Gut Microbiota and Antidiabetic Drugs: Perspectives of Personalized Treatment in Type 2 Diabetes Mellitus

Liu, Wenhui; Luo, Zhicheng; Zhou, Jiahao; Sun, Bei

doi:10.3389/fcimb.2022.853771

Cited by 20 publications

(21 citation statements)

References 111 publications

(139 reference statements)

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“…The composition and function of the gut microbiota are altered in patients with type 2 diabetes mellitus (T2DM). 24 Disruption of gut microbiota function and composition may lead to metabolic diseases such as diabetes 25 and obesity. 26 Improving gut microbial metabolism and function can improve host physiology and reduce diabetes and obesity.…”

Section: Discussionmentioning

confidence: 99%

Salidroside Affects Gut Microbiota Structure in db/db Mice by Affecting Insulin, Blood Glucose and Body Weight

Zhao¹,

Shi²,

Chen³

et al. 2022

DMSO

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The purpose of this study was to investigate the regulatory effect of salidroside on the intestinal flora of mice with type 2 diabetes (T2DM) and its protective effect in the body. Patients and Methods:We acclimated 8-week-old mice for 7 days, divided them into 4 groups, and continued dosing for 8 weeks. We recorded weekly blood glucose levels and body weight for each mouse. After the completion of the feeding cycle, the 16S rRNA of the intestinal flora in the mice was sequenced, and the insulin and C-peptide levels in each group of mice were measured. Four samples were taken from each group for liver and kidney section staining. Results: Our results showed that gut microbiota diversity and function were significantly different between the diabetic mice and healthy mice and that insulin levels, body weight, and blood glucose levels could significantly influence gut microbiota changes at the genus level. The gut microbiota diversity and function of db/db mice were also altered after salidroside administration. Salidroside could attenuate inflammatory damage, lipid accumulation and inflammatory changes in the diabetic liver, as well as diabetic kidney damage. Candidatus arthromitus and Odoribacter are important species of the microbiota during diabetes and may serve as potential therapeutic targets. Conclusion: Our investigation of the associated pathological conditions and fecal microbiota in db/db mice provides new insights into the pathogenesis of T2DM and provides implications for the diagnosis and treatment of T2DM.

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Section: Discussionmentioning

confidence: 99%

Salidroside Affects Gut Microbiota Structure in db/db Mice by Affecting Insulin, Blood Glucose and Body Weight

Zhao¹,

Shi²,

Chen³

et al. 2022

DMSO

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show abstract

“…There is a mountain of evidence linking gut microbiota to T2DM and its hypoglycemic therapy. In recent years, a growing body of research now focuses on the bidirectional effects between the gut microbiome and antidiabetic drugs ( 123 , 124 ). In this review, we summarize the microbe-drug-host interactions and provide a novel perspective towards possible personalized treatment for T2DM.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Pharmacomicrobiomics and type 2 diabetes mellitus: A novel perspective towards possible treatment

Huang

Sun²,

Shang

et al. 2023

Front. Endocrinol.

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Type 2 diabetes mellitus (T2DM), a major driver of mortality worldwide, is more likely to develop other cardiometabolic risk factors, ultimately leading to diabetes-related mortality. Although a set of measures including lifestyle intervention and antidiabetic drugs have been proposed to manage T2DM, problems associated with potential side-effects and drug resistance are still unresolved. Pharmacomicrobiomics is an emerging field that investigates the interactions between the gut microbiome and drug response variability or drug toxicity. In recent years, increasing evidence supports that the gut microbiome, as the second genome, can serve as an attractive target for improving drug efficacy and safety by manipulating its composition. In this review, we outline the different composition of gut microbiome in T2DM and highlight how these microbiomes actually play a vital role in its development. Furthermore, we also investigate current state-of-the-art knowledge on pharmacomicrobiomics and microbiome’s role in modulating the response to antidiabetic drugs, as well as provide innovative potential personalized treatments, including approaches for predicting response to treatment and for modulating the microbiome to improve drug efficacy or reduce drug toxicity.

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“…To reduce the prevalence of T2D-related pathophysiologies, nearly 65 medicines have been clinically authorized . Due to the unfortunate reciprocal interplay between gut microbiota and antidiabetic medications, frequent utilization of these medications induces gastrointestinal complications caused by various factors including anaerobic fermentation in the lower gut, ultimately resulting in suboptimal patient adherence. − The HPA, situated at the apex of the starch digestion hierarchy, has the potential to effectively regulate blood glucose levels quantitatively while minimizing the specificity issues that currently exist with α-glucosidase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Raut,

Upadhyaya,

Bashyal

et al. 2023

ACS Omega

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Human pancreatic α-amylase (HPA), situated at the apex of the starch digestion hierarchy, is an attractive therapeutic approach to precisely regulate blood glucose levels, thereby efficiently managing diabetes. Polyphenols offer a natural and multifaceted approach to moderate postprandial sugar spikes, with their slight modulation in carbohydrate digestion and potential secondary benefits, such as antioxidant and antiinflammatory effects. Taking into consideration the unfavorable side effects of currently available commercial medications, we aimed to study a library of polyphenols attributed to their remarkable antidiabetic properties and screened the most potent HPA inhibitor via a comprehensive in silico study encompassing molecular docking, molecular mechanics with generalized Born and surface area solvation (MM/GBSA) calculation, molecular dynamics (MD) simulation, density functional theory (DFT) study, and pharmacokinetic properties followed by an in vitro assay. Significant hydrogen bonding with the catalytic triad residues of HPA, prominent MM/ GBSA binding energy of −27.03 kcal/mol, and the stable nature of the protein−ligand complex with regard to 100 ns MD simulation screened quercetin as the best HPA inhibitor. Additionally, quercetin showed strong reactivity in the substrate-binding pocket of HPA and exhibited favorable pharmacokinetic properties with a considerable inhibitory concentration (IC 50 ) of 57.37 ± 0.9 μg/mL against α-amylase. This study holds prospects for HPA inhibition and suggests quercetin as an approach to therapy for diabetes; however, it is imperative to conduct further research.

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Gut Microbiota and Antidiabetic Drugs: Perspectives of Personalized Treatment in Type 2 Diabetes Mellitus

Cited by 20 publications

References 111 publications

Salidroside Affects Gut Microbiota Structure in db/db Mice by Affecting Insulin, Blood Glucose and Body Weight

Salidroside Affects Gut Microbiota Structure in db/db Mice by Affecting Insulin, Blood Glucose and Body Weight

Pharmacomicrobiomics and type 2 diabetes mellitus: A novel perspective towards possible treatment

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

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