Interaction between the gut microbiota and oral antihyperglycemic drugs
https://doi.org/10.14341/probl12835
Abstract
The gut microbiome is the largest microbial habitat in the human body. The main functions include obtaining energy from complex food fibers, maturation and formation of the immune system, intestinal angiogenesis, restoration of epithelial damage to the intestine, development of the nervous system, protection against pathogens, etc. It is also known that a number of drugs can cause changes in the composition of the intestinal microflora, and intestinal bacteria, in turn, produce a number of enzymes and metabolites that can chemically change the structure of drugs, leading to more side effects, and in some cases to positive changes. In this review we present current evidence supporting the effects of microbiota in host-drug interactions, in particular, the reciprocal effects of gut microbiota and oral hypoglycemic drugs on each other. Gaining and evaluating knowledge in this area will help pave the way for the development of new microbiota-based strategies that can be used in the future to improve treatment outcomes for type 2 diabetes mellitus (T2D).
About the Authors
U. V. Buyvalenko
Endocrinology Research Centre
Russian Federation
Russian Federation
Uliana V. Buyvalenko
11 Dm.Ulyanova street, 117036 Moscow
E. V. Pokrovskaya
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Elena V. Pokrovskaya, MD, research associate
Moscow
SPIN-код: 8769-5010
Competing Interests:
Автор декларирует отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
References
1. Mutualizm: opredelenie, tipy i primery simbioticheskih otnoshenij. Priroda Mira. (In Russ.)]. [Internet]. Av. at: https://natworld.info/nauki-o-prirode/mutualizm-harakteristika-vidy-i-primery-vzaimootnoshenij. Link active on: 16.10.2021.
2. Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat Rev Microbiol. 2016;14(5):273-287. doi: https://doi.org/10.1038/nrmicro.2016.17
3. Judin SM, Egorova AM, Makarov VV. Analysis of human microbiota. Russian and foreign experience. Mezhdunarodnyj zhurnal prikladnyh i fundamental’nyh issledovanij. 2018;11-1:175-180. (In Russ.).
4. Yang B, Wang Y, Qian PY. Sensitivity and correlation of hypervariable regions in 16S rRNA genes in phylogenetic analysis. BMC Bioinformatics. 2016;17:135. doi: https://doi.org/10.1186/s12859-016-0992-y
5. Weersma RK, Zhernakova A, Fu J. Interaction between drugs and the gut microbiome. Gut. 2020;69(8):1510-1519. doi: https://doi.org/10.1136/gutjnl-2019-320204
6. Mallick H, Ma S, Franzosa EA, et al. Experimental design and quantitative analysis of microbial community multiomics. Genome Biol. 2017;18(1):228. doi: https://doi.org/10.1186/s13059-017-1359-z
7. Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577-1585. doi: https://doi.org/10.1007/s00125-017-4342-z
8. Pryor R, Cabreiro F. Repurposing metformin: an old drug with new tricks in its binding pockets. Biochem J. 2015;471(3):307-322. doi: https://doi.org/10.1042/BJ20150497
9. Stepensky D, Friedman M, Raz I, Hoffman A. Pharmacokinetic-pharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect. Drug Metab Dispos. 2002;30(8):861-868. doi: https://doi.org/10.1124/dmd.30.8.861
10. Bonora E, Cigolini M, Bosello O, et al. 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. 1984;9(1):47-51. doi: https://doi.org/10.1185/03007998409109558
11. Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262-266. doi: https://doi.org/10.1038/nature15766
12. Wu H, Esteve E, Tremaroli V, 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. 2017;23(7):850-858. doi: https://doi.org/10.1038/nm.4345
13. De Vadder F, Kovatcheva-Datchary P, Goncalves D, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156(1-2):84-96. doi: https://doi.org/10.1016/j.cell.2013.12.016
14. Cabreiro F, Au C, Leung KY, et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell. 2013;153(1):228-239. doi: https://doi.org/10.1016/j.cell.2013.02.035
15. Sahin M, Tutuncu NB, Ertugrul D, et al. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007;21(2):118-123. doi: https://doi.org/10.1016/j.jdiacomp.2005.10.005
