The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus.
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ABSTRACT:
SUBMITTER: Lee CB
PROVIDER: S-EPMC8037857 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Interventions: T2DM:collect feces;normal:collect feces ;colorectal cancer:collect feces;DCRC:collect feces
Primary outcome(s): gut microbiota;blood routine examination;blood biochemistry;Tumor marker;Immune microenvironment
Study Design: Factorial
| 2684404 | ecrin-mdr-crc
Project description:Type 2 diabetes mellitus (T2DM) is a disease that affects over 9% of the United States population and is closely linked to obesity. While obesity was once thought to stem from a sedentary lifestyle and diets high in fat, recent evidence supports the idea that there is more complexity pertinent to the issue. The human gut microbiome has recently been the focus in terms of influencing disease onset. Evidence has shown that the microbiome may be more closely related to T2DM than what was originally thought. High fat diets typically result in poor microbiome heath, which then shifts the gut into a state of dysbiosis. Dysbiosis can then lead to metabolic deregulation, including increased insulin resistance and inflammation, two key factors in the development of T2DM. The purpose of this review is to discuss how microbiome relates to T2DM onset, especially considering obesity, insulin resistance, and inflammation.
| S-EPMC7168169 | biostudies-literature
Project description:PurposeThe purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved.MethodsThirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose < 11.1 mmol/L) groups. Feces were collected and prepared as fecal bacteria supernatants Diab (fecal bacteria supernatant of T2DM group rats), Non (fecal bacteria supernatant of Non-T2DM group rats), and Con (fecal bacteria supernatant of control group rats). Another seventy-nine SPF-grade SD rats were separated into normal saline (NS) and antibiotics (ABX) groups and given normal saline and antibiotics solutions, respectively. In addition, the ABX group rats were randomly separated into ABX-ord (fed with a 4-week ordinary diet), ABX-fat (fed with a 4-week high-fat diet and STZ ip), FMT-Diab (with transplanted fecal bacteria supernatant Diab and fed with a 4-week high-fat diet and STZ ip), FMT-Non (with transplanted fecal bacteria supernatant Non and fed with a 4-week high-fat diet and STZ ip), and FMT-Con (with transplanted fecal bacteria supernatant Con and fed with a 4-week high-fat diet and STZ ip) groups. Furthermore, the NS group was randomly divided into NS-ord (fed with a 4-week ordinary diet) and NS-fat (fed with a 4-week high-fat diet and STZ ip) groups. After this, the short-chain fatty acids (SCFAs) in the feces were detected using gas chromatography, and the gut microbiota were detected using 16S rRNA gene sequencing. Finally, G protein-coupled receptor 41 (GPR41) and GPR43 were detected by western blot and quantitative real-time polymerase chain reaction.ResultsG__Ruminococcus_gnavus_group were more abundant in the FMT-Diab group compared to the ABX-fat and FMT-Non groups. The levels of blood glucose, serum insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also higher in the FMT-Diab group compared to those of the ABX-fat group. Compared to the ABX-fat group, both the FMT-Diab and FMT-Non groups had higher contents of acetic and butyric acid, and the expression of GPR41/43 were significantly higher as well.ConclusionsG__Ruminococcus_gnavus_group might make rats more susceptible to T2DM; T2DM-susceptible flora transplantation increased the susceptibility to T2DM in rats. Additionally, gut microbiota-SCFAs-GPR41/43 may play a role in the development of T2DM. Lowering blood glucose by regulating gut microbiota may therefore become a new strategy for the treatment of T2DM in humans.
| S-EPMC10161507 | biostudies-literature
Project description:The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21-29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM.
| S-EPMC5597849 | biostudies-literature
Project description:UNLABELLED:Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK) activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology. We hypothesized that the pharmacology of metformin includes alteration of bile acid recirculation and gut microbiota resulting in enhanced enteroendocrine hormone secretion. In this study we evaluated T2DM subjects on and off metformin monotherapy to characterize the gut-based mechanisms of metformin. Subjects were studied at 4 time points: (i) at baseline on metformin, (ii) 7 days after stopping metformin, (iii) when fasting blood glucose (FBG) had risen by 25% after stopping metformin, and (iv) when FBG returned to baseline levels after restarting the metformin. At these timepoints we profiled glucose, insulin, gut hormones (glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose-dependent insulinotropic peptide (GIP) and bile acids in blood, as well as duodenal and faecal bile acids and gut microbiota. We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates. These effects reversed when metformin was restarted. Effects on circulating PYY were more modest, while GIP changes were negligible. Microbiota abundance of the phylum Firmicutes was positively correlated with changes in cholic acid and conjugates, while Bacteroidetes abundance was negatively correlated. Firmicutes and Bacteroidetes representation were also correlated with levels of serum PYY. Our study suggests that metformin has complex effects due to gut-based pharmacology which might provide insights into novel therapeutic approaches to treat T2DM and associated metabolic diseases. TRIAL REGISTRATION:www.ClinicalTrials.gov NCT01357876.
| S-EPMC4079657 | biostudies-literature
Project description:BackgroundTo systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM).MethodsFour electronic databases were searched up until December 2018. The manual search included the reference lists of the included studies and relevant journals. Observational studies evaluating the relationship between T2DM and periodontitis were included. Meta-analyses were conducted using STATA.ResultsA total of 53 observational studies were included. The Adjusted T2DM prevalence was significantly higher in periodontitis patients (OR = 4.04, p = 0.000), and vice versa (OR = 1.58, p = 0.000). T2DM patients had significantly worse periodontal status, as reflected in a 0.61 mm deeper periodontal pocket, a 0.89 mm higher attachment loss and approximately 2 more lost teeth (all p = 0.000), than those without T2DM. The results of the cohort studies found that T2DM could elevate the risk of developing periodontitis by 34% (p = 0.002). The glycemic control of T2DM patients might result in different periodontitis outcomes. Severe periodontitis increased the incidence of T2DM by 53% (p = 0.000), and this result was stable. In contrast, the impact of mild periodontitis on T2DM incidence (RR = 1.28, p = 0.007) was less robust.ConclusionsThere is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding. Our results suggest that both dentists and physicians need to be aware of the strong connection between periodontitis and T2DM. Controlling these two diseases might help prevent each other's incidence.
