Correlation Between Gut Microbiota and Pancreatic Β-Cell Function in Diabetic Patients

The gut microbiota plays a crucial role in digestion, metabolism, nutrition, and immune regulation in the human body. In recent years, numerous studies have indicated that the gut microbiota and its metabolites are closely associated with metabolic diseases, including obesity, non-alcoholic fatty liver disease, and diabetes. China has rapidly entered an aging society, where aging is a major risk factor for abnormal glucose metabolism, manifested by decreased pancreatic function and increased insulin resistance. Concurrently, as the body ages, the composition of the gut microbiota also undergoes age-related changes, such as reduced microbial diversity, increased inter-individual variability, and a downregulation of the beneficial/harmful bacteria ratio. Therefore, direct modulation of the gut microbiota could become a potential therapeutic target for age-related metabolic diseases. Currently, some preclinical studies have transplanted fecal microbiota from young mice to aged mice to explore the improvement of age-related phenotypes, such as cognitive impairment, decreased immunity, and chronic inflammation.

The regulation of the gut microbiota is susceptible to changes caused by various factors, including age, diet, antibiotics, and psychological stress. Although mice and humans share high genetic homology, differences in diet structure, body size, and metabolic processes can result in significant diversity and compositional differences in their gut microbiota. Research indicates that the core microbiota of the mouse gut consists of 4 genera, while 90% of the European population comprises 9 genera, highlighting the differences in genus or species richness between mouse and human gut microbiota. Preliminary research by our group has shown that transplanting fecal microbiota from young mice to aged mice can increase postprandial plasma insulin levels in aged mice, suggesting that the restoration of gut microbiota diversity may be involved in age-related glucose metabolism abnormalities. However, due to interspecies differences in the gut microbiota, whether the differential microbiota between elderly and young humans can improve age-related glucose metabolism abnormalities remains to be explored.

Despite the abundance of human gut microbiota composition data in public databases, differences in sequencing methods, DNA extraction from specimens, and the nationality of subjects prevent standardization and integration of these data. Additionally, traditional 16s-rRNA sequencing methods lack sufficient precision in microbial classification and cannot annotate gene functions. These limitations have resulted in many studies on gut microbiota remaining at the level of exploring correlations with diseases, without establishing causality. The development of metagenomic sequencing technology can extend the definition of the human core gut microbiota to the species level and accurately annotate their gene functions. Combined with metabolomics detection, this technology can provide more comprehensive information on the dialogue between gut microbiota and the host. Therefore, this study aims to use multi-omics approaches (metagenomic sequencing and metabolomics detection) to analyze the differences in fecal microbiota and their metabolites between young and elderly populations under different glucose metabolism states. This will provide potential intervention targets for preventing age-related glucose metabolism abnormalities and offer new theoretical foundations for the molecular mechanisms of age-related metabolic diseases.