IntroductionThe gut microbiota (GM) dysbiosis is one of the causal factors for the progression of different chronic metabolic diseases, including type 2 diabetes mellitus (T2D). Understanding the basis that laid this association may lead to developing new therapeutic strategies for preventing and treating T2D, such as probiotics, prebiotics, and fecal microbiota transplants. It may also help identify potential early detection biomarkers and develop personalized interventions based on an individual’s gut microbiota profile. Here, we explore how supervised Machine Learning (ML) methods help to distinguish taxa for individuals with prediabetes (prediabetes) or T2D.MethodsTo this aim, we analyzed the GM profile (16s rRNA gene sequencing) in a cohort of 410 Mexican naïve patients stratified into normoglycemic, prediabetes, and T2D individuals. Then, we compared six different ML algorithms and found that Random Forest had the highest predictive performance in classifying T2D and prediabetes patients versus controls.ResultsWe identified a set of taxa for predicting patients with T2D compared to normoglycemic individuals, includingAllisonella, Slackia, Ruminococus_2, Megaspgaera, Escherichia/Shigella, and Prevotella, among them. Besides, we concluded thatAnaerostipes, Intestinibacter, Prevotella_9, Blautia, Granulicatella, andVeillonellawere the relevant genus in patients with prediabetes compared to normoglycemic subjects.DiscussionThese findings allow us to postulate that GM is a distinctive signature in prediabetes and T2D patients during the development and progression of the disease. Our study highlights the role of GM and opens a window toward the rational design of new preventive and personalized strategies against the control of this disease.