| S-EPMC7353775 | biostudies-literature
Project description:Metformin and liraglutide are used in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD). Although these drugs can alter the intestinal microbiome, clinical data are required to explore their mechanisms of action. Using 16S sequencing technology, we analyzed and compared the intestinal bacterial community structure and function between patients before and after treatment (12 weeks) with the two drugs (metformin or liraglutide, n = 15) and healthy controls (n = 15). Moreover, combined with 19 clinical indices, the potential therapeutic mechanisms of the two drugs were compared. The studied clinical indices included those associated with islet β-cell function (FPG, FINS, HbA1c, and HOMA-IR), inflammation (TNF-α, IL-6, and APN), lipid metabolism (TC, TG, and LDL-C), and liver function (ALT, AST, and GGT); the values of all indices changed significantly after treatment (p < 0.01). In addition, the effect of the two drugs on the intestinal bacterial community varied. Liraglutide treatment significantly increased the diversity and richness of the intestinal bacterial community (p < 0.05); it significantly increased the relative abundances of Bacteroidetes, Proteobacteria, and Bacilli, whereas metformin treatment significantly increased the relative abundance of Fusobacteria and Actinobacteria (p < 0.05). Metformin treatment increased the complexity and stability of the intestinal bacterial network. However, liraglutide treatment had a weaker effect on the intestinal bacterial network, and the network after treatment was similar to that in healthy controls. Correlation matrix analysis between dominant genera and clinical indicators showed that the correlation between the bacterial community and islet β-cell function was stronger after liraglutide treatment, whereas the correlation between the bacterial community and inflammation-related factors was stronger after metformin treatment. Functional prediction showed that liraglutide could significantly affect the abundance of functional genes related to T2DM and NAFLD (p < 0.05), but the effect of metformin was not significant. This study is the first to report the changes in the intestinal bacterial community in patients treated with metformin or liraglutide and the differences between the mechanisms of action of metformin and liraglutide. Metformin or liraglutide has a therapeutic value in T2DM complicated with NAFLD, with liraglutide having a weaker effect on the intestinal bacterial community but a better therapeutic efficacy.
| S-EPMC9909237 | biostudies-literature
Project description:PurposeType 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM.MethodsThis was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA.ResultsThirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups.ConclusionsAlthough alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.
| S-EPMC8118452 | biostudies-literature
Project description:We aimed to explore the effects of type-2 diabetes mellitus (T2DM) and hypoglycemic therapy on the salivary microbiome in periodontitis patients and identify the potential salivary micro-biomarker for the early warning of T2DM. Saliva samples were collected from healthy individuals (Health), periodontitis patients (P), T2DM patients, periodontitis patients with T2DM (DAP), and DAP patients treated with Metformin (Met). Samples were determined by16S rRNA gene sequencing. 29 phyla, 322 genera, and 333 species of salivary microbiome were annotated. Compared to the Health group, the P and DAP group showed a significantly higher diversity of saliva microbiota, while the T2DM and Met group had no significant difference in microbial abundance but showed a trend of increasing diversity. Other than well-known periodontitis-inducing pathogens, the proportion of Prevotella copri, Alloprevotella rava, and Ralstonia pickettii, etc. were also significantly increased in periodontitis patients with or without T2DM. After effective glycemic control, the abundance of Prevotella copri, Alloprevotella rava, Ralstonia pickettii, etc. decreased in periodontitis patients with companion T2DM. The accuracies of the classification models in differentiating Health-vs.-P, DAP-vs.-P, and T2DM-vs.-P were 100%, 96.3%, and 98.1%, respectively. Hypoglycemic therapy could reconstruct the saliva microbiota and hence improve the localized conditions of diabetes patients with periodontitis.
| S-EPMC7506544 | biostudies-literature
Project description:Mounting evidence indicates that gut microbiome may be involved in the pathogenesis of type 2 diabetes mellitus (T2DM). However, there is no consensus on whether there is a causal link between gut microbiome and T2DM risk. In the present study, the Mendelian randomization (MR) analysis was performed to investigate whether gut microbiome was causally linked to T2DM risk. The single nucleotide polymorphisms (SNPs) that were significantly related to exposure from published available genome-wide association study (GWAS) were selected as instrumental variables (IVs). The robust methods including inverse variance weighting (IVW), MR Egger, and weighted median were conducted to infer the causal links. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were used to test whether there was horizontal pleiotropy and identify outlier SNPs. The estimates of IVW suggested that Streptococcaceae (odds ratio (OR) = 1.17, 95% confidence interval (CI), 1.04-1.31, p = 0.009) was associated with higher risk of T2DM in European population. In Asian population, the MR IVW estimates revealed that there was a causal link between Acidaminococcaceae and T2DM risk (OR = 1.17, 95% CI, 1.04-1.31, p = 0.008). There was no evidence of notable heterogeneity and horizontal pleiotropy. However, after false discovery rate (FDR) correction, the causal link between gut microbiome and T2DM was absent (FDR, p > 0.05). In summary, using genetic instruments, this study does not find evidence of association between the 28 gut microbiome families and T2DM risk. However, Streptococcaceae and Acidaminococcaceae may have a borderline positive correlation with T2DM risk.
| S-EPMC8851667 | biostudies-literature