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Clinical Laboratories and Pathology Groups

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UCSD Scientists Discover a Person’s Skin Microbiome May Make Some Individuals More Attractive to Biting Insects than Others

Research could lead to clinical laboratory tests in service of precision medicine therapies to reduce a person’s susceptibility to being targeted by blood-sucking insects

Ever wonder why some people attract mosquitoes while others do not? Could biting insects pick their victims by smell? Scientists in California believe the answers to these questions could lead to new precision medicine therapies and clinical laboratory tests.

The research revealed evidence that some blood-sucking insects may identify their prey by homing in on the “scent” of chemicals produced by bacteria located in the skin microbiome of animals and humans.  

This is yet another example of research into one area of the human microbiome that might someday lead to a new clinical laboratory test, in this case to determine if a person is more likely to attracts biting insects. If there were such a test, precision medicine therapies could be developed that change an individual’s microbiome to discourage insects from biting that individual.

Then, the clinical laboratory test would have value because it helped diagnose a health condition that is treatable.

Researchers from the University of California San Diego (UCSD) School of Medicine, Department of Pediatrics, and Scripps Institution of Oceanography examined blood-sucking flies that are attracted to bats to learn how the insects choose which bats to feed on. One of the authors of the study, Holly Lutz, PhD, had previously encountered multitudes of bats while performing malaria research in bat caves in Kenya and Uganda.

Lutz is an Assistant Project Scientist, Department of Pediatrics, in the Center for Microbiome Innovation at the UCSD School of Medicine. She is also a Scientific Affiliate at the Field Museum of Natural History.

The researchers published their findings in the scientific journal Molecular Ecology, titled, “Associations Between Afrotropical Bats, Eukaryotic Parasites, and Microbial Symbionts.”

Holly Lutz, PhD

Curiosity regarding why mosquitoes seem to gravitate towards some humans over others was the original catalyst for the UCSD Medical School research. “You know when you go to a barbeque and your friend is getting bombarded by mosquitos, but you’re fine? There is some research to support the idea that the difference in mosquito attraction is linked to your skin microbiome—the unique community of bacteria living on your skin,” said Holly Lutz, PhD (above), first author of the UCSD study. “Keeping in mind that some people are more attractive to mosquitoes than others, I wondered what makes insects attracted to some bats but not others.” Lutz’s research could lead to clinical laboratory tests that drive precision medicine therapies to alter human skin microbiomes and make people less attractive to biting insects. (Photo copyright: The Field Museum of Natural History.)

Biting Flies Prefer Specific Bats

“In these caves, I’d see all these different bat species or even taxonomic families roosting side by side. Some of them were loaded with bat flies, while others had none or only a few,” Lutz said in Phys.org. “And these flies are typically very specific to different kinds of bats—you won’t find a fly that normally feeds on horseshoe bats crawling around on a fruit bat. I started wondering why the flies are so particular. Clearly, they can crawl over from one kind of bat to another, but they don’t really seem to be doing that.”

The researchers suspected that the bacteria contained in the skin microbiomes of individual bats could be influencing which bats the flies selected to bite. The bacteria produce a distinctive odor which may make certain bats more attractive to the flies.

The type of fly assessed for the study are related to mosquitoes and most of them are incapable of flight.

“They have incredibly reduced wings in many cases and can’t actually fly,” Lutz explained. “And they have reduced eyesight, so they probably aren’t really operating by vision. So, some other sensory mechanisms must be at play, maybe a sense of smell or an ability to detect chemical cues.”

To test their hypothesis, the research team collected skin and fur samples from the bodies and wings of a variety of bat species located in various caves around Kenya and Uganda. They collected their samples at 14 field sites from August to October in 2016. They then examined the DNA of the bats as well as the microbes residing on the animals’ skin and searched for the presence of flies.

“The flies are exquisitely evolved to stay on their bat,” said Carl Dick, PhD, a professor of biology at Western Kentucky University and one of the study’s authors. “They have special combs, spines, and claws that hold them in place in the fur, and they can run quickly in any direction to evade the biting and scratching of the bats, or the efforts by researchers to capture them,” he told Phys.org.

“You brush the bats’ fur with your forceps, and it’s like you’re chasing the fastest little spider,” Lutz said. “The flies can disappear in a split second. They are fascinatingly creepy.”

