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:6/22/2016)... ANGELES , June 22, 2016 /PRNewswire/ ... identity management and verification solutions, has partnered ... edge software solutions for Visitor Management, Self-Service ... provides products that add functional enhancements ... partnership provides corporations and venues with an ...
(Date:6/16/2016)... 2016 The global ... reach USD 1.83 billion by 2024, according to ... Technological proliferation and increasing demand in commercial buildings, ... drive the market growth.      (Logo: ... development of advanced multimodal techniques for biometric authentication ...
(Date:6/7/2016)... , June 7, 2016  Syngrafii Inc. ... a business relationship that includes integrating Syngrafii,s patented ... branch project. This collaboration will result in greater ... the credit union, while maintaining existing document workflow ... http://photos.prnewswire.com/prnh/20160606/375871LOGO ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... 27, 2016 , ... Rolf K. Hoffmann, former senior vice ... University of North Carolina Kenan-Flagler Business School effective June 27. , ... with a focus on the school’s international efforts, leading classes and participating in ...
(Date:6/24/2016)... 2016 Epic Sciences unveiled a liquid ... to PARP inhibitors by targeting homologous recombination deficiency ... new test has already been incorporated into numerous ... types. Over 230 clinical trials are ... including PARP, ATM, ATR, DNA-PK and WEE-1. Drugs ...
(Date:6/23/2016)... ... 23, 2016 , ... UAS LifeSciences, one of the leading ... UP4™ Probiotics, into Target stores nationwide. The company, which has been manufacturing high ... its list of well-respected retailers. This list includes such fine stores as Whole ...
(Date:6/23/2016)... 23, 2016 Houston Methodist Willowbrook Hospital ... Sports Association to serve as their official health ... Methodist Willowbrook will provide sponsorship support, athletic training ... association coaches, volunteers, athletes and families. ... Sports Association and to bring Houston Methodist quality ...
Breaking Biology Technology: