Crosstalk between gut microbiota and antidiabetic drug action

Abstract

Type 2 diabetes (T2D) is a disorder characterized by chronic inflated blood glucose levels (hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin, α-glucosidase inhibitors, glucagon-like peptide-1 agonists, peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2D, and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria, responsible for losing weight and suppressing inflammation.

Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats

“…It was validated by previous studies that acarbose18 and metformin7 promoted the level of Lactobacillus genus. Wang et al showed that the genera Lactobacillus , Allobaculum and Turicibacter were also enriched following liraglutide and saxagliptin dosage 29 30. There was little research on the taxonomic composition of sitagliptin.…”

Metformin as an archetype immuno-metabolic adjuvant for cancer immunotherapy

“…[74][75][76][77][78][79][80] Metformin treatment of mice on high-fat diet or of patients with diabetes has been shown to shift the microbiota composition to an increased relative abundance of A. muciniphila, a mucolytic bacterium. [77][78][79] Because cancer patients with augmented memory T-cells targeting the gut colonization of A. muciniphila are prone to have a longer clinical benefit from PD-1-based immunotherapy, metformin's ability to strengthen the intestinal mucosal barrier via enrichment of A. muciniphila and associated improvement in mucinproducing goblet cells might promote a salutatory bacteriaspecific synergetic immune response in combination with immune checkpoint inhibitors. Also, modulation of the gut 59 IFNγ-treated haploid HAP1 cells express high levels of cell surface PD-L1.…”

Corrigendum: The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2 (Diabetes mellitus. 2019;22(3). doi: 10.14341/DM10194)

“…По результатам нескольких исследований сделано предположение, что некоторые препараты из группы сульфонилмочевины могут оказывать некоторое благотворное влияние на кишечную микробиоту у пациентов с СД2, благодаря способности метаболизировать растительные фенольные и ароматические аминокислоты (гиппурат, фенилаланин и триптофан). Однако нельзя сделать однозначных выводов, так как до настоящего времени ни в одном исследовании не изучалось прямое влияние сульфонилмочевины на микробиоту кишечника [52,59].…”