How gut bacteria change cancer drug activity

April 21, 2017
E. coli bacteria. Credit: NIH

The activity of cancer drugs changes depending on the types of microbes living in the gut, according to a UCL-led study into how nematode worms and their microbes process drugs and nutrients.

The discovery highlights the potential benefit of manipulating and diet to improve and the value of understanding why the effectiveness of drugs varies between individuals.

The study, published today in Cell and funded by Wellcome, the Royal Society and Medical Research Council, reports a new high-throughput screening method that unravels the complex relationship between a host organism, their gut and action.

"The efficacy of colorectal treatments varies greatly between patients. We wanted to know if this could be caused by microbes changing how the body processes the drugs. We've developed a rigorous system that could be used for pre-clinical screening of drug interactions in the context of host and microbe, or for designing bacteria for drug-delivery which could revolutionise treatments," explained study lead, Dr Filipe Cabreiro (UCL Biosciences).

"We forget that there are many organisms living in our bodies that interact with the food and drugs we ingest. Until now, probing the relationship between host, microbe and drug has proved difficult. Often microbes are studied in isolation, which isn't realistic, but using our in vivo method, we've had some striking insights into how drug activity can be bolstered or suppressed by ," said Dr Timothy Scott, first author (UCL Biosciences).

The team, involving researchers from UCL, the European Molecular Biology Laboratory (EMBL, Germany), University of Helsinki and Birkbeck, University of London, developed a new three-way screen based on C. elegans. This worm is commonly used as a simple model for human metabolism due to its evolutionary similarity to humans and its comparable relationship with microbes.

They screened 55,000 conditions in C. elegans by varying bacterial genes as well as drug types and doses. The team then used computational analysis to map in great detail how the bacteria's genetics, dietary sources and chemical compounds affected the effectiveness of fluoropyrimidines, a common type of colorectal cancer drug.

Fluoropyrimidines act by stopping DNA being produced, which prevents cells from dividing in an uncontrolled fashion, a typical feature of cancer cells. They are commonly given in a pro-drug form, meaning that it needs to be broken down by the liver to become an active drug. Although fluoropyrimidines are a common cancer treatment, there is no universally accepted dose and genetics alone do not explain differences in patient responses to the drug.

The extensive screening in this study highlighted two distinct ways that bacteria change drug activity in worms. Firstly, some bacterial strains help to process the pro-drug into an active drug form, enhancing drug activity, and secondly, the bacteria influence the metabolic environment of the cell making it more prone to drug-induced cell death.

The team also found that co-therapies for cancer may limit treatment success if the host-microbe-drug interactions are not taken into account. For example, they found the anti-diabetic drug metformin reduces the efficacy of fluoropyrimidines in C. elegans by inhibiting the positive actions of bacteria.

"We've highlighted a critical missing component in our understanding of how drugs really work to treat disease. We plan on investigating this area further, as identifying which microbes are responsible for drug activity in humans, and their regulation by dietary supplements, could have a dramatic impact on cancer treatment outcome," Dr Cabreiro concluded.

Explore further: The connection between chemotherapy and infection

More information: Timothy A. Scott et al. Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy inC. elegans, Cell (2017). DOI: 10.1016/j.cell.2017.03.040

Related Stories

The connection between chemotherapy and infection

November 16, 2016
Most people's ideas of bacteria and fungi tend to be negative, since we often think of them only as the cause of many human diseases. Yet we must not forget that the average human body is colonized by trillions of microbes ...

Study reveals how diabetes drug delays ageing in worms

March 28, 2013
A widely prescribed type 2 diabetes drug slows down the ageing process by mimicking the effects of dieting, according to a study published today using worms to investigate how the drug works.

Research on new, rapid screening test identifies potential therapies against drug-resistant bacteria

November 10, 2016
Researchers at the National Institutes of Health's National Center for Advancing Translational Sciences (NCATS), Clinical Center and National Institute of Allergy and Infectious Diseases (NIAID) have created a new way to ...

How gut microbes help chemotherapy drugs

October 4, 2016
Two bacterial species that inhabit the human gut activate immune cells to boost the effectiveness of a commonly prescribed anticancer drug, researchers report October 4 in Immunity. The study identifies a new role for Enterococcus ...

Treating cancer with drugs for diabetes and hypertension

December 27, 2016
A combination of a diabetes medication and an antihypertensive drug can effectively combat cancer cells. The team of researchers led by Prof. Michael Hall at the Biozentrum of the University of Basel has also reported that ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.