Skip to main content

18.05.2024 | Original Article

Metformin-induced changes of the gut microbiota in patients with type 2 diabetes mellitus: results from a prospective cohort study

verfasst von: Yuting Gao, Tianyi Zhao, Na Lv, Shixuan Liu, Tao Yuan, Yong Fu, Weigang Zhao, Baoli Zhu

Erschienen in: Endocrine

Einloggen, um Zugang zu erhalten

Abstract

Background

The influence of the microbiota on hypoglycemic agents is becoming more apparent. The effects of metformin, a primary anti-diabetes drug, on gut microbiota are still not fully understood.

Research design and methods

This prospective cohort study aims to investigate the longitudinal effects of metformin on the gut microbiota of 25 treatment-naïve diabetes patients, each receiving a daily dose of 1500 mg. Microbiota compositions were analyzed at baseline, and at 1, 3, and 6 months of medication using 16S rRNA gene sequencing.

Results

Prior to the 3-month period of metformin treatment, significant improvements were noted in body mass index (BMI) and glycemic-related parameters, such as fasting blood glucose (FPG) and hemoglobin A1c (HbA1c), alongside homeostasis model assessment indices of insulin resistance (HOMA-IR). At the 3-month mark of medication, a significant reduction in the α-diversity of the gut microbiota was noted, while β-diversity exhibited no marked variances throughout the treatment duration. The Firmicutes to Bacteroidetes ratio. markedly decreased. Metformin treatment consistently increased Escherichia-Shigella and decreased Romboutsia, while Pseudomonas decreased at 3 months. Fuzzy c-means clustering identified three longitudinal trajectory clusters for microbial fluctuations: (i) genera temporarily changing, (ii) genera continuing to decrease (Bacteroides), and (iii) genera continuing to increase(Lachnospiraceae ND3007 group, [Eubacterium] xylanophilum group, Romboutsia, Faecalibacterium and Ruminococcaceae UCG-014). The correlation matrix revealed associations between specific fecal taxa and metformin-related clinical parameters HbA1c, FPG, Uric Acid (UA), high-density lipoproteincholesterol (HDL-C), alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), triglyceride (TG) (P < 0.05). Metacyc database showed that metformin significantly altered 17 functional pathways. Amino acid metabolism pathways such as isoleucine biosynthesis predominated in the post-treatment group.

Conclusions

Metformin’s role in glucose metabolism regulation may primarily involve specific alterations in certain gut microbial species rather than an overall increase in microbial species diversity. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by metformin.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
6.
Zurück zum Zitat R. Li, F. Shokri, A.L. Rincon, F. Rivadeneira, C. Medina-Gomez, F. Ahmadizar, Bi-Directional Interactions between Glucose-Lowering Medications and Gut Microbiome in Patients with Type 2 Diabetes Mellitus: A Systematic Review. Genes. 14(8) (2023) https://doi.org/10.3390/genes14081572 R. Li, F. Shokri, A.L. Rincon, F. Rivadeneira, C. Medina-Gomez, F. Ahmadizar, Bi-Directional Interactions between Glucose-Lowering Medications and Gut Microbiome in Patients with Type 2 Diabetes Mellitus: A Systematic Review. Genes. 14(8) (2023) https://​doi.​org/​10.​3390/​genes14081572
11.
Zurück zum Zitat J.B. Buse, R.A. DeFronzo, J. Rosenstock, T. Kim, C. Burns, S. Skare et al. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies. Diabetes Care 39(2), 198–205 (2016). https://doi.org/10.2337/dc15-0488CrossRefPubMed J.B. Buse, R.A. DeFronzo, J. Rosenstock, T. Kim, C. Burns, S. Skare et al. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies. Diabetes Care 39(2), 198–205 (2016). https://​doi.​org/​10.​2337/​dc15-0488CrossRefPubMed
15.
Zurück zum Zitat J. de la Cuesta-Zuluaga, N.T. Mueller, V. Corrales-Agudelo, E.P. Velasquez-Mejia, J.A. Carmona, J.M. Abad et al. Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut. Diabetes Care 40(1), 54–62 (2017). https://doi.org/10.2337/dc16-1324CrossRefPubMed J. de la Cuesta-Zuluaga, N.T. Mueller, V. Corrales-Agudelo, E.P. Velasquez-Mejia, J.A. Carmona, J.M. Abad et al. Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut. Diabetes Care 40(1), 54–62 (2017). https://​doi.​org/​10.​2337/​dc16-1324CrossRefPubMed
36.
Zurück zum Zitat H.S. Ejtahed, R.Y. Tito, S.D. Siadat, S. Hasani-Ranjbar, Z. Hoseini-Tavassol, L. Rymenans et al. Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial. Eur. J. Endocrinol. 180(3), 165–176 (2019). https://doi.org/10.1530/EJE-18-0826CrossRefPubMed H.S. Ejtahed, R.Y. Tito, S.D. Siadat, S. Hasani-Ranjbar, Z. Hoseini-Tavassol, L. Rymenans et al. Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial. Eur. J. Endocrinol. 180(3), 165–176 (2019). https://​doi.​org/​10.​1530/​EJE-18-0826CrossRefPubMed
40.
Zurück zum Zitat T. Tavella, S. Rampelli, G. Guidarelli, A. Bazzocchi, C. Gasperini, E. Pujos-Guillot et al. Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly. Gut Microbes 13(1), 1–19 (2021). https://doi.org/10.1080/19490976.2021.1880221CrossRefPubMed T. Tavella, S. Rampelli, G. Guidarelli, A. Bazzocchi, C. Gasperini, E. Pujos-Guillot et al. Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly. Gut Microbes 13(1), 1–19 (2021). https://​doi.​org/​10.​1080/​19490976.​2021.​1880221CrossRefPubMed
50.
Zurück zum Zitat H. Wu, E. Esteve, V. Tremaroli, M.T. Khan, R. Caesar, L. Manneras-Holm et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23(7), 850–858 (2017). https://doi.org/10.1038/nm.4345CrossRefPubMed H. Wu, E. Esteve, V. Tremaroli, M.T. Khan, R. Caesar, L. Manneras-Holm et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23(7), 850–858 (2017). https://​doi.​org/​10.​1038/​nm.​4345CrossRefPubMed
52.
Zurück zum Zitat M. Million, E. Angelakis, M. Maraninchi, M. Henry, R. Giorgi, R. Valero et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int. J. Obes. 37(11), 1460–1466 (2013). https://doi.org/10.1038/ijo.2013.20CrossRef M. Million, E. Angelakis, M. Maraninchi, M. Henry, R. Giorgi, R. Valero et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int. J. Obes. 37(11), 1460–1466 (2013). https://​doi.​org/​10.​1038/​ijo.​2013.​20CrossRef
Metadaten
Titel
Metformin-induced changes of the gut microbiota in patients with type 2 diabetes mellitus: results from a prospective cohort study
verfasst von
Yuting Gao
Tianyi Zhao
Na Lv
Shixuan Liu
Tao Yuan
Yong Fu
Weigang Zhao
Baoli Zhu
Publikationsdatum
18.05.2024
Verlag
Springer US
Erschienen in
Endocrine
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-024-03828-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.