Navigation Links
Bacterial blockade
Date:7/25/2013

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 long remained about exactly how the process works.

Harvard scientists are now beginning to provide those answers.

In a July 19th paper published in Science, Peter Turnbaugh, a Bauer Fellow at Harvard's Faculty of Arts and Sciences (FAS) Center for Systems Biology, and Henry Haiser, a postdoctoral fellow, identify a pair of genes which 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 colleagues chose to focus on digoxin, one of the oldest-known cardiac glycosides, which 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."

As part of that earlier study, researchers also tried but failed to show whether testing bacterial samples taken 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 culturesthey 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'd 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 compared to 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."


'/>"/>

Contact: Peter Reuell
preuell@fas.harvard.edu
617-496-8070
Harvard University
Source:Eurekalert

Related biology news :

1. Study finds depletion of alveolar macrophages linked to bacterial super-infections
2. New methods to visualize bacterial cell-to-cell communication
3. UT study: Chemical in antibacterial soaps may harm nursing babies
4. Spinning up antibacterial silver on glass
5. Bacterial DNA may integrate into human genome more readily in tumor tissue
6. HIV-derived antibacterial shows promise against drug-resistant bacteria
7. Metabolic model of E. coli reveals how bacterial growth responds to temperature change
8. Bacterial security agents go rogue
9. Secrets of bacterial slime revealed
10. Sequencing tracks animal-to-human transmission of bacterial pathogens
11. Antibacterial proteins molecular workings revealed
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/17/2017)... Florida , April 17, 2017 NXT-ID, ... technology company, announces the filing of its 2016 Annual Report on ... and Exchange Commission. ... on Form 10-K is available in the Investor Relations section of ... as on the SEC,s website at http://www.sec.gov . ...
(Date:4/13/2017)... According to a new market research report "Consumer IAM Market ... Authorization), Service, Authentication Type, Deployment Mode, Vertical, and Region - Global Forecast ... from USD 14.30 Billion in 2017 to USD 31.75 Billion by 2022, ... ... MarketsandMarkets Logo ...
(Date:4/11/2017)... Research and Markets has announced the addition of the ... ... to grow at a CAGR of 30.37% during the period 2017-2021. ... been prepared based on an in-depth market analysis with inputs from ... prospects over the coming years. The report also includes a discussion ...
Breaking Biology News(10 mins):
(Date:8/11/2017)... ... August 11, 2017 , ... Algenist continues to disrupt ... unlocking collagen like never before. , Collagen is the key structural element skin ... with Liquid Collagen™, which include: , First to market ...
(Date:8/10/2017)... ... August 09, 2017 , ... Teachers from three Philadelphia ... August 14th through the 16th, the University City Science Center will kick off ... 2016, provides Philadelphia-based middle school educators an opportunity for professional development related to ...
(Date:8/10/2017)... , ... August 09, 2017 , ... Okyanos Center for ... place at the Pelican Bay Hotel in Freeport, Grand Bahama on September 27, 2017. ... required. , With oversight from the Ministry of Health’s National Stem Cell Ethics ...
(Date:8/10/2017)... UK (PRWEB) , ... August 10, 2017 , ... ... announced an agreement establishing Kinokuniya Company Ltd. as its exclusive sales representative for ... exclusive sales representative for the SPIE Digital Library in Japan. , “We look ...
Breaking Biology Technology: