Gut microbes may gobble up the medications we take before drugs have a chance to reach their targets, a new study suggests.
Our guts are essential to our ability to make use of all kinds of nutrients that wouldn’t otherwise be available to our systems – and the more we learn about the microbiome, the more it becomes clear it’s essential to our overall health.
But the trillions of gut bacteria that we coexist with (mostly) peacefully can work against us sometimes, too.
Researchers at Harvard University discovered that some gut bacteria can break down drugs, like those used to treat Parkinson’s disease, rendering them ineffective, or even toxic.
Their discovery may one day help scientists develop drugs that block or bypass the gut’s attempts to devour drugs before they hit their targets.
Americans spend hundreds of billions of dollars on medicine every year – but that expenditure is no guarantee that the drugs we take will be effective.
Medications are, bottom line, not 100 percent effective, and how well they work varies from person to person, based on a nearly infinite array of factors, including other medications, body weight, and, we now know, two types of metabolism.
Any drug that’s taken orally – in the form of a pill, capsule or liquid – has to travel through the gastrointestinal system.
But in order to reach a target that is outside the gastrointestinal tract, the drug has to designed to withstand the human body’s attempts to digest it.
Already, we knew that drugs had to have coatings or other features to make them impermeable to gastric acids innate to the human body, which allow us to break down and glean energy from most of the food we eat.
However, as we learn more about the trillions of other life forms – namely, bacteria – that live in the human gut, scientists have begun to see that those bacteria act as ‘brilliant chemistry’ to break down other things our body’s wouldn’t otherwise be able to, including fiber, and some drugs.
After discovering how microbes act on a heart failure medication, Harvard researchers turned to a Parkinson’s medication to see how what else gut flora might do to drugs.
They tested gut microbe activity on a drug called L-dopa.
L-dopa is a treatment for Parkinson’s, an incurable neurological condition marked by a dopamine deficiency.
The drug is meant to replace some of the neurotransmitter in a patient’s brain, but prior study has shown that only between one and five percent of the drug’s payload actually crosses the blood-brain barrier and reaches its target, so dosage has to be high, and the effects are less dramatic than doctors and patients may hope.
It’s now combined with another drug that keeps the body from metabolizing dopamine, but the scientists still wanted to know where the dopamine was going otherwise.
‘There’s a lot of metabolism that’s unexplained, and it’s very variable between people said Vayu Maini Rekdal, first study author.
Antibiotics have in the past effectively blocked the body from breaking down dopamine, so the researchers suspected that the gut bacteria those drugs wipe out might be, in turn wiping out dopamine.
Rekdal and his team tested L-dopa against a library of human gut bacteria species.
They discovered one in particular that gobbled up L-dopa every single time the scientists offered it up.
At present, that’s bad news for L-dopa, but it gives scientists a tool to develop better defenses of the important drug against the gut’s metabolism.
‘In the drug development process, we should think about these microbe chemists and what molecules they might be susceptible to when we start to develop drugs,’ said Rekdal, a PhD candidate.
And, he suggests, scientists should ask themselves: ‘Can we use microbial enzymes and profiles as biomarkers to try to tune and predict how much you need’ of a given drug to treat an individual with minimal side effects.
His hope is that drug-makers can develop new molecules that would stop the particular species of microbe he and his team developed from eating up L-dopa and, hopefully, someday make a more effective version of the drug.
Their study, published in the Journal Science, also led to a happy accidental secondary discovery: another piece of the gut-brain connection puzzle.
‘Our discovery of an organism that is chewing up dopamine…raises a quesitons about how these microbes interact with our nervous system,’ said Rekdal.
‘We don’t know yet what this means, but it reveals a molecular link between our nervous system and microbes.’
13 June 2019