TY - JOUR
T1 - Gut Microbial Signatures for Glycemic Responses of GLP-1 Receptor Agonists in Type 2 Diabetic Patients
T2 - A Pilot Study
AU - Tsai, Chih Yiu
AU - Lu, Hsiu Chen
AU - Chou, Yu Hsien
AU - Liu, Po Yu
AU - Chen, Hsin Yun
AU - Huang, Meng Chuan
AU - Lin, Chia Hung
AU - Tsai, Chi Neu
N1 - Publisher Copyright:
Copyright © 2022 Tsai, Lu, Chou, Liu, Chen, Huang, Lin and Tsai.
PY - 2022/1/10
Y1 - 2022/1/10
N2 - 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 (n = 34) and non-responders (n = 18) (ADONIS, P = 0.004). The top 17 features associated with glycohemoglobin reduction had a 0.96 diagnostic ability, based on area under the ROC curve: Bacteroides dorei and Roseburia inulinivorans, the two microbes having immunomodulation effects, along with Lachnoclostridium sp. and Butyricicoccus sp., were positively correlated with glycemic reduction; Prevotella copri, the microbe related to insulin resistance, together with Ruminococcaceae sp., Bacteroidales sp., Eubacterium coprostanoligenes sp., Dialister succinatiphilus, Alistipes obesi, Mitsuokella spp., Butyricimonas virosa, Moryella sp., and Lactobacillus mucosae had negative correlation. Furthermore, Bacteroides dorei, Lachnoclostridium sp. and Mitsuokella multacida 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.
AB - 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 (n = 34) and non-responders (n = 18) (ADONIS, P = 0.004). The top 17 features associated with glycohemoglobin reduction had a 0.96 diagnostic ability, based on area under the ROC curve: Bacteroides dorei and Roseburia inulinivorans, the two microbes having immunomodulation effects, along with Lachnoclostridium sp. and Butyricicoccus sp., were positively correlated with glycemic reduction; Prevotella copri, the microbe related to insulin resistance, together with Ruminococcaceae sp., Bacteroidales sp., Eubacterium coprostanoligenes sp., Dialister succinatiphilus, Alistipes obesi, Mitsuokella spp., Butyricimonas virosa, Moryella sp., and Lactobacillus mucosae had negative correlation. Furthermore, Bacteroides dorei, Lachnoclostridium sp. and Mitsuokella multacida 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.
KW - GLP-1 receptor agonists
KW - GLP-1 resistance
KW - dysbiosis
KW - glycemic response
KW - gut microbiota
KW - type 2 diabetes mellitus
UR - https://www.scopus.com/pages/publications/85123762286
U2 - 10.3389/fendo.2021.814770
DO - 10.3389/fendo.2021.814770
M3 - 文章
AN - SCOPUS:85123762286
SN - 1664-2392
VL - 12
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 814770
ER -
