Advertisement

Journal of Microbiology

, Volume 56, Issue 12, pp 886–892 | Cite as

Comparative analysis of the gut microbiota in distinct statin response patients in East China

  • Baoqing Sun
  • Luming Li
  • Xinfu ZhouEmail author
Article
  • 51 Downloads

Abstract

Statin response shows great interindividual variations. Recently, emerging studies have shown that gut microbiota is linked to therapeutic responses to drugs, including statins. However, the association between the gut bacteria composition and statin response is still unclear. In this study, gut microbiota of 202 hyperlipidemic patients with statin sensitive (SS) response and statin resistant (SR) response in East China were investigated by high throughput sequencing to compare the gut bacteria composition and biodiversity in distinct statin response patients. Higher biodiversity was detected in Group SS than Group SR. Specifically, group SS showed significantly increased proportion of genera Lactobacillus (P = 0.001), Eubacterium (P = 0.004), Faecalibacterium (P = 0.005), and Bifidobacterium (P = 0.002) and decreased proportion of genus Clostridium (P = 0.001) compared to Group SR. The results indicated that higher gut biodiversity was associated with statin sensitive response. The increased genera Lactobacillus, Eubacterium, Faecalibacterium, Bifidobacterium, and decreased genus Clostridium in patient gut microbiota may predict patient's statin response, and hence may guide statin dosage adjustments.

