Skip to main content

Enteric microbiome metabolites correlate with response to simvastatin treatment.

Publication ,  Journal Article
Kaddurah-Daouk, R; Baillie, RA; Zhu, H; Zeng, Z-B; Wiest, MM; Nguyen, UT; Wojnoonski, K; Watkins, SM; Trupp, M; Krauss, RM
Published in: PLoS One
2011

Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could provide valuable information about treatment outcomes and could contribute to a more personalized approach to therapy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

10

Start / End Page

e25482

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Simvastatin
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Organic Anion Transporters
  • Models, Biological
  • Middle Aged
  • Metagenome
  • Metabolomics
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kaddurah-Daouk, R., Baillie, R. A., Zhu, H., Zeng, Z.-B., Wiest, M. M., Nguyen, U. T., … Krauss, R. M. (2011). Enteric microbiome metabolites correlate with response to simvastatin treatment. PLoS One, 6(10), e25482. https://doi.org/10.1371/journal.pone.0025482
Kaddurah-Daouk, Rima, Rebecca A. Baillie, Hongjie Zhu, Zhao-Bang Zeng, Michelle M. Wiest, Uyen Thao Nguyen, Katie Wojnoonski, Steven M. Watkins, Miles Trupp, and Ronald M. Krauss. “Enteric microbiome metabolites correlate with response to simvastatin treatment.PLoS One 6, no. 10 (2011): e25482. https://doi.org/10.1371/journal.pone.0025482.
Kaddurah-Daouk R, Baillie RA, Zhu H, Zeng Z-B, Wiest MM, Nguyen UT, et al. Enteric microbiome metabolites correlate with response to simvastatin treatment. PLoS One. 2011;6(10):e25482.
Kaddurah-Daouk, Rima, et al. “Enteric microbiome metabolites correlate with response to simvastatin treatment.PLoS One, vol. 6, no. 10, 2011, p. e25482. Pubmed, doi:10.1371/journal.pone.0025482.
Kaddurah-Daouk R, Baillie RA, Zhu H, Zeng Z-B, Wiest MM, Nguyen UT, Wojnoonski K, Watkins SM, Trupp M, Krauss RM. Enteric microbiome metabolites correlate with response to simvastatin treatment. PLoS One. 2011;6(10):e25482.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

10

Start / End Page

e25482

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Simvastatin
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Organic Anion Transporters
  • Models, Biological
  • Middle Aged
  • Metagenome
  • Metabolomics
  • Male