Gut Microbiome Predicts Statins Response and Side Effects

Researchers in Seattle have discovered that the composition of the patient’s gut microbiome is predictive of their response to statins, which lower cholesterol and comprise the most prescribed category of prescription drugs in America. The findings offer promising avenues for optimizing precision statin treatments for individual patients.

More than 40 million Americans take statins. While the lipid-lowering drugs have been shown to effectively reduce cholesterol levels and stroke and heart attack risk, they do not work the same for everyone. Side effects of statin use can also include an increased risk of developing type 2 diabetes.

Researchers from Institute for Systems Biology (ISB) have traced these differences in statin response to variations in the human microbiome—to the point of being able to predict the efficacy of statins and magnitude of negative side effects based on its composition. 

“Specifically, we found that a Bacteroides-enriched microbiome with lower levels of diversity was associated with the strongest LDL-lowering response to statins, but also coincided with the greatest disruption to blood glucose levels,” says Dr. Tomasz Wilmanski, lead author of the study.

The team also found that individuals with a Ruminococcaceae-enriched microbiome were protected from the negative side effects of statins on insulin resistance while also showing a clear low-density lipoprotein (LDL)-lowering response.

The initial discovery of variable statin effects on both cholesterol and blood glucose markers was made by building statistical models with microbiome, metabolome, human genome, and clinical records from an American cohort of more than 1,800 people.  Next, Wilmanski and colleagues validated the results in an independent European cohort of nearly 1,000 people.   

The genetic fingerprint of a patient, which includes known genetic markers of statin treatment response, has already been leveraged in the clinic to guide personalized statin treatment regimes. In this study, the authors found that the variability in statin responses explained by the microbiome were completely independent of the variability captured by the genome. “It’s a completely different axis of variability, so we’re able to build models including both genetics and the gut microbiome to improve our statin response predictions,” Wilmanski said. “The genome and the microbiome, together, appear to provide a more comprehensive and complementary picture of personalized drug responses.”

A logical follow-up to this work is a clinical trial, according to ISB Assistant Professor and coauthor Dr. Sean Gibbons.  “It would be great to take this knowledge about the genome and the microbiome and predict personalized dosing regimens for a cohort of patients, and then follow these patients forward in time, tracking their metabolic health and their LDL cholesterol levels, to show that this population of patients undergoing a precision intervention do better than a control group of patients who are getting what is normally prescribed,” he says.  

The findings were published recently in the journal Med.