Impact of Ketogenic and Mediterranean Diets on Gut Microbiota Profile and Clinical Status in Drug-Naïve Patients with Diabesity: a 12-Month Follow-up

Due to its complexity, the treatment of T2DM requires a multidimensional, patient-centered approach that includes lifestyle improvements through dietary interventions and physical activity. Gut microbiota (GM) alterations have been linked to obesity and metabolic alterations typical of T2DM and is significantly modulated by diet. However, few studies have evaluated the effects on the GM of a very low-calorie ketogenic diet (VLCKD), recently included as an effective therapeutic option, in addition to the Mediterranean diet (MD), in patients with T2DM, especially in the mid-term and long-term. The present longitudinal study is aimed at evaluating the mid-term (up to six months) and long-term (up to 12 months) impact of the VLCKD (on KETO cohort, which shifted from the VLCKD to a MD after two months of NI) and Mediterranean (on MEDI cohort) dietary patterns on the GM and on the anthropometric, clinical and metabolic parameters of 11 patients with diabesity. This study extends previously published results evaluating the short-term (three months) impact on the same patients. Analyses were performed at six (T6) and twelve months (T12) of NI, by comparing data prospectively and with baseline (T0). The GM analysis was performed through Next Generation Sequencing. Improvement in metabolic and clinical parameters were more pronounced in the KETO group at T6, particularly for Body Mass Index (-5.8 vs -1.7 kg/m2; p=0.006) and Waist Circumference (-15.9 vs -5.2 cm; p=0.011). At T6, a significant improvement in HbA1c (6.7% vs 5.5% p=0.02) and triglyceride (158 vs 95 mg/dl p=0.04) values compared to T0 was observed only in the KETO group, which maintained the results achieved at T3. The VLCKD-MD had a more beneficial impact than MD on the GM phenotype. The more positive modulatory effect was observed especially up to the sixth month of the NI in KETO, due to the progressive increase in bacterial markers of human health. After the sixth month, most markers of human health decreased and were no longer significantly increased compared with baseline. Among them, the Verrucomicrobiota phylum was identified as the main biomarker in KETO, together with its members Verrucomicrobiae, Akkermansiaceae, Verrucomicrobiales and Akkermansia at T6 compared with baseline. Both dietary approaches allowed patients to improve their health status, but VLCKD, in support of the MD, has shown greater improvements on anthropometric and metabolic parameters, as well as on GM profile, especially up to T6 of NI.