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Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents.

ABSTRACT: Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups; N = 8) and 24 healthy control subjects were enrolled in this study, and intestinal bacterial microbiota was investigated by analyzing V3-V4 regions of 16S rRNA gene sequence. Numerous alterations were observed in the gut microbial community of diabetic individuals. These changes were characterized by a significant lowered abundance of Faecalibacterium, Fusobacterium, Dialister, and Elusimicrobium in the nontherapeutic subgroup compared to the healthy control group. Likewise, correlation analysis showed a substantial decline in gut microbiota richness and diversity with the duration of illness. Furthermore, antidiabetic agents restored to some extent the richness and diversity of gut microbiota and improved the abundance of many beneficial bacteria with a significant increase of Methanobrevibacter in the metformin subcategory compared to the nontherapeutic subgroup. In return, they decreased the abundance of some opportunistic pathogens. The findings of this study have added a novel understanding about the pathogenesis of the disease and the mechanisms underlying antidiabetic therapy, which are of potential interest for therapeutic lines and further studies.

SUBMITTER: Almugadam BS

PROVIDER: S-EPMC7539102 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents.

Almugadam Babiker Saad BS Liu Yinhui Y Chen Shen-Min SM Wang Chun-Hao CH Shao Chen-Yi CY Ren Bao-Wei BW Tang Li L

Journal of diabetes research 20200928

Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups; <i>N</i> = 8) and 24 healthy control subjects we ...[more]

PMID: 33062716

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Project description:BackgroundType 2 diabetes mellitus (T2DM) is a risk factor for acute myocardial infarction (AMI) and a common comorbidity in patients with AMI. T2DM doubles the fatality rate of patients with AMI in the acute phase of AMI and the follow-up period. However, the mechanisms by which T2DM increases the fatality rate remain unknown. This study sought to investigate changes in the gut microbiota of patients with AMI and T2DM (AMIDM) to extend understandings of the relative mechanisms from the aspects of gut microbiota.MethodsPatients were recruited and divided into 2 groups comprising 15 patients with AMIDM and 15 patients with AMI but without T2DM (AMINDM). Their stool samples and clinical information were collected. 16S ribosomal DNA sequencing was used to analyze the structure and composition of the gut microbiota based on the operational taxonomic units.ResultsA significant difference was observed in the gut microbiota β diversity between the 2 groups. At the phylum level, the AMIDM patients showed an increase in the abundance of Firmicutes and a decrease in the abundance of Bacteroidetes compared to the AMINDM patients. At the genus level, the AMIDM patients showed an increase in the abundance of Companilactobacillus, Defluvitaleaceae UCG-011 and UCG-009, and a decrease in the abundance of Phascolarctobacterium and CAG 56 compared to the AMINDM patients. At the species level, the AMIDM patients showed an increase in the abundance of species unclassified NK4A214 group, Bacteroides clarus, Coprococcus comes, unclassified Defluviltaleaceae UCG-011, uncultured rumen bacterium, unclassified CAG 56, Barnesiella intestinihominis, Lachnospiraceae bacterium, Bacteroides nordii, unclassified UCG-009, and the Family XIII AD3011 group compared to the AMINDM patients. The gut microbiota function predictions indicated that the nucleotide metabolism-related pathway was significantly more increase in the patients with AMIDM than those with AMINDM. Additionally, the patients with AMIDM showed an increase in gram-positive bacteria and a decrease in the proportion of gram-negative bacteria. Our correlation analysis results on the gut microbiota and clinical parameters might extend understandings of the progression of AMI.ConclusionsChanges in the gut microbiota composition of patients with AMIDM affect the severity of the metabolic disturbance and may be responsible for poorer clinical outcomes and worse disease progression in patients with AMIDM compared to those with AMINDM.

Project description:BackgroundDiabetes mellitus brings serious threats and financial burdens to human beings worldwide. Fufang Fanshiliu decoction (FFSLD), a traditional Chinese medicine formula showing great antidiabetic effects, has been used in clinics for many years.ObjectiveThis study aims to explore the underlying therapeutic mechanisms of FFSLD in Type II diabetes mellitus (T2DM).MethodsSprague-Dawley rats induced by high-fat diet feeding combined with streptozotocin injection were used to establish the T2DM model. All rats were randomly divided into 6 groups: control, model, metformin, high dosage, middle dosage, and low dosage of FFSLD. After 4 weeks of treatment, serum, intestinal mucosa, and fecal samples were collected for further analysis. ELISA was used to detect the diabetic-related serum indicators and proinflammation cytokines. Gene or protein expressions of mitogen-activated protein kinase (MAPK), interleukin 1 beta (IL-1β), transforming growth factor-beta (TGF-β), and tumor necrosis factor-alpha (TNF-α) in intestinal mucosa were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) or western blot. 16s rRNA gene sequencing was used to detect the changes of gut microbiome in these groups. Intestinal gut microbiota (GM) composition was further analyzed according to the sequencing libraries.ResultsFFSLD effectively recovered the diabetic-related biochemical indexes by reducing fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), insulin, and increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, FFSLD significantly ameliorated the abnormal levels of proinflammation cytokines including IL-1β, IL-6, TNF-α, and TGF-β. In addition, the GM compositions of rats in control, model, and FFSLD treated groups were different. FFSLD significantly increased the relative abundance of Lactobacillus, Akkermansia, and Proteus, and reduced the relative abundance of Alistipes, Desulfovibrio, and Helicobacter. Moreover, these changed bacteria were closely related to the diabetic-related serum indicators and proinflammatory cytokines.ConclusionThese results suggest that FFSLD alleviates diabetic symptoms in T2DM rats through regulating GM composition and inhibiting inflammatory response, which clarify the therapeutic mechanism of FFSLD on T2DM and provide a theoretical basis for its further clinical application.

Dataset Information

Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents.

Publications

Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents.

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