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

Abstract

BackgroundsGlucagon-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 MethodsMicrobial 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.ResultsBeta 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.ConclusionsUnique gut microbial signatures are associated with glycemic responses to GLP-RA treatment and reflect degrees of dysbiosis in T2D patients.

Interplay of Lymphocytes with the Intestinal Microbiota in Children with Nonalcoholic Fatty Liver Disease

“…Rothia were enriched in the FLD_HL_M group. Prevotella copri reduces lymphocyte infiltration and prevents inflammatory responses by activating Toll-like receptor 2 [ 46 ]. Bifidobacterium catenulatum is anti-inflammatory and contributes to other probiotics that produce butyrate [ 47 ].…”

GLP-1 and GLP-2 Orchestrate Intestine Integrity, Gut Microbiota, and Immune System Crosstalk

“…abundance in patients with obesity after gastric bypass surgery and dietary intervention [ 200 , 201 ]. A recent study found a significant difference in the Beta diversity of the gut microbiota between GLP-1 R agonist responder and non-responder patients with T2D [ 202 ]. Decreased levels of HbA1c in the responder group correlated with increase abundance of Bacteroides dorei , Lachnoclostridium sp., Mitsuokella multacida , and Prevotella copri 202 .…”

“…The representative positive signatures for GLP-1R agonist hyperglycemia responses were Bacteroides dorei and Lachnoclostridium sp., whereas the representative negative signature was Mitsuokella multacida . They also observed that Bacteroides dorei and Roseburia inulinivorans were more abundant, indicating that GLP-1R agonist responders have reduced inflammation because of their role in enhancing gut barrier function and production of butyrate-derived metabolites [ 202 ]. Over last few years, scientific breakthroughs have expanded our understanding on an interesting communication circuit where microbiota, intestine, liver, and brain are interconnected to regulate metabolism and energy expenditure [ 203 , 204 , 205 , 206 ].…”

The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus

“…A significant difference in the composition of the gut microbiota was observed between respondents and non-responders to GLP-1RA treatment. Thus, in the GLP-1RAs respondent group, the decrease in blood glucose level was positively correlated with Bacteroides dorei , Roseburia inulinivorans , Lachnoclostridium sp., and Butyricicoccus , while it was negatively correlated with Prevotella copri , Ruminococcaceae sp., Bacteroidales sp., Dialister succinatiphilus , and Alistipes obese [ 93 ].…”