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

Objective Recent studies have demonstrated that gut microbiota was closely related to metabolic disorders such as type 2 diabetes. Oral antidiabetic medications including metformin, acarbose and sitagliptin lowered blood glucose levels via acting on the gastrointestinal tract. The aim of the study w...

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Main Authors: Wei Liu, Jing Ma, Rilu Feng, Mei Yang, Minchun Zhang, Cheng Qian
Format: Article
Language:English
Published: BMJ Publishing Group 2019-05-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/7/1/e000717.full
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author Wei Liu
Jing Ma
Rilu Feng
Mei Yang
Minchun Zhang
Cheng Qian
author_facet Wei Liu
Jing Ma
Rilu Feng
Mei Yang
Minchun Zhang
Cheng Qian
author_sort Wei Liu
collection DOAJ
description Objective Recent studies have demonstrated that gut microbiota was closely related to metabolic disorders such as type 2 diabetes. Oral antidiabetic medications including metformin, acarbose and sitagliptin lowered blood glucose levels via acting on the gastrointestinal tract. The aim of the study was to observe the comparisons among those medications on gut microbiota composition.Research design and methods Zucker diabetic fatty rats (n=32) were randomly divided into four groups, and had respectively gastric administration of normal saline (control), metformin (215.15 mg/kg/day), acarbose (32.27 mg/kg/day), or sitagliptin (10.76 mg/kg/day) for 4 weeks. Blood glucose levels were measured during an intragastric starch tolerance test after the treatments. 16S rRNA gene sequencing was used to access the microbiota in the fecal samples.Results Metformin, acarbose, and sitagliptin monotherapy effectively decreased fasting and postprandial blood glucose levels (p<0.001). Acarbose group displayed specific cluster and enterotype mainly composed by Ruminococcus 2 while Lactobacillus was the dominant bacterium in the enterotype of the other three groups. The relative abundance of genera Ruminococcus 2 and Bifidobacterium was dramatically higher in acarbose group. Metformin and sitagliptin increased the relative abundance of genus Lactobacillus. Metagenomic prediction showed that the functional profiles of carbohydrate metabolism were enriched in acarbose group.Conclusions Metformin, acarbose and sitagliptin exerted different effects on the composition of gut microbiota and selectively increased the beneficial bacteria. Supplementation with specific probiotics may further improve the hypoglycemic effects of the antidiabetic drugs.
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spelling doaj-art-cf60ffcd510544738dcb0b3ee8863bad2024-12-15T16:20:09ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972019-05-017110.1136/bmjdrc-2019-000717Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty ratsWei Liu0Jing Ma1Rilu Feng2Mei Yang3Minchun Zhang4Cheng Qian5Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA1 Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, GermanyDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaObjective Recent studies have demonstrated that gut microbiota was closely related to metabolic disorders such as type 2 diabetes. Oral antidiabetic medications including metformin, acarbose and sitagliptin lowered blood glucose levels via acting on the gastrointestinal tract. The aim of the study was to observe the comparisons among those medications on gut microbiota composition.Research design and methods Zucker diabetic fatty rats (n=32) were randomly divided into four groups, and had respectively gastric administration of normal saline (control), metformin (215.15 mg/kg/day), acarbose (32.27 mg/kg/day), or sitagliptin (10.76 mg/kg/day) for 4 weeks. Blood glucose levels were measured during an intragastric starch tolerance test after the treatments. 16S rRNA gene sequencing was used to access the microbiota in the fecal samples.Results Metformin, acarbose, and sitagliptin monotherapy effectively decreased fasting and postprandial blood glucose levels (p<0.001). Acarbose group displayed specific cluster and enterotype mainly composed by Ruminococcus 2 while Lactobacillus was the dominant bacterium in the enterotype of the other three groups. The relative abundance of genera Ruminococcus 2 and Bifidobacterium was dramatically higher in acarbose group. Metformin and sitagliptin increased the relative abundance of genus Lactobacillus. Metagenomic prediction showed that the functional profiles of carbohydrate metabolism were enriched in acarbose group.Conclusions Metformin, acarbose and sitagliptin exerted different effects on the composition of gut microbiota and selectively increased the beneficial bacteria. Supplementation with specific probiotics may further improve the hypoglycemic effects of the antidiabetic drugs.https://drc.bmj.com/content/7/1/e000717.full
spellingShingle Wei Liu
Jing Ma
Rilu Feng
Mei Yang
Minchun Zhang
Cheng Qian
Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
BMJ Open Diabetes Research & Care
title Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
title_full Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
title_fullStr Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
title_full_unstemmed Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
title_short Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
title_sort effects of metformin acarbose and sitagliptin monotherapy on gut microbiota in zucker diabetic fatty rats
url https://drc.bmj.com/content/7/1/e000717.full
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