Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bacterial blockade

26.07.2013
Research explains how gut microbes can inactivate cardiac drugs

For decades, doctors have understood that microbes in the human gut can influence how certain drugs work in the body — by either activating or inactivating specific compounds — but questions have remained about exactly how the process works.

Harvard scientists are now beginning to provide those answers.

In a paper published July 19 in Science, Peter Turnbaugh, a Bauer Fellow at the Center for Systems Biology in the Faculty of Arts and Sciences (FAS), and Henry Haiser, a postdoctoral fellow, identify a pair of genes that appear to be responsible for allowing a specific strain of bacteria to break down a widely prescribed cardiac drug into an inactive compound, as well as a possible way to turn the process off.

“The traditional view of microbes in the gut relates to how they influence the digestion of our diet,” Turnbaugh said. “But we also know that there are over 40 different drugs that can be influenced by gut microbes. What’s really interesting is that although this has been known for decades, we still don’t really understand which microbes are involved or how they might be processing these compounds.”

To answer those questions, Turnbaugh and his colleagues chose to focus on digoxin, one of the oldest known cardiac glycosides. The medicine is typically prescribed to treat heart failure and cardiac arrhythmia.

“It’s one of the few drugs that, if you look in a pharmacology textbook, it will say that it’s inactivated by gut microbes,” Turnbaugh said. “John Lindenbaum’s group at Columbia showed that in the 1980s. They found that a single bacterial species, Eggerthella lenta, was responsible.”

Researchers in the earlier study also tried — but failed — to show that testing bacterial samples from a person’s gut could be used to predict whether the drug might be inactivated.

“To some degree the research was stalled there for a number of years, and the findings in our paper help to explain why,” Turnbaugh said. “Originally, it was hoped that we would simply be able to measure the amount of E. lenta in a person’s gut and predict whether the drug would be inactivated, but it’s more complicated than that.”

Beginning with lab-grown samples of E. lenta — some cultured in the presence of digoxin, some in its absence — Turnbaugh and Haiser tested to see if certain genes were activated by the presence of the drug.

“We identified two genes that were expressed at very low levels in the absence of the drug, but when you add the drug to the cultures … they come on really strong,” Turnbaugh said. “What’s encouraging about these two genes is that they both express what are called cytochromes — enzymes that are likely capable of converting digoxin to its inactive form.”

Though he warned that more genetic testing is needed before the results are definitive, Turnbaugh said other experiments support these initial findings.

The researchers found only a single strain of E. lenta — the only one that contained the two genes they had earlier identified — was capable of inactivating digoxin. In tests using human samples, bacterial communities that were able to inactivate the drug also showed high levels of these genes

“We were able to confirm that simply looking for the presence of E. lenta is not enough to predict which microbial communities inactivate digoxin,” Turnbaugh said. “We found detectable E. lenta colonization in all the human fecal samples we analyzed. But by testing the abundance of the identified genes we were able to reliably predict whether or not a given microbial community could metabolize the drug.”

In addition to being able to predict whether a given microbial community would inactivate the drug, Turnbaugh and colleagues identified a possible way to halt the process.

“It was previously shown that in the lab E. lenta grows on the amino acid arginine and that as you supply more and more arginine, you inhibit digoxin inactivation,” he said.

Tests conducted with mice showed that animals fed a diet high in protein, and thereby arginine, had higher levels of the drug in their blood than mice fed a zero-protein diet.

“We think that this could potentially be a way to tune microbial drug metabolism in the gut,” Turnbaugh said. “Our findings really emphasize the need to see if we can predict or prevent microbial drug inactivation in cardiac patients. If successful, it may be possible someday to recommend a certain diet, or to co-administer the drug with an inhibitor like arginine, ensuring a more reliable dosage.”

Peter Reuell | EurekAlert!
Further information:
http://www.fas.harvard.edu

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>