Gut microbiome composition predictive of pati

SEATTLE — More than 40 million Americans take statins, the most common type of prescription drug. Although statins have been shown to be effective in lowering cholesterol levels and reducing the risk of stroke and heart attack, they do not work the same way for everyone, and the side effects of Statin use includes an increased risk of developing type 2 diabetes.

Researchers from the Institute for Systems Biology have shown that the different patient responses to statins can be explained by variation in the human microbiome. The results were published today in the journal Mediumand offer promising avenues for optimizing precision statin therapy for individual patients.

The research team found that the composition and diversity of the gut microbiome predicts the effectiveness of statins and the extent of negative side effects.

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

The team also found that people with Ruminococcaceae enriched microbiome were protected from the negative side effects of statins on insulin resistance while showing a clear LDL reduction response.

Wimanski and colleagues built statistical models with the microbiome, metabolome, human genome, and clinical records of a US cohort of over 1,800 people and made their first findings on the variable effects of statins on markers of cholesterol and blood sugar. Then, they validated their results in an independent European cohort of nearly 1,000 people.

The unique combination of microbiome and genomic information in this study provides exciting new insights into potential approaches to precision drug treatments.

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

A logical follow-up to this work is a clinical trial. “It would be great to take this knowledge of the genome and microbiome and predict personalized dosing regimens for a cohort of patients, and then follow those patients over time, tracking their metabolic health and LDL cholesterol levels, to show that this population of patients undergoing precision intervention do better than a control group of patients who receive what is normally prescribed,” said ISB Assistant Professor Dr. Sean Gibbons, corresponding author of the paper.

About VSI

The Institute for Systems Biology (ISB) is a nonprofit biomedical research organization based in Seattle. We focus on some of the most pressing issues in human health, including aging, brain health, cancer, COVID-19 and many infectious diseases. ISB is a subsidiary of Providence, one of the nation’s largest nonprofit health care systems. Follow us at www.isbscience.org and on YouTube, Facebook, LinkedIn and Twitter.


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