16. Lee H, Ko G. Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol. 2014;80(19):5935-5943. doi: https://doi.org/10.1128/AEM.01357-14
17. Plovier H, Everard A, Druart C, et al. A purified membrane protein from Akkermansiamuciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107-113. doi: https://doi.org/10.1038/nm.4236
18. Bahne E, Hansen M, Brønden A, et al. Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin. Diabetes Obes Metab. 2016;18(10):955-961. doi: https://doi.org/10.1111/dom.12697
19. Napolitano A, Miller S, Nicholls AW, et al. Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoS One. 2014;9(7):e100778. doi: https://doi.org/10.1371/journal.pone.0100778
20. Christiansen CB, Gabe MBN, Svendsen B, et al. The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. Am J Physiol Gastrointest Liver Physiol. 2018;315(1):G53-G65. doi: https://doi.org/10.1152/ajpgi.00346.2017
21. Bauer PV, Duca FA, Waise TMZ, et al. Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway. Cell Metab. 2018;27(1):101-117.e5. doi: https://doi.org/10.1016/j.cmet.2017.09.019
22. Moreira GV, Azevedo FF, Ribeiro LM, et al. Liraglutide modulates gut microbiota and reduces NAFLD in obese mice. J Nutr Biochem. 2018;62:143-154. doi: https://doi.org/10.1016/j.jnutbio.2018.07.009
23. Zhang Q, Xiao X, Zheng J, et al. Featured article: Structure moderation of gut microbiota in liraglutide-treated diabetic male rats. Exp Biol Med (Maywood). 2018;243(1):34-44. doi: https://doi.org/10.1177/1535370217743765
24. Wang L, Li P, Tang Z, et al. Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment. Sci Rep. 2016;6:33251. doi: https://doi.org/10.1038/srep33251
25. Wang Z, Saha S, Van Horn S, et al. Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects. Endocrinol Diabetes Metab. 2017;1(1):e00009. doi: https://doi.org/10.1002/edm2.9
26. Olivares M, Neyrinck AM, Pötgens SA, et al. The DPP-4 inhibitor vildagliptin impacts the gut microbiota and prevents disruption of intestinal homeostasis induced by a Western diet in mice. Diabetologia. 2018;61(8):1838-1848. doi: https://doi.org/10.1007/s00125-018-4647-6
27. Baxter NT, Lesniak NA, Sinani H, et al. The Glucoamylase Inhibitor Acarbose Has a Diet-Dependent and Reversible Effect on the Murine Gut Microbiome. mSphere. 2019;4(1). doi: https://doi.org/10.1128/mSphere.00528-18
28. Gu Y, Wang X, Li J, Zhang Y, et al. Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment. Nat Commun. 2017;8(1):1785. doi: https://doi.org/10.1038/s41467-017-01682-2
29. Zhang X, Fang Z, Zhang C, et al. Effects of Acarbose on the Gut Microbiota of Prediabetic Patients: A Randomized, Double-blind, Controlled Crossover Trial. Diabetes Ther. 2017;8(2):293-307. doi: https://doi.org/10.1007/s13300-017-0226-y
30. Bai J, Zhu Y, Dong Y. Response of gut microbiota and inflammatory status to bitter melon (Momordica charantia L.) in high fat diet induced obese rats. J Ethnopharmacol. 2016;194:717-726. doi: https://doi.org/10.1016/j.jep.2016.10.043
31. Tomas J, Mulet C, Saffarian A, et al. High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine. Proc Natl Acad Sci U S A. 2016;113(40):E5934-E5943. doi: https://doi.org/10.1073/pnas.1612559113
32. Simes BC, MacGregor GG. Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician’s Guide. Diabetes Metab Syndr Obes. 2019;12:2125-2136. doi: https://doi.org/10.2147/DMSO.S212003
33. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi: https://doi.org/10.1056/NEJMoa1504720
34. Lee DM, Battson ML, Jarrell DK, et al. SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice. Cardiovasc Diabetol. 2018;17(1):62. doi: https://doi.org/10.1186/s12933-018-0708-x
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For citations:
Buyvalenko U.V., Pokrovskaya E.V. Interaction between the gut microbiota and oral antihyperglycemic drugs. Problems of Endocrinology. 2022;68(2):66-71. (In Russ.) https://doi.org/10.14341/probl12835
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