Abstract
Background: The relationship between gut microbiota and metabolites play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). However, the interaction between intestinal flora abundance and metabolites is still unclear. The purpose of this study was to investigate the correlation of the interaction network between intestinal flora and fecal metabolites in regulating the occurrence of T2DM. Methods: This a case-control study. T2DM patients with different glucose levels and healthy people were divided into case group and normal controls (NC) group. Fasting plasma and fecal samples were collected from the subjects. Ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS) untargeted fecal metabolomics was used to detect small molecular metabolites within 1,500 Da in two groups. The diversity and richness of intestinal flora were analyzed by the 16SrRNA third-generation full-length sequencing technique and the correlation between intestinal microflora and different metabolites was evaluated. Results: A total of 30 patients with T2DM and 21 NC were included for analysis, glycated hemoglobin (HbAlc) (P<0.001), fasting blood glucose (FBG) (P<0.001), total triglycerides (TG) (P=0.002), and fasting serum insulin (FINS) (P=0.026) were significantly higher in the T2DM group compared with the NC group. The fecal metabolomics profiles of the T2DM group and NC group were significantly different, and 355 different metabolites were identified among the two. Compared with the NC group, the levels of ornithine (P=0.04), L-lysine (P=0.03), glutamate (P=0.01), alpha-linolenic acid (P=0.004), traumatin (P=0.05), and erucic acid (P=0.004) in the T2DM group decreased significantly, while PC[18:3(6Z,9Z,12Z)/24:1(15Z)] (P<0.001) levels increased. Compared with the NC group, the richness of Megamonas and Escherichia increased in T2DM patients, while that of Bacteroidota and Phascolarctobacterium were lower. Pearson correlation analysis revealed associations between gut microbiota and faecal metabolites, and Phascolarctobacterium was positively correlated with alpha-linolenic acid (r=0.72, P<0.001). Conclusions: There may be a mutual regulatory network between intestinal bacteria and fecal metabolites in T2DM. The increased abundance of Phascolarctobacterium may increase alpha-linolenic acid uptake, and alpha-linolenic acid may also increase the abundance of intestinal Phascolarctobacterium in vivo after metabolic transformation. The combination of the two may play an important role in the treatment of diabetes.
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