Keywords

hyperlipidemia gut microbiota statin response microbial diversity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahn, Y.T., Kim, G.B., Lim, K.S., Baek, Y.J., and Kim, H.U. 2003. Deconjugation of bile salts by Lactobacillus acidophilus isolates. Int. Dairy J. 13, 303–311.CrossRefGoogle Scholar
  2. Arrigoni, E., Re, M.D., Fidilio, L., Fogli, S., Danesi, R., and Paolo, A.D. 2017. Pharmacogenetic foundations of therapeutic efficacy and adverse events of statins. Int. J. Mol. 18, 104.CrossRefGoogle Scholar
  3. Barber, M.J., Mangravite, L.M., Hyde, C.L., Chasman, D.I., Smith, J.D., Mccarty, C.A., Li, X., Wilke, R.A., Rieder, M.J., and Williams, P.T. 2010. Genome-wide association of lipid-lowering response to statins in combined study populations. PLoS One 5, e9763.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Barber, M.J., Mangravite, L.M., Hyde, C.L., Chasman, D.I., Smith, J.D., Mccarty, C.A., Li, X., Wilke, R.A., Rieder, M.J., and Williams, P.T. 2012. Genome-wide association of lipid-lowering response to statins in combined study populations. PLoS One 5, e9763.CrossRefGoogle Scholar
  5. Bellosta, S., Paoletti, R., and Corsini, A. 2004. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 109, III50.CrossRefPubMedGoogle Scholar
  6. Blynskaya, E.V., Chernova, O.A., and Alekseev, V.K. 2012. Comparative pharmacokinetic study of normostatin tablets. Moscow Univ. Chem. Bull. 67, 136–141.CrossRefGoogle Scholar
  7. Bordoni, A., Amaretti, A., Leonardi, A., Boschetti, E., Danesi, F., Matteuzzi, D., Roncaglia, L., Raimondi, S., and Rossi, M. 2013. Cholesterol- lowering probiotics: in vitro selection and in vivo testing of bifidobacteria. Appl. Microbiol. Biotechnol. 97, 8273–8281.CrossRefPubMedGoogle Scholar
  8. Brown, A.C. and Valiere, A. 2004. Probiotics and medical nutrition therapy. Nutr. Clin. Care 7, 56.PubMedPubMedCentralGoogle Scholar
  9. Burke, D.G., Fouhy, F., Harrison, M.J., Rea, M.C., Cotter, P.D., O’Sullivan, O., Stanton, C., Hill, C., Shanahan, F., and Plant, B.J. 2017. The altered gut microbiota in adults with cystic fibrosis. BMC Microbiol. 17, 58.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chan, Y.K., Brar, M.S., Kirjavainen, P.V., Chen, Y., Peng, J., Li, D., Leung, F.C., and El-Nezami, H. 2016. High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE(-/-) mice. BMC Microbiol. 16, 264.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Clarke, S.F., Murphy, E.F., O’Sullivan, O., Lucey, A.J., Humphreys, M., Hogan, A., Hayes, P., O’Reilly, M., Jeffery, I.B., and Woodmartin, R. 2014. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63, 1913.CrossRefPubMedGoogle Scholar
  12. Clendening, J.W., Pandyra, A., Li, Z., Boutros, P.C., Martirosyan, A., Lehner, R., Jurisica, I., Trudel, S., and Penn, L.Z. 2010. Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma. Blood 115, 4787–4797.CrossRefPubMedGoogle Scholar
  13. Cruz-Domínguez, M.P., Cortés, D.H., Zarate, A., Tapia-González, M.L., Alvarez-Acosta, S., Damasio, L., and Manuel-Apolinar, L. 2014. Relationship of ghrelin, acid uric and proinflammatory adipocytokines in different degrees of obesity or diabetes. Int. J. Clini. Exp. Med. 7, 1435.Google Scholar
  14. Desantis, T.Z., Hugenholtz, P., Larsen, N., Rojas, M., Brodie, E.L., Keller, K., Huber, T., Dalevi, D., Hu, P., and Andersen, G.L. 2006. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 72, 5069–5072.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Edgar, R.C., Haas, B.J., Clemente, J.C., Christopher, Q., and Rob, K. 2011. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics 27, 2194–2200.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Enright, E.F., Gahan, C.G.M., Joyce, S.A., and Griffin, B.T. 2016. The impact of the gut microbiota on drug metabolism and clinical outcome. Yale J. Biol. Med. 89, 375–382.PubMedPubMedCentralGoogle Scholar
  17. Fåk, F. and Bäckhed, F. 2012. Lactobacillus reuteri prevents dietinduced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice. PLoS One 7, e46837.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Gismondo, M.R., Drago, L., and Lombardi, A. 1999. Review of probiotics available to modify gastrointestinal flora. Int. J. Antimicrob. Agents 12, 287–292.CrossRefPubMedGoogle Scholar
