Featured Research

from universities, journals, and other organizations

Bacterial blockade: How gut microbes can inactivate cardiac drugs

Date:
July 25, 2013
Source:
Harvard University
Summary:
Researchers have identified a pair of genes which appear to be responsible for allowing a specific strain of bacteria in the human gut to break down Lanoxin -- a widely prescribed cardiac drug -- into an inactive compound, as well as a possible way to turn the process off.

Artist's rendering of bacteria (stock image).
Credit: fotoliaxrender / Fotolia

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.

Related Articles


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."


Story Source:

The above story is based on materials provided by Harvard University. The original article was written by Peter Reuell. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. J. Haiser, D. B. Gootenberg, K. Chatman, G. Sirasani, E. P. Balskus, P. J. Turnbaugh. Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta. Science, 2013; 341 (6143): 295 DOI: 10.1126/science.1235872

Cite This Page:

Harvard University. "Bacterial blockade: How gut microbes can inactivate cardiac drugs." ScienceDaily. ScienceDaily, 25 July 2013. <www.sciencedaily.com/releases/2013/07/130725161357.htm>.
Harvard University. (2013, July 25). Bacterial blockade: How gut microbes can inactivate cardiac drugs. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2013/07/130725161357.htm
Harvard University. "Bacterial blockade: How gut microbes can inactivate cardiac drugs." ScienceDaily. www.sciencedaily.com/releases/2013/07/130725161357.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins