largely affect GM, but only few studies have investigated the effects of VLCKD on GM, especially in T2DM. In this study we have compared anthropometric, biochemical, lifestyle parameters, the quality of life, and the GM of eleven patients with recently diagnosed T2DM and overweight or obesity, randomly assigned to two groups of six and five patients who followed the VLCKD (KETO) or hypocaloric MD (MEDI) respectively; parameters were recorded at baseline (T0) and after two (T2) and three months (T3). The results showed that VLCKD had more significant beneficial effects than MD on an-thropometric parameters, while biochemical improvements did not statistically differ. As for the GM, despite the lack of significant results regarding the alfa and beta diversity, and the Firmicutes/Bacteroidota ratio between the two groups, in KETO group, a significant increase in beneficial microbial taxa such as Verrucomicrobiota phylum with its members Verrucomicro-biae, Verrucomicrobiales, Akkermansiaceae and Akkermansia, Christensenellaceae family, Eu-bacterium spp, and a reduction in microbial taxa previously associated with obesity (Firmicutes and Actinobacteriota) or other diseases (Alistipes) was observed both at T2 and T3. As regards MEDI group, variations were limited to a significant increase of Actinobacteroidota phylum at T2 and T3, and Firmicutes phylum at T3. Moreover, a metagenomic alteration linked to some metabolic pathways was found exclusively in KETO group. In conclusion, both dietary approaches allowed patients to improve their state of health, but VLCKD has shown better results on body composition as well as on GM profile.