Skip to main content
Erschienen in:

01.06.2019 | Review Article

Metformin and gut microbiota: their interactions and their impact on diabetes

verfasst von: Natalia G. Vallianou, Theodora Stratigou, Stylianos Tsagarakis

Erschienen in: Hormones | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

The ratio of human to bacterial cells in the human body (microbiota) is around 1:1. As a result of co-evolution of the host mucosal immune system and the microbiota, both have developed multiple mechanisms to maintain homeostasis. However, dissociations between the composition of the gut microbiota and the human host may play a crucial role in the development of type 2 diabetes. Metformin, the most frequently administered medication to treat patients with type 2 diabetes, has only recently been suggested to alter gut microbiota composition through the increase in mucin-degrading Akkermansia muciniphila, as well as several SCFA-producing (short-chain fatty acid) microbiota. The gut microbiota of participants on metformin has exerted alterations in gut metabolomics with increased ability to produce butyrate and propionate, substances involved in glucose homeostasis. Thus, metformin appears to affect the microbiome, and an individual’s metformin tolerance or intolerance may be influenced by their microbiome. In this review, we will focus on the effects of metformin in gut microbiota among patients with T2DM.
Literatur
1.
4.
Zurück zum Zitat Qin J, Li Y, Cai Z et al (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60CrossRefPubMed Qin J, Li Y, Cai Z et al (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60CrossRefPubMed
5.
Zurück zum Zitat Karlsson FH, Tremaroli V, Nookaew I et al (2013) Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498:99–103CrossRefPubMed Karlsson FH, Tremaroli V, Nookaew I et al (2013) Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498:99–103CrossRefPubMed
6.
Zurück zum Zitat Larsen N, Vogensen FK, van den Berg FWJ et al (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5:e9085CrossRefPubMedPubMedCentral Larsen N, Vogensen FK, van den Berg FWJ et al (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5:e9085CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Tilg H, Moschen AR (2014) Microbiota and diabetes: an evolving relationship. Gut 63:1513–1521CrossRefPubMed Tilg H, Moschen AR (2014) Microbiota and diabetes: an evolving relationship. Gut 63:1513–1521CrossRefPubMed
9.
Zurück zum Zitat Forslund K, Hildebrand F, Nielsen T et al (2015) Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–266CrossRefPubMedPubMedCentral Forslund K, Hildebrand F, Nielsen T et al (2015) Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–266CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat de la Cuesta-Zuluaga J, Mueller NT, Vanessa Corrales-Agudelo V et al (2017) 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 40:54–62CrossRefPubMed de la Cuesta-Zuluaga J, Mueller NT, Vanessa Corrales-Agudelo V et al (2017) 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 40:54–62CrossRefPubMed
11.
Zurück zum Zitat Bennett D (2005) Growing pains for metabolomics. Scientist 19(8):25–28 Bennett D (2005) Growing pains for metabolomics. Scientist 19(8):25–28
12.
Zurück zum Zitat Pedersen HK, Gudmundsdottir V, Nielsen HB et al (2016) Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535:376–381CrossRefPubMed Pedersen HK, Gudmundsdottir V, Nielsen HB et al (2016) Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535:376–381CrossRefPubMed
13.
15.
Zurück zum Zitat Shin NR, Lee JC, Lee HY et al (2014) An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63:727–735CrossRefPubMed Shin NR, Lee JC, Lee HY et al (2014) An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63:727–735CrossRefPubMed
16.
Zurück zum Zitat Napolitano A, Miller S, Nicholls AW et al (2014) Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoS One 9:e100778CrossRefPubMedPubMedCentral Napolitano A, Miller S, Nicholls AW et al (2014) Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoS One 9:e100778CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Gall WE, Beebe K, Lawton KA et al (2010) α-Hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One 5:e10883CrossRefPubMedPubMedCentral Gall WE, Beebe K, Lawton KA et al (2010) α-Hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One 5:e10883CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Bonora E, Cigolini M, Bosello O et al (1984) Lack of effect of intravenous metformin on plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in non-diabetic subjects. Curr Med Res Opin 9:47–51CrossRefPubMed Bonora E, Cigolini M, Bosello O et al (1984) Lack of effect of intravenous metformin on plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in non-diabetic subjects. Curr Med Res Opin 9:47–51CrossRefPubMed
19.
Zurück zum Zitat Bailey CJ, Wilcock C, Scarpello JH (2008) Metformin and the intestine. Diabetologia 51:1552–1553CrossRefPubMed Bailey CJ, Wilcock C, Scarpello JH (2008) Metformin and the intestine. Diabetologia 51:1552–1553CrossRefPubMed
20.
Zurück zum Zitat Sekar S, Chandrasekaran A, Rao U, Sastry TP (2011) Comparison of some of the physicochemical characteristics of type 2 diabetic and normal human bones: a sample study. J Diabetes Complicat 25:187–192CrossRef Sekar S, Chandrasekaran A, Rao U, Sastry TP (2011) Comparison of some of the physicochemical characteristics of type 2 diabetic and normal human bones: a sample study. J Diabetes Complicat 25:187–192CrossRef
21.
Zurück zum Zitat DeFronzo RA, Buse JB, Kim T et al (2016) Once-daily delayed release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia 59:1645–1654CrossRefPubMedPubMedCentral DeFronzo RA, Buse JB, Kim T et al (2016) Once-daily delayed release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia 59:1645–1654CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Buse JB, DeFronzo RA, Rosenstock J et al (2016) 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 39:198–205CrossRefPubMed Buse JB, DeFronzo RA, Rosenstock J et al (2016) 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 39:198–205CrossRefPubMed
23.
24.
