March 18, 2019

Powerful research tool uncovers link between gut microbiota and copper

Research team involves collaboration between Faculty of Science and Cumming School of Medicine

Author

Doug Ferguson, for the Faculty of Science

Antibiotics were used to deplete as much of the normal gut bacteria as possible in the small and large intestines of animals, and strong evidence was found that interactions between microbes and the host regulate the entry of copper into the cells of the large intestine. Members of the research team, from left: Keith Sharkey, Fernando Vicentini, Mike Weiser,Keri Miller, Simon Hirota.

From left: Keith Sharkey, Fernando Vicentini, Mike Weiser,Keri Miller, Simon Hirota.

Riley Brandt, University of Calgary

Scientists at the University of Calgary have found that the gut microbiota can change how animals metabolize copper, a trace nutrient vital to everything from normal development to cell function, as well as many metabolic processes.

Further research is needed to determine if the gut microbiota is similarly involved in people, says Dr. Kerri Miller, PhD, postdoctoral fellow in the Department of Physics and AstronomyFaculty of Science. Composed of bacteria and other microorganisms such as fungi and viruses, the gut microbiota has been proven to be fundamental to human health.

As they continue their research, scientists have potentially gained a powerful new way to explore the complex interactions between the body and the communities of bacteria, or microbiome, that are naturally present in the intestine, says Miller.

Strong evidence found                                                        

As detailed in a paper published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), antibiotics were used to deplete as much of the normal gut bacteria as possible in the small and large intestines of animals.

Strong evidence was found that interactions between microbes and the host regulate the entry of copper into the cells of the large intestine, says Miller, who is the study’s lead author. The study was a joint effort between researchers at the Faculty of Science and the Cumming School of Medicine (CSM).

Disturbances in the processing of copper by the body have been linked to diseases ranging from Alzheimer’s and Parkinson’s to rheumatoid arthritis, cardiovascular disease, inflammatory bowel disease, and cancer. The metal is naturally present in the environment in the form of two stable isotopes, Cu 63 and 65.

Miller examined the isotopes by using an inductively coupled plasma mass spectrometer. Such devices were originally used to study things such as ore samples in geology.

Collaboration was 'breakthrough' 

“I think that for Kerri to have the imagination to apply this tool to a biological investigation is really critical,” says senior author and supervisor Dr. Mike Wieser, PhD, an associate professor in the Department of Physics and Astronomy.

“This method can provide information that no other technique can, because it can follow the stable isotopes through specific reactions. To collaborate with the CSM was a real breakthrough because we are hopefully introducing a new way of looking at these interactions in living systems, an approach that is not commonly used in medicine at the moment.”

Although copper is an important micronutrient in the body, “it is also potentially toxic to cells, so the body tightly regulates it,” says Miller. “You can easily detect any small changes in metabolic activity through changes in the stable isotopic composition.”

The isotopes are a normal part of things such as food and water. “Kerri did not introduce radioactive tracers to the samples, or expose the animal models to isotopes of copper that are not usually present in their diet or environment,” says Wieser.

“This is why it is such a powerful technique, because you can essentially look at what is there naturally and how processes are affecting the relative numbers of the different isotopes in the system. There is enormous potential here to apply this tool to some of the copper processes that have implications for neurological and other diseases, and maybe understand the mechanisms in a new way that we couldn’t previously.”

“Kerri and Mike led us to embark on a wonderful collaboration” says co-senior author Dr. Keith Sharkey, PhD, professor in the departments of medicine and physiology and pharmacology, member of the Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, and the Crohn’s and Colitis Canada Chair in Inflammatory Bowel Disease Research at the CSM. “They wanted to follow stable isotopes from the diet into cells, and in doing so led us down a path of discovery to find that gut microbes play a key part in the process.”

Microbiota research at forefront 

Miller’s results were confirmed by analyses that showed changes in the levels of copper transporter proteins in the intestine, says the study’s co-lead author Fernando Vicentini, a PhD student co-supervised by Sharkey and Dr. Simon Hirota, PhD, associate professor in the departments of physiology and pharmacology, and microbiology, immunology and infectious diseases, member of the Snyder Institute, and the Dr. Lloyd Sutherland Investigator in IBD/GI Research.

There are many more bacterial cells inhabiting every human body than there are human cells, says Vicentini. “There is a lot of research focusing on microbiota now, and how the bugs in our gut are regulating our physiology, involving every aspect of our body,” he says.

“I would say it will take a long time for this basic science to translate to humans. Very few people have looked at microbiota and copper, so we are just at the beginning of this exciting journey.”

The study was jointly funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR), along with internal funding from the Crohn’s and Colitis Canada Chair in IBD Research and Dr. Lloyd Sutherland Investigatorship in IBD/GI Research in the CSM. Vicentini was supported by a CNPq graduate scholarship provided by the Brazilian government. Hirota holds a Canada Research Chair. Miller is supported by funds from the Department of Physics and Astronomy and Grand Challenges funding through the Faculty of Science.