Genetic Sequencing DNA of Bat Skin Bacteria

After collecting their specimens, the researchers extracted DNA from the collected bacteria and performed genetic sequencing on the samples. They created libraries of the bacteria contained in each skin sample and used bioinformatics methods to identify the bacteria and compare the samples from bats that had flies versus those that did not.

“How the flies actually locate and find their bats has previously been something of a mystery,” Dick noted. “But because most bat flies live and feed on only one bat species, it’s clear that they somehow find the right host.”

The scientists discovered that different bat families did have their own distinctive skin microbiome, even among samples collected from different locations. They found that differences in the skin microbiomes of certain bats does contribute to whether those bats have parasites. But not all their questions were answered.

“We weren’t able to collect the actual chemicals producing cue—secondary metabolites or volatile organic compounds—during this initial work. Without that information, we can’t definitively say that the bacteria are leading the flies to their hosts,” Lutz said.

Next Steps

“So, next steps will be to sample bats in a way that we can actually tie these compounds to the bacteria. In science, there is always a next step,” she added.

This research illustrates that there may be a reason why certain animals and humans tend to be more attractive to insects than others. It is also possible that an individual’s skin microbiome may explain why some people are more prone to mosquito and other types of insect bites.

More research and clinical studies on this topic are needed, but it could possibly lead to a clinical laboratory test to determine if an individual’s skin microbiome could contribute to his or her potential to being bitten by insects. Such a test would be quite beneficial, as insects can carry a variety of diseases that are harmful to humans.

Perhaps a precision medicine therapy could be developed to alter a person’s microbiome to make them invisible to blood-sucking insects. That would be a boon to regions of the world were diseases like malaria are spread by insect bites.

—JP Schlingman

Related Information:

Blood-sucking Flies May Be Following Chemicals Produced by Skin Bacteria to Locate Bats to Feed on

Associations Between Afrotropical Bats, Eukaryotic Parasites, and Microbial Symbionts

The Human Skin Microbiome

Polygenic Scores Show Potential to Predict Humans’ Susceptibility to a Range of Chronic Diseases; New Clinical Laboratory Genetic Tests Could Result from Latest Research

Access to vast banks of genomic data is powering a new wave of assessments and predictions that could offer a glimpse at how genetic variation might impact everything from Alzheimer’s Disease risk to IQ scores

Anatomic pathology groups and clinical laboratories have become accustomed to performing genetic tests for diagnosing specific chronic diseases in humans. Thanks to significantly lower costs over just a few years ago, whole-genome sequencing and genetic DNA testing are on the path to becoming almost commonplace in America. BRCA 1 and BRCA 2 breast cancer gene screenings are examples of specific genetic testing for specific diseases.

However, a much broader type of testing—called polygenic scoring—has been used to identify certain hereditary traits in animals and plants for years. Also known as a genetic-risk score or a genome-wide score, polygenic scoring is based on thousands of genes, rather than just one.

Now, researchers in Cambridge, Mass., are looking into whether it can be used in humans to predict a person’s predisposition to a range of chronic diseases. This is yet another example of how relatively inexpensive genetic tests are producing data that can be used to identify and predict how individuals get different diseases.

Assessing Heart Disease Risk through Genome-Wide Analysis

Sekar Kathiresan, MD, Co-Director of the Medical and Population Genetics program at Broad Institute of MIT/Harvard and Director of the Center for Genomics Medicine at Massachusetts General Hospital (Mass General); and Amit Khera, MD, Cardiology Fellow at Mass General, told MIT Technology Review “the new scores can now identify as much risk for disease as the rare genetic flaws that have preoccupied physicians until now.”

“Where I see this going is that, at a young age, you’ll basically get a report card,” Khera noted. “And it will say for these 10 diseases, here’s your score. You are in the 90th percentile for heart disease, 50th for breast cancer, and the lowest 10% for diabetes.”

However, as the MIT Technology Review article points out, predictive genetic testing, such as that under development by Khera and Kathiresan, can be performed at any age.

“If you line up a bunch of 18-year-olds, none of them have high cholesterol, none of them have diabetes. It’s a zero in all the columns, and you can’t stratify them by who is most at risk,” Khera noted. “But with a $100 test we can get stratification [at the age of 18] at least as good as when someone is 50, and for a lot of diseases.”

