Bugs & Drugs – The entanglement in our guts

In the pharma hall of fame, statins are a rockstar drug. 

Hundreds of millions of patients are prescribed statins for ‘high cholesterol’ each year. Statins slow down the mechanism our liver employs to produce cholesterol and thus decrease the risk of heart attacks and strokes.

But there is a problem. Responses to statins vary widely from person to person. This results in significant consequences for the patient- what dose is right? And how should this change over time? Current dosage guidelines are based on body weight, cholesterol levels and then adjusting doses based on response. Managing side effects like liver inflammation by adjusting the dose is unfortunately more art than science and we doctors often just have to guess.

This is where the data from the gut microbiome may be invaluable. The gut microbiome was previously shown to influence metformin, a common diabetes medicine’s effectiveness, and this seems similar to statins. Researchers at the Institute for Systems Biology in Seattle found several microbiome traits correlating with statin on-target and adverse effects. First, they discovered that a particular blood marker (HMG) was a promising indicator of statin effectiveness. They then linked this blood marker (serving as a proxy for statin responses) to certain microbiome traits.

The findings are – Gut microbiomes with a Bacteroides-enriched (type of bacteria in the gut) and diversity-depleted (fewer types of different bacteria) were associated with more intense statin responses - in terms of both on-target and adverse effects.

But what does this all mean?

Firstly, statin doses could be lowered for the highly responsive group (low diversity + high Bacteroides), achieving sufficient on-target effects while minimising adverse effects.

On the other hand, doses could be immediately increased for the less responsive group (high diversity + low Bacteroides) to achieve sufficient on-target effects without any delays.

The gut microbiome field is evolving. New insights are being discovered rapidly. Soon enough we will test our bugs to figure out the right drugs.

Written by:
Dr Saishreyas Sundarajoo