Zurück zum Zitat Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE (2012) Metformin pathways: pharmacokinetic and pharmacodynamics. Pharmacogenet Genomics 22(11):820–827CrossRefPubMedPubMedCentral Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE (2012) Metformin pathways: pharmacokinetic and pharmacodynamics. Pharmacogenet Genomics 22(11):820–827CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM (2002) Interactions of N-tetraalkylammonium compounds and biguanides with a human renal organic cation tranporter (hOCT2). Pharm Res 19:1244–1247CrossRefPubMed Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM (2002) Interactions of N-tetraalkylammonium compounds and biguanides with a human renal organic cation tranporter (hOCT2). Pharm Res 19:1244–1247CrossRefPubMed
26.
Zurück zum Zitat Kimura N, Masuda S, Tanihara Y et al (2005) Metformin is a superior substrate for renal organic cation tranporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet 20:379–386CrossRefPubMed Kimura N, Masuda S, Tanihara Y et al (2005) Metformin is a superior substrate for renal organic cation tranporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet 20:379–386CrossRefPubMed
27.
Zurück zum Zitat Urakami Y, Nakamura N, Takahashi K et al (1999) Gender differences in expression of organic cation transporter OCT2 in rat kidney. FEBS Lett 461:339–342CrossRefPubMed Urakami Y, Nakamura N, Takahashi K et al (1999) Gender differences in expression of organic cation transporter OCT2 in rat kidney. FEBS Lett 461:339–342CrossRefPubMed
28.
Zurück zum Zitat Urakami Y, Okuda M, Saito H, Inui K (2000) Hormonal regulation of organic cation transporter OCT2 expression in rat kidney. FEBS Lett 473:173–176CrossRefPubMed Urakami Y, Okuda M, Saito H, Inui K (2000) Hormonal regulation of organic cation transporter OCT2 expression in rat kidney. FEBS Lett 473:173–176CrossRefPubMed
29.
Zurück zum Zitat Asaka J, Terada T, Okuda M, Katsura T, Inui K (2006) Androgen receptor is responsible for rat organic cation transporter 2 gene regulation but not for rOCT1 and rOCT3. Pharm Res 23:697–704CrossRefPubMed Asaka J, Terada T, Okuda M, Katsura T, Inui K (2006) Androgen receptor is responsible for rat organic cation transporter 2 gene regulation but not for rOCT1 and rOCT3. Pharm Res 23:697–704CrossRefPubMed
30.
Zurück zum Zitat Leabman MK, Giacomini KM (2003) Estimating the contribution of genes and environment to variation in renal drug clearance. Pharmacogenetics 13:581–584CrossRefPubMed Leabman MK, Giacomini KM (2003) Estimating the contribution of genes and environment to variation in renal drug clearance. Pharmacogenetics 13:581–584CrossRefPubMed
31.
Zurück zum Zitat Mofo Mato EP, Guewo-Fokeng M, Essop MF, Oroma Owira PM (2018) Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes: a systematic review. Medicine 97:27e11349CrossRef Mofo Mato EP, Guewo-Fokeng M, Essop MF, Oroma Owira PM (2018) Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes: a systematic review. Medicine 97:27e11349CrossRef
32.
Zurück zum Zitat Barengolts E, Green SJ, Eisenberg Y et al (2018) Gut microbiota varies by opioid use, circulating leptin and oxytocin in African American men with diabetes and high burden of chronic disease. PLoS One 13(3):e0194171CrossRefPubMedPubMedCentral Barengolts E, Green SJ, Eisenberg Y et al (2018) Gut microbiota varies by opioid use, circulating leptin and oxytocin in African American men with diabetes and high burden of chronic disease. PLoS One 13(3):e0194171CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Burton JH, Johnson M, Johnson J, Hsia DS, Greenway FL, Heiman ML (2015) Addition of a gastrointestinal microbiome modulator to metformin improves metformin tolerance and fasting glucose levels. J Diabetes Sci Technol 9:808–814CrossRefPubMedPubMedCentral Burton JH, Johnson M, Johnson J, Hsia DS, Greenway FL, Heiman ML (2015) Addition of a gastrointestinal microbiome modulator to metformin improves metformin tolerance and fasting glucose levels. J Diabetes Sci Technol 9:808–814CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Brunkwall L, Orho-Melander M (2017) The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia 60:943–951CrossRefPubMedPubMedCentral Brunkwall L, Orho-Melander M (2017) The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia 60:943–951CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Henry RR, Frias JP, Walsh B et al (2018) Improved glycemic control with minimal systemic metformin exposure: effects of metformin delayed-release (metformin DR) targeting the lower bowel over 16 weeks in a randomized trial in subjects with type 2 diabetes. PLoS One 13(9):e0203946CrossRefPubMedPubMedCentral Henry RR, Frias JP, Walsh B et al (2018) Improved glycemic control with minimal systemic metformin exposure: effects of metformin delayed-release (metformin DR) targeting the lower bowel over 16 weeks in a randomized trial in subjects with type 2 diabetes. PLoS One 13(9):e0203946CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Duca FA, Cote CD, Rasmussen BA et al (2015) Metformin activates a duodenal AMPK-dependent pathway to lower hepatic glucose production in rats. Nat Med 21:506–511CrossRefPubMedPubMedCentral Duca FA, Cote CD, Rasmussen BA et al (2015) Metformin activates a duodenal AMPK-dependent pathway to lower hepatic glucose production in rats. Nat Med 21:506–511CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Duong JK, Furlong TJ, Roberts DM et al (2013) The role of metformin in metformin-associated lactic acidosis (MALA): case series and formulation of a model of pathogenesis. Drug Saf 36(9):733–746CrossRefPubMed Duong JK, Furlong TJ, Roberts DM et al (2013) The role of metformin in metformin-associated lactic acidosis (MALA): case series and formulation of a model of pathogenesis. Drug Saf 36(9):733–746CrossRefPubMed
39.
Zurück zum Zitat Maideen NMP, Jumale A, Balasubramaniam R (2017) Drug interactions of metformin involving drug transporter proteins. Adv Pharm Bull 7(4):501–505CrossRef Maideen NMP, Jumale A, Balasubramaniam R (2017) Drug interactions of metformin involving drug transporter proteins. Adv Pharm Bull 7(4):501–505CrossRef
40.
Zurück zum Zitat Li Q, Liu F, Zheng TS, Tang JL, Lu HJ, Jia WP (2010) SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin. Acta Pharmacol Sin 31:184–190CrossRefPubMedPubMedCentral Li Q, Liu F, Zheng TS, Tang JL, Lu HJ, Jia WP (2010) SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin. Acta Pharmacol Sin 31:184–190CrossRefPubMedPubMedCentral
Metadaten
Titel
Metformin and gut microbiota: their interactions and their impact on diabetes
verfasst von
Natalia G. Vallianou
Theodora Stratigou
Stylianos Tsagarakis
Publikationsdatum
01.06.2019
Verlag
Springer International Publishing
Erschienen in
Hormones / Ausgabe 2/2019
Print ISSN: 1109-3099
Elektronische ISSN: 2520-8721
DOI
https://doi.org/10.1007/s42000-019-00093-w