Sekar Kathiresan, MD (left), Co-Director of the Medical and Population Genetics program at Broad Institute at MIT/Harvard and Director of the Center for Genomics Medicine at Massachusetts General Hospital; and Amit Khera, MD (right), Cardiology Fellow at Mass General, are researching ways polygenic scores can be used to predict the chance a patient will be prone to develop specific chronic diseases. Anatomic pathology biomarkers and new clinical laboratory performed genetic tests will likely follow if their research is successful. (Photo copyrights: Twitter.)

Polygenic Scores Show Promise for Cancer Risk Assessment

Khera and Kathiresan are not alone in exploring the potential of polygenic scores. Researchers at the University of Michigan’s School of Public Health looked at the association between polygenic scores and more than 28,000 genotyped patients in predicting squamous cell carcinoma.

“Looking at the data, it was surprising to me how logical the secondary diagnosis associations with the risk score were,” Bhramar Mukherjee, PhD, John D. Kalbfleisch Collegiate Professor of Biostatistics, and Professor of Epidemiology at U-M’s School of Public Health, stated in a press release following the publication of the U-M study, “Association of Polygenic Risk Scores for Multiple Cancers in a Phenome-wide Study: Results from The Michigan Genomics Initiative.”

“It was also striking how results from population-based studies were reproduced using data from electronic health records, a database not ideally designed for specific research questions and [which] is certainly not a population-based sample,” she continued.

Additionally, researchers at the University of California San Diego School of Medicine (UCSD) recently published findings in Molecular Psychiatry on their use of polygenic scores to assess the risk of mild cognitive impairment and Alzheimer’s disease.

The UCSD study highlights one of the unique benefits of polygenic scores. A person’s DNA is established in utero. However, predicting predisposition to specific chronic diseases prior to the onset of symptoms has been a major challenge to developing diagnostics and treatments. Should polygenic risk scores prove accurate, they could provide physicians with a list of their patients’ health risks well in advance, providing greater opportunity for early intervention.

Future Applications of Polygenic Risk Scores

In the January issue of the British Medical Journal (BMJ), researchers from UCSD outlined their development of a polygenic assessment tool to predict the age-of-onset of aggressive prostate cancer. As Dark Daily recently reported, for the first time in the UK, prostate cancer has surpassed breast cancer in numbers of deaths annually and nearly 40% of prostate cancer diagnoses occur in stages three and four. (See, “UK Study Finds Late Diagnosis of Prostate Cancer a Worrisome Trend for UK’s National Health Service,” May 23, 2018.)

An alternative to PSA-based testing, and the ability to differentiate aggressive and non-aggressive prostate cancer types, could improve outcomes and provide healthcare systems with better treatment options to reverse these trends.

While the value of polygenic scores should increase as algorithms and results are honed and verified, they also will most likely add to concerns raised about the impact genetic test results are having on patients, physicians, and genetic counselors.

And, as the genetic testing technology of personalized medicine matures, clinical laboratories will increasingly be required to protect and distribute much of the protected health information (PHI) they generate.

Nevertheless, when the data produced is analyzed and combined with other information—such as anatomic pathology testing results, personal/family health histories, and population health data—polygenic scores could isolate new biomarkers for research and offer big-picture insights into the causes of and potential treatments for a broad spectrum of chronic diseases.

—Jon Stone

Related Information:

Forecasts of Genetic Fate Just Got a Lot More Accurate

Polygenic Scores to Classify Cancer Risk

Association of Polygenic Risk Scores for Multiple Cancers in a Phenome-Wide Study: Results from the Michigan Genomics Initiative

Polygenic Risk Score May Identify Alzheimer’s Risk in Younger Populations

Use of an Alzheimer’s Disease Polygenic Risk Score to Identify Mild Cognitive Impairment in Adults in Their 50s

New Polygenic Hazard Score Predicts When Men Develop Prostate Cancer

Polygenic Hazard Score to Guide Screening for Aggressive Prostate Cancer: Development and Validation in Large Scale Cohorts

UK Study Finds Late Diagnosis of Prostate Cancer a Worrisome Trend for UK’s National Health Service

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