| Summary: | 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<sup>®</sup>, 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<sup>®</sup>), inoculated with pre-diabetic microbiota. After treatment with Eriomin<sup>®</sup> 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<sup>®</sup> plus metformin stimulated the growth of <i>Bacteroides</i> and <i>Subdoligranulum</i> genera. <i>Bacteroides</i> 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, <i>Subdoligranulum</i> species are associated with better host glycemic metabolism. In conclusion, Eriomin<sup>®</sup> associated with metformin improved the composition and metabolism of the intestinal microbiota, suggesting a potential use in pre-diabetes therapy.
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