Characteristics of the Gut Microbiota and Metabolism in Patients with Unclassified Diabetes in Adults: A Case‒Control Study

Abstract Background The classification of diabetes has become increasingly intricate. In 2019, the World Health Organization (WHO) introduced a new category called "unclassified diabetes" to address this complexity. Our study, employing a multiomics approach, aimed to delineate the distinct gut microbiota and metabolic characteristics in individuals under the age of 30 with unclassified diabetes, thus shedding light on the underlying pathophysiological mechanisms involved. Methods This age- and sex-matched case‒control study involved 18 patients with unclassified diabetes, 18 patients with classic type 1 diabetes, 13 patients with type 2 diabetes, and 18 healthy individuals. Metagenomics facilitated the profiling of the gut microbiota, while untargeted liquid chromatography‒mass spectrometry was used to quantify the serum lipids and metabolites. Results Our findings revealed a unique gut microbiota composition in unclassified diabetes patients, marked by a depletion of Butyrivibrio proteoclasticus and Clostridium and an increase in Ruminococcus torques and Lachnospiraceae bacterium 8_1_57FAA. Comparative analysis identified exclusive bacteria, serum metabolites, and clinical parameter modules within the unclassified diabetes cohort. Notably, the gut microbiota structure of patients with unclassified diabetes resembled that of type 2 diabetes patients, especially in terms of disrupted lipid and branched-chain amino acid metabolism. Conclusions Despite sharing certain metabolic features with type 2 diabetes, unclassified diabetes presents unique features. The distinct microbiota and metabolites in unclassified diabetes patients suggest a significant role in modulating glucose, lipid, and amino acid metabolism, potentially influencing disease progression. Further longitudinal studies are essential to explore therapeutic strategies targeting the gut microbiota and metabolites to modify the disease trajectory.