AUTHOR=Tsai Chih-Yiu , Lu Hsiu-Chen , Chou Yu-Hsien , Liu Po-Yu , Chen Hsin-Yun , Huang Meng-Chuan , Lin Chia-Hung , Tsai Chi-Neu 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.814770

DOI=10.3389/fendo.2021.814770

ISSN=1664-2392

ABSTRACT=<sec><title>Backgrounds</title><p>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.</p></sec><sec><title>Materials and Methods</title><p>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.</p></sec><sec><title>Results</title><p>Beta diversity significantly differed between GLP-1 RA responders (<italic>n</italic> = 34) and non-responders (<italic>n</italic> = 18) (ADONIS, <italic>P</italic> = 0.004). The top 17 features associated with glycohemoglobin reduction had a 0.96 diagnostic ability, based on area under the ROC curve: <italic>Bacteroides dorei</italic> and <italic>Roseburia inulinivorans</italic>, the two microbes having immunomodulation effects, along with <italic>Lachnoclostridium</italic> sp. and <italic>Butyricicoccus</italic> sp., were positively correlated with glycemic reduction; <italic>Prevotella copri</italic>, the microbe related to insulin resistance, together with <italic>Ruminococcaceae</italic> sp., Bacteroidales sp., <italic>Eubacterium coprostanoligenes</italic> sp., <italic>Dialister succinatiphilus</italic>, <italic>Alistipes obesi</italic>, <italic>Mitsuokella</italic> spp., <italic>Butyricimonas virosa</italic>, <italic>Moryella</italic> sp., and <italic>Lactobacillus mucosae</italic> had negative correlation. Furthermore, <italic>Bacteroides dorei</italic>, <italic>Lachnoclostridium</italic> sp. and <italic>Mitsuokella multacida</italic> were significant after adjusting for baseline glycohemoglobin and C-peptide concentrations, two clinical confounders.</p></sec><sec><title>Conclusions</title><p>Unique gut microbial signatures are associated with glycemic responses to GLP-RA treatment and reflect degrees of dysbiosis in T2D patients.</p></sec>