Navigation Links
Bacterial blockade

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
Harvard University

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:
(Date:11/12/2015)... 2015  Arxspan has entered into an agreement ... for use of its ArxLab cloud-based suite of ... partnership will support the institute,s efforts to electronically ... information internally and with external collaborators. The ArxLab ... the Institute,s electronic laboratory notebook, compound and assay ...
(Date:11/11/2015)... --  MedNet Solutions , an innovative SaaS-based eClinical technology company ... to announce that it will be a Sponsor of the ... be held November 17-19 in Hamburg , ... iMedNet , MedNet,s easy-to-use, proven and affordable ... been able to deliver time and cost savings of up ...
(Date:11/10/2015)... 2015 About signature verification ... to identify and verify the identity of an ... the secure and accurate method of authentication and ... individual because each individual,s signature is highly unique. ... dynamic signature of an individual is compared and ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... 2015 The Global Genomics ... professional and in-depth study on the current state ... ) , The report ... definitions, classifications, applications and industry chain structure. The ... markets including development trends, competitive landscape analysis, and ...
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf ... the 2016 USGA Green Section Award. Presented annually since 1961, the USGA Green Section ... her work with turfgrass. , Clarke, of Iselin, N.J., is an extension ...
(Date:11/24/2015)... , Nov. 24, 2015 /CNW/ - iCo Therapeutics ("iCo" ... reported financial results for the quarter ended September ... in Canadian dollars and presented under International Financial ... States ," said Andrew Rae , ... regarding iCo-008 are not only value enriching for ...
(Date:11/24/2015)... /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS) (TSX: AEZ) (the ... the Toronto Stock Exchange, confirms that as of the ... developments that would cause the recent movements in the ... --> About Aeterna Zentaris Inc. ... Aeterna Zentaris is a specialty biopharmaceutical company engaged in ...
Breaking Biology Technology: