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Outline
To explore the differences in the composition and function of intestinal microbiota among healthy individuals, patients with diabetes, and those with diabetic nephropathy, and to analyze the characteristics of intestinal flora imbalance in patients with advanced diabetic nephropathy, providing references for the mechanism research and prevention and treatment strategy formulation of this disease.
A total of 32 patients with advanced diabetic nephropathy, 79 patients with diabetes mellitus and 55 healthy controls were enrolled from the West China Fourth Hospital and Southwest China natural population cohort. Clinical data were collected and fecal samples were subjected to metagenomic sequencing. Linear discriminant analysis was used to screen for differentially abundant species and functional pathways. Linear regression analysis was performed to investigate the correlation between population phenotypes and differentially abundant species. Random forest and SPIEC-EASI algorithms were used to establish species classifiers and interaction networks, respectively.
There were significant differences in the β-diversity of the intestinal microbiota among the three groups, but no statistically significant differences were observed in the α-diversity. In the advanced stage of diabetic nephropathy patients, the intestines were enriched with various opportunistic pathogenic bacteria (such as Eggerthella lenta, Clostridium innocuum, Hungatella hathewayi, etc.) and harmful pathways such as anaerobic energy metabolism and L-histidine degradation, and were significantly correlated with renal function indicators. The intestines of diabetic patients were characterized by the enrichment of opportunistic pathogenic bacteria (such as Escherichia coli and Klebsiella pneumoniae) and the activation of glycolytic pathways. The random forest model performed best in differentiating the diabetic nephropathy group from the healthy control group (AUC=0.920). The co-abundance network analysis further revealed that the intestinal microbial interaction network of diabetic nephropathy patients was significantly sparser and the topological parameters changed, suggesting that there was an imbalance in the microbial ecological network during the disease process.
From diabetes to the advanced stage of diabetic nephropathy, the intestinal microbiota shows a progressive functional disorder, with an increase in the abundance of harmful bacterial species and metabolic pathways, which is closely related to the progression of the disease.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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