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Neu im Fachgebiet Innere Medizin

Vorsicht mit Glukokortikoiden bei Glomerulopathie

Auch niedrig dosierte Glukokortikoide zur Behandlung einer primären Glomerulopathie lassen offenbar die Infektionsgefahr steigen. In einer US-Studie hing das Risiko vor allem mit der kombinierten Anwendung von Immunsuppressiva zusammen.

Welche Krebserkrankungen bei Zöliakie häufiger auftreten

Eine große Kohortenstudie hat den Zusammenhang zwischen Zöliakie und gastrointestinalen Krebserkrankungen und inflammatorischen Krankheiten untersucht. Neben gastrointestinalen Tumoren ist auch ein nicht solider Krebs häufiger.

Adjuvanter PD-L1-Hemmer verhindert Rezidive bei Hochrisiko-Urothelkarzinom

Sind Menschen mit muskelinvasivem Urothelkarzinom für die neoadjuvante platinbasierte Therapie nicht geeignet oder sprechen sie darauf nicht gut an, ist Pembrolizumab eine adjuvante Alternative: Die krankheitsfreie Lebenszeit wird dadurch mehr als verdoppelt.

Einer von sieben Frauen macht die Menopause sehr zu schaffen

Von mäßigen bis schweren vasomotorischen Beschwerden sind 14,7% der Frauen in der Postmenopause betroffen. Das haben kanadische Forscherinnen in einer Subgruppenanalyse der WARM-Studie herausgefunden.

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

In diesem CME-Kurs können Sie Ihr Wissen zur EKG-Befundung anhand von zwölf Video-Tutorials auffrischen und 10 CME-Punkte sammeln.
Praxisnah, relevant und mit vielen Tipps & Tricks vom Profi.

Update Innere Medizin

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