Substances Produced by Gut Bacteria Modulate Drug Performance

They used a targeted gas chromatography – mass spectroscopy (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 could predict variation in statin low-density lipoprotein-cholesterol (LDL-C) lowering efficacy. Subjects in the study were participants in the national Cholesterol and Pharmacogenetics (CAP) study. For the current experiment, the investigators selected 100 people from the CAP study whose LDL-C fell dramatically as a result of taking simvastatin; 24 who had a fairly good response on the drug; and 24 who showed little benefit.

Results published in the October 13, 2011, online edition of the journal PLoS One revealed the identity of three secondary, bacterial-derived bile acids that contributed to the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine, and increased plasma concentration of simvastatin positively correlated with higher levels of these three secondary bile acids.

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. “This is personalized medicine – the effects of drugs and how we respond,” said first author Dr. Rima Kaddurah-Daouk, associate professor of psychiatry at Duke University. “We found that the benefit of statins could be partly related to the type of bacteria that lives in our guts. The reason we respond differently is not only our genetic makeup, but also our gut microbiome.”

“We really need to partner with diagnostic and pharmaceutical companies to target drugs for subpopulations,” said Dr. Kaddurah-Daouk. “… no doubt that metabolites from bacteria are playing an important role in regulating our systems. We are at a very early stage of understating this relationship, but eventually we could take a quick chemical assay and get a read on where we are metabolically.”

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