The effects of sodium butyrate and high-performance inulin supplementation on the promotion of gut bacterium Akkermansia muciniphila growth and alterations in miR-375 and KLF5 expression in type 2 diabetic patients: A randomized, double-blind, placebo-controlled trial

Introduction: The aim of this study is to evaluate the effect of sodium butyrate and High-Performance (HP) inulin supplementation on the promotion of gut bacterium Akkermansia muciniphila growth and alterations in microRNA-375 and Krüppel-like factor 5 (KLF5) expression in patients with T2D. Methods: In this clinical trial, 60 patients with T2D were recruited and randomly allocated into four groups of equal size to receive 600 mg/day sodium butyrate (Group A), 10 g/day inulin powder (Group B), concomitant use of inulin and sodium butyrate (Group C), or placebo (Group D). Blood and stool samples were collected pre- and post-intervention. Quantitative real-time PCR analysis targeting the 16S rRNA gene of A.muciniphila was performed to determine its presence in the patient's stool. In addition, we assessed the KLF5 mRNA expression and the plasmatic level of the microRNA-375 before and after the intervention. Results: The results showed that A. muciniphila percent change increased significantly after supplementation with HP inulin (p = 0.017) and butyrate (p = 0.036). Also, supplementation with HP inulin significantly decreased the KLF5 fold change after intervention (fold change 0.42 ± 0.15, p = 0.037). In particular, in comparison to the placebo group, an increased expression of miR-375 was seen after butyrate and butyrate+ inulin supplementation (P = 0.003 and P = 0.007 respectively). Conclusions: We concluded that inulin and butyrate may potentially promote gut health and can be considered as novel therapeutic approache for the prevention and control of diabetes.