Exploring the Association between Citrus Nutraceutical Eriocitrin and Metformin for Improving Pre-Diabetes in a Dynamic Microbiome Model

Abstract

Pre-diabetes is recognized as an altered metabolic state, which precedes type 2 diabetes, and it is associated with great dysfunction of the intestinal microbiota, known as dysbiosis. Natural compounds, capable of reducing blood glucose without side effects and with a beneficial effect on the microbiota, have been studied as substitutes or adjuvants to conventional hypoglycemic agents, such as metformin. In this work, the effect of the nutraceutical Eriomin®, a mixture of citrus flavonoids (eriocitrin, hesperidin, naringin, and didymin), which reduces glycemia and increases glucagon-like peptide-1 (GLP-1) in pre-diabetic patients, was tested in the Simulator of Human Intestinal Microbial Ecosystem (SHIME®), inoculated with pre-diabetic microbiota. After treatment with Eriomin® plus metformin, a significant increase in acetate and butyrate production was observed. Furthermore, sequencing of the 16S rRNA gene of the microorganisms showed that Eriomin® plus metformin stimulated the growth of Bacteroides and Subdoligranulum genera. Bacteroides are the largest fraction of the intestinal microbiota and are potential colonizers of the colon, with some species producing acetic and propionic fatty acids. In addition, Subdoligranulum species are associated with better host glycemic metabolism. In conclusion, Eriomin® associated with metformin improved the composition and metabolism of the intestinal microbiota, suggesting a potential use in pre-diabetes therapy.