  19. Huang, Y. and Zheng, Y. 2010. The probiotic Lactobacillus acidophilus reduces cholesterol absorption through the down-regulation of Niemann-Pick C1-like 1 in Caco-2 cells. Br. J. Nutr. 103, 473–478.CrossRefPubMedGoogle Scholar
  20. Jakobsson, H.E., Abrahamsson, T.R., Jenmalm, M.C., Harris, K., Quince, C., Jernberg, C., Björkstén, B., Engstrand, L., and Andersson, A.F. 2014. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut 63, 559.CrossRefPubMedGoogle Scholar
  21. Jawaid, S., Gertz, M., Corsino, C., Cheung, J., Seidle, H., and Couch, R.D. 2010. Human hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity. Indian J. Biochem. Biophys. 47, 331.PubMedGoogle Scholar
  22. Kaddurahdaouk, R., Baillie, R.A., Zhu, H., Zeng, Z.B., Wiest, M.M., Nguyen, U.T., Wojnoonski, K., Watkins, S.M., Trupp, M., and Krauss, R.M. 2011. Enteric microbiome metabolites correlate with response to simvastatin treatment. PLoS One 6, e25482.CrossRefGoogle Scholar
  23. Karlsson, F.H., Fåk, F., Nookaew, I., Tremaroli, V., Fagerberg, B., Petranovic, D., Bäckhed, F., and Nielsen, J. 2012. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat. Commun. 3, 1245.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Kumar, M., Nagpal, R., Kumar, R., Hemalatha, R., Verma, V., Kumar, A., Chakraborty, C., Singh, B., Marotta, F., and Jain, S. 2012. Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases. Exp. Diabetes Res. 2012, 902917.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Law, M.R., Wald, N.J., and Rudnicka, A.R. 2003. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 326, 1423.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Leusink, M., Onland-Moret, N.C., de Bakker, P.I., De, B.A., and Ah, M.V.D.Z. 2016. Seventeen years of statin pharmacogenetics: a systematic review. Pharmacogenomics 17, 163.CrossRefPubMedGoogle Scholar
  27. Li, L., Buhman, K.K., Hartman, P.A., and Beitz, D.C. 1995. Hypocholesterolemic effect of Eubacterium coprostanoligenes ATCC 51222 in rabbits. Lett. Appl. Microbiol. 20, 137–140.CrossRefPubMedGoogle Scholar
  28. Mangravite, L.M., Thorn, C.F., and Krauss, R.M. 2006. Clinical implications of pharmacogenomics of statin treatment. Pharmacogenomics J. 6, 360–374.CrossRefPubMedGoogle Scholar
  29. Manichanh, C., RigottierGois, L., Bonnaud, E., Gloux, K., Pelletier, E., Frangeul, L., Nalin, R., Jarrin, C., Chardon, P., and Marteau, P. 2006. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55, 205–211.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Marteau, P.R., De, V.M., Cellier, C.J., and Schrezenmeir, J. 2001. Protection from gastrointestinal diseases with the use of probiotics. Am. J. Clin. Nutr. 73, 430S–436S.CrossRefGoogle Scholar
  31. Mega, J.L., Morrow, D.A., Brown, A., Cannon, C.P., and Sabatine, M.S. 2009. Identification of genetic variants associated with response to statin therapy. Arterioscler. Thromb. Vasc. Biol. 29, 1310.CrossRefPubMedGoogle Scholar
  32. Møller, K.K., Rattray, F.P., and Ardö, Y. 2013. Application of selected lactic acid bacteria and coagulant for improving the quality of low-salt cheddar cheese: chemical, microbiological and rheological evaluation. Int. Dairy. J. 33, 163.CrossRefGoogle Scholar
  33. Moore, V. 2008. The gastrointestinal microbiota as a site for the biotransformation of drugs. Int. J. Pharm. 363, 1–25.CrossRefPubMedGoogle Scholar
  34. Munukka, E., Rintala, A., Toivonen, R., Nylund, M., Yang, B., Takanen, A., Hänninen, A., Vuopio, J., Huovinen, P., and Jalkanen, S. 2017. Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice. ISME J. 11, 1667.CrossRefPubMedPubMedCentralGoogle Scholar
  35. O’Neill, F.H., Patel, D.D., Knight, B.L., Neuwirth, C.K., Bourbon, M., Soutar, A.K., Taylor, G.W., Thompson, G.R., and Naoumova, R.P. 2001. Determinants of variable response to statin treatment in patients with refractory familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 21, 832–837.CrossRefPubMedGoogle Scholar
