Gut Microbes

Gut Microbes; the first time Vayu Maini Rekdal manipulated microbes, he made a decent sourdough bread. At the time, young Maini Rekdal, and most people who head to the kitchen to whip up a salad dressing; pop popcorn, ferment vegetables, or caramelize onions; did not consider the crucial chemical reactions behind these concoctions.

Even more crucial are the reactions that happen after the plates are clean. When a slice of sourdough travels through the digestive system; but the trillions of microbes that live in our gut help the body break down that bread to absorb the nutrients. Since the human body cannot digest certain substances; all-important fiber, for example microbes step up to perform chemistry no human can.

“But this kind of microbial metabolism can also be detrimental,” said Maini Rekdal; a graduate student in the lab of Professor Emily Balskus and first-author on their new study published in Science. According to Maini Rekdal, gut microbes can chew up medications; too, often with hazardous side effects. “Maybe the drug is not going to reach its target in the body; maybe it’s going to be toxic all of a sudden, maybe it’s going to be less helpful,” Maini Rekdal said.

Gut microbes and medications

In their study, Balskus, Maini Rekdal, and their collaborators at the University of California San Francisco; describe one of the first concrete examples of how the microbiome; but can interfere with a drug’s intended path through the body. Focusing on levodopa (L-dopa), the primary treatment for Parkinson’s disease; they identified which bacteria out of the trillions of species is responsible for degrading the drug; and how to stop this microbial interference.

Parkinson’s disease attacks nerve cells in the brain that produce dopamine; without which the body can suffer tremors, muscle rigidity, and problems with balance and coordination. L-dopa delivers dopamine to the brain to relieve symptoms. But only about 1 to 5% of the drug actually reaches the brain.

L-dopa metabolism

This number—and the drug’s efficacy—varies widely from patient to patient. Since the introduction of L-dopa in the late 1960s, researchers have known that the body’s enzymes (tools that perform necessary chemistry); can break down L-dopa in the gut, preventing the drug from reaching the brain. So, the pharmaceutical industry introduced a new drug; carbidopa, to block unwanted L-dopa metabolism. Taken together, the treatment seemed to work.

“Even so,” Maini Rekdal said, “there’s a lot of metabolism that’s unexplained, and it’s very variable between people.” That variance is a problem; Not only is the drug less effective for some patients, but when L-dopa is transformed into dopamine outside the brain; the compound can cause side effects, including severe gastrointestinal distress and cardiac arrhythmias. If less of the drug reaches the brain, patients are often given more to manage their symptoms; potentially exacerbating these side effects.