Gut Microbial Signatures for Glycemic Responses of GLP-1 Receptor Agonists in Type 2 Diabetic Patients: A Pilot Study.

Backgrounds: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) is probably one of more effective antidiabetic agents in treatment of type 2 diabetes mellitus (T2D). However, the heterogenicity in responses to GLP-1 RA may be potentially related to gut microbiota, although no human evidence has been published. This pilot study aims to identify microbial signatures associated with glycemic responses to GLP-1 RA.

Materials And Methods: Microbial compositions of 52 patients with T2D receiving GLP-1 RA were determined by 16S rRNA amplicon sequencing. Bacterial biodiversity was compared between responders versus non-responders. Pearson's correlation and random forest tree algorithm were used to identify microbial features of glycemic responses in T2D patients and multivariable linear regression models were used to validate clinical relevance.

Results: Beta diversity significantly differed between GLP-1 RA responders ( = 34) and non-responders ( = 18) (ADONIS, = 0.004). The top 17 features associated with glycohemoglobin reduction had a 0.96 diagnostic ability, based on area under the ROC curve: and , the two microbes having immunomodulation effects, along with sp. and sp., were positively correlated with glycemic reduction; , the microbe related to insulin resistance, together with sp., Bacteroidales sp., sp., , , spp., , sp., and had negative correlation. Furthermore, , sp. and were significant after adjusting for baseline glycohemoglobin and C-peptide concentrations, two clinical confounders.

Conclusions: Unique gut microbial signatures are associated with glycemic responses to GLP-RA treatment and reflect degrees of dysbiosis in T2D patients.