Abstract
BACKGROUND: Emerging evidence demonstrates correlations among the gut microbiota, fecal short-chain fatty acids (SCFAs) and glucose metabolism. Few studies focus on post-gestational diabetes women. This study aimed to compare the gut microbiota and fecal SCFAs among different states of postpartum glucose metabolism in women with previous gestational diabetes mellitus (p-GDM). METHODS: The study finally recruited 60 women with p-GDM including 16 healthy controls (HC), 40 Pre-diabetes (Pre-DM) patients and 4 type 2 diabetes patients according to a 2-h 75-g oral glucose tolerance. Stool samples were obtained 1-5 years after delivery. Gut microbiota was obtained by sequencing V3-V4 region of 16S rRNA gene and fecal SCFAs were measured by gas chromatography-mass spectrometry. The microbial community structure of the Pre-DM group, as revealed by principal coordinates analysis (PCoA), exhibited distinct clustering that was further validated by hierarchical clustering, definitively identifying two subgroups: Pre-DM1 and Pre-DM2. The primary analyses in this report compared the HC and Pre-DM groups, with a particular focus on a three-group comparison (HC vs. Pre-DM1 vs. Pre-DM2) to demonstrate heterogeneity within Pre-DM. For the type 2 diabetes group, only descriptive statistics were presented, without formal statistical testing. RESULTS: No significant differences were observed in age, BMI and months post-delivery between HC and Pre-DM group. The Pre-DM group exhibited two distinct clustering patterns: Pre-DM1 (n = 25) and Pre-DM2 (n = 15). The gut microbiota structure of Pre-DM1 largely overlapped with the HC group, while Pre-DM2 was closer to the type 2 diabetes group. Compared to the HC group, the relative abundance of Faecalibacterium, Ruminococcus, and Subdoligranulum remained unchanged in Pre-DM1 group, while significantly reduced in Pre-DM2 group. Furthermore, compared with HC group, acetic acid and propionic acid were increased in the Pre-DM1 group while were similar to Pre-DM2. HC group had higher concentration of caproic acid than Pre-DM1 (P = 0.01) and Pre-DM2 (P = 0.02). CONCLUSIONS: Our study discovered that dysbiosis of the gut microbial structure and alterations in SCFAs had already been present in women with Pre-DM and further revealed two subsets of Pre-DM with remarkable heterogeneity. Further studies are needed to explore whether the heterogeneity can help predict postpartum glycemic states.