Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.

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2 days ago · Testing the bugs within to maintain health, detect and treat disease

Article by Sharon Rosen

Purna Kashyap, M.B.B.S.

The use of microbiome testing – which analyzes the trillions of bacteria in and on the body – is on the move. It’s going from the research lab into the clinic to help guide patient care. DNA testing technologies have revolutionized researchers’ ability to identify individual bacterial strains driving disease. Now genomic testing is helping diagnose the source of infections, develop personalized diets, find new treatments for functional and inflammatory conditions of the gut and identify new screening tools for certain cancers.

For Purna Kashyap, M.B.B.S., this is just the beginning. As the Bernard and Edith Waterman co-director for the Mayo Clinic Center for Individualized Medicine Microbiome Program, Dr. Kashyap envisions the coming years as a pivotal time for moving the latest discoveries from the lab to new diagnostic tests and individualized microbiome-based therapies for patients.

“Just as genomics plays a key role in personalized medicine, the microbiome also affects our individual health – boosting our immune system, helping us digest food and influencing how we respond to medications. We are each born and live with a unique microbiome. But unlike our genes, the microbiome can be manipulated and changed. That’s why physicians need to consider the role of the microbiome, along with genetics and other factors, especially when treating patients with complex diseases like autoimmune disorders, gastrointestinal diseases, diabetes, obesity and many types of cancer,” says Dr. Kashyap.

Technologies developed in the lab provide answers in the clinic

A high fever, increased blood pressure and rapid heart rate – these are all symptoms that could be caused by an infection. But for some patients, traditional blood tests fail to identify the source of the illness. That’s where microbiome testing technologies developed in the laboratory are already helping to find answers for Mayo Clinic patients. Within a day and in some cases just hours, the testing is revealing the source of a previously undiagnosed infection, allowing for treatment with targeted therapies.

“We can now identify the specific bacteria causing serious infections even though we are not able to culture them” says Dr. Kashyap.

Test results can help physicians choose targeted therapies to treat infections and avoid the use of “dynamite” antibiotics explains Dr. Kashyap.

“Genomic testing allows us to select specific therapies to kill only the bacteria causing the infection, rather than prescribing an antibiotic that eliminates all of the gut bacteria, leaving the patient susceptible to other illnesses,” says Dr. Kashyap.

Next steps – identifying biomarkers to predict, diagnose and treat disease

To expand the use of microbiome testing, Dr. Kashyap and his colleagues are collaborating with the Center’s Clinomics Program to integrate microbiome testing into patient care as well as clinical trials. Their goal is to identify microbiome biomarkers that could be used to develop screening tests to detect early signs of disease or new individualized therapies, tailored to a person’s microbiome.

Going forward, microbiome testing may also provide important information about disease risk for healthy patients.

“This testing could provide healthy patients with information about disease risk and help define steps they can take to manage their health,” says Dr. Kashyap.

Eat this, not that – personalized diets

Dr. Kashyap and his colleagues have recently tested a model that successfully predicted changes in blood glucose (sugar) levels based on an individual’s age, lifestyle habits and microbiome.

“With the model, we can manage blood sugar levels by changing diet to match the microbiome rather than trying to change the microbiome which may take time”” says Dr. Kashyap.

Dr. Kashyap and his team have also uncovered a link between a person’s microbiome and their ability to lose weight.

“In a pilot study, we found that after switching to a lower-calorie-diet rich in fruit and vegetables, some people were able to lose weight more easily than others due to the type of bacteria in their gut.”

Learn more about the team’s research here.

Matching research to patient needs – a focus on gut health

Throughout his career as a gastroenterologist, Dr. Kashyap has focused on conducting research to meet the needs of his patients.

He has explored how gut bacteria control normal gut function and contribute to the development of gastrointestinal disorders, such as irritable bowel syndrome.

In addition, he has investigated how bacteria lead to opportunistic infections that can become life threatening, such as c. difficile, which can occur after a patient has had a prolonged stay in a hospital or nursing facility. The Mayo team has used new treatment approaches, including fecal transplants, to restore these patients’ gut microbiome with healthy bacteria.

“Some patients have a microbiome composition that makes them more susceptible to c. difficile infection. We are working on strategies to prevent the infection as well as develop a treatment with a bacteria-containing pill.”

For Dr. Kashyap, these research efforts are just the tip of the iceberg. “As we learn more, we’ll be able to offer patients better screening and treatment for a wide range of diseases, tailored to their unique needs.”

Pushing the envelope to uncover causes, new treatments for colorectal cancer

Read the related article, highlighting Microbiome Program co-director Nicholas Chia, Ph.D., and his research to uncover early signs of colorectal cancer to improve screening and treatment for the disease.

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This article originally appeared on the Individualized Medicine blog on April 2, 2019

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Wed, Apr 10 6:00am · Genetic testing reveals risk, steps to prevent aortic dissection

Article by Sharon Rosen

Stephanie Van Doren and her family

Stephanie Van Doren never realized that taking 30 mile bike rides in the Florida heat was putting her life at risk. But, care for digestive problems also uncovered that she was at risk for an aortic dissection, a potentially fatal condition that could occur with intense exercise. Her care team at Mayo Clinic’s campus in Florida quickly connected the dots. Her family history and physical exam painted a picture that pointed to a hereditary condition. They recommended genetic testing and the results provided lifesaving information to Van Doren and her family.

Unraveling a medical mystery through genetic testing

Sarah Macklin

Van Doren met with Sarah Macklin, a genetic counselor in the Department of Clinical Genomics and Center for Individualized Medicine.

During the first appointment, Macklin mapped Van Doren’s family medical history for three generations. They also discussed the benefits, risks, and limitations of testing, and what steps could be taken if any of the tests came back positive.

Van Doren had testing to explore two questions: did she have any identifiable genetic risk factors that significantly increased her risk of having a thoracic aortic aneