The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. Gut microbiota has been implicated to play a critical role in metabolic diseases and may modulate the secretion of mediators of the brain–gut axis. Interaction between gut microbiota and the endocrine and biochemical disturbances in PCOS still remains elusive. Here, we showed an altered gut microbiota significantly correlated with PCOS phenotype. There were 33 patients with PCOS (non-obese PCOS individuals, PN, n = 12; obese PCOS individuals, PO, n = 21) as well as 15 control subjects (non-obese control individuals, CN, n = 9; obese control individuals, CO, n = 6) enrolled in our study. The plasma levels of serotonin, ghrelin, and peptide YY (PYY) were significantly decreased in patients with PCOS compared with controls, and have a significantly negative correlation with waist circumference and testosterone. Sequencing of the V3–V4 region of the 16S rRNA gene in fecal samples revealed the substantial differences of gut microbial species between the PCOS and non-obese controls. Bacterial species were clustered into 23 co-abundance groups (CAGs) based on the SparCC correlation coefficients of their relative abundance. The CAGs increased in PCOS, including the bacteria belonging to Bacteroides, Escherichia/Shigella and Streptococcus, were negatively correlated with ghrelin, and positively correlated with testosterone and BMI. Furthermore, the CAGs that were decreased in PCOS, including the bacteria from Akkermansia and Ruminococcaceae, showed opposite relationship with body-weight, sex-hormone, and brain–gut peptides. In conclusion, gut microbial dysbiosis in women with PCOS is associated with the disease phenotypes.