  36. Oh, J., Ban, M.R., Miskie, B.A., Pollex, R.L., and Hegele, R.A. 2007. Genetic determinants of statin intolerance. Lipids Health Dis. 6, 7.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Postmus, I., Trompet, S., Deshmukh, H.A., Barnes, M.R., Li, X., Warren, H.R., Chasman, D.I., Zhou, K., Arsenault, B.J., and Donnelly, L.A. 2014. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat. Commun. 5, 5068.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Ramasamy, K., Shafawi, Z.M., Mani, V., Wan, H.Y., and Majee, A.B.A. 2012. Hypocholesterolaemic effects of probiotics. In Complementary therapies for the contemporary healthcare. Intech.Google Scholar
  39. Reiner, Z. 2014. Resistance and intolerance to statins. Nutr. Metab. Cardiovasc. Dis. 24, 1057–1066.CrossRefPubMedGoogle Scholar
  40. Reis, S.A., Conceição, L.L., Rosa, D.D., Siqueira, N.P., and Peluzio, M.C. 2017. Mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotics. Nutr. Res. Rev. 30, 36–49.CrossRefPubMedGoogle Scholar
  41. Ren, D., Ling, L.A.W.S., Young, J.W., and Beitz, D.C. 1996. Mechanism of cholesterol reduction to coprostanol by Eubacterium coprostanoligenes ATCC 51222. Steroids 61, 33–40.CrossRefPubMedGoogle Scholar
  42. Rodrigues, A.C. 2010. Efflux and uptake transporters as determinants of statin response, expert opinion on drug metabolism & toxicology, informa healthcare. Expert. Opin. Drug Metab. Toxicol. 6, 621–632.CrossRefPubMedGoogle Scholar
  43. Salaj, R., Štofilová, J., Šoltesová, A., Hertelyová, Z., Hijová, E., Bertková, I., Strojný, L., Kružliak, P., and Bomba, A. 2013. The effects of two Lactobacillus plantarum strains on rat lipid metabolism receiving a high fat diet. Sci. World J. 2013, 135142.CrossRefGoogle Scholar
  44. Salminen, S., Isolauri, E., and Onnela, T. 2004. Gut flora in normal and disordered states. Chemotherapy 41 Suppl 1, 5.CrossRefGoogle Scholar
  45. Sarkar, S. 2003. Potential of acidophilus milk to lower cholesterol. Nur. Food Sci. 33, 273–277.CrossRefGoogle Scholar
  46. Shanahan, F. 2010. Probiotics in perspective. Gastroenterology 139, 1808–1812.CrossRefPubMedGoogle Scholar
  47. Sirtori, C.R., Mombelli, G., Triolo, M., and Laaksonen, R. 2012. Clinical response to statins: mechanism(s) of variable activity and adverse effects. Ann. Med. 44, 419–432.CrossRefPubMedGoogle Scholar
  48. Stancu, C.S., Sanda, G.M., Deleanu, M., and Sima, A.V. 2014. Probiotics determine hypolipidemic and antioxidant effects in hyperlipidemic hamsters. Mol. Nutr. Food Res. 58, 559.CrossRefPubMedGoogle Scholar
  49. Tahri, K., Grill, J.P., and Schneider, F. 1996. Bifidobacteria strain behavior toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 33, 187.CrossRefPubMedGoogle Scholar
  50. Tok, E. and Aslim, B. 2010. Cholesterol removal by some lactic acid bacteria that can be used as probiotic. Microbiol. Immunol. 54, 257–264.PubMedGoogle Scholar
  51. Turroni, F., Peano, C., Pass, D.A., Foroni, E., Severgnini, M., Claesson, M.J., Kerr, C., Hourihane, J., Murray, D., and Fuligni, F. 2012. Diversity of bifidobacteria within the infant gut microbiota. PLoS One 7, e36957.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Usman, and Hosono, A. 2000. Effect of administration of Lactobacillus gasseri on serum lipids and fecal steroids in hypercholesterolemic rats. J. Dairy Sci. 83, 1705.CrossRefPubMedGoogle Scholar
  53. Wang, Q., Garrity, G.M., Tiedje, J.M., and Cole, J.R. 2007. Naïve bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 73, 5261–5267.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Yoo, D.H., Kim, I.S., Van Le, T.K., Jung, I.H., Yoo, H.H., and Kim, D.H. 2014. Gut microbiota-mediated drug interactions between lovastatin and antibiotics. Drug Metab. Dispos. 42, 1508–1513.CrossRefPubMedGoogle Scholar
  55. Zanotti, I., Turroni, F., Piemontese, A., Mancabelli, L., Milani, C., Viappiani, A., Prevedini, G., Sanchez, B., Margolles, A., and Elviri, L. 2015. Evidence for cholesterol-lowering activity by Bifidobacterium bifidum PRL2010 through gut microbiota modulation. Appl. Microbiol. Biotechnol. 99, 6813–6829.CrossRefPubMedGoogle Scholar
  56. Zhou, Q. and Liao, J.K. 2010. Pleiotropic effects of statins. Circ. J. 74, 818–826.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Weihai Municipal HospitalWeihaiP. R. China

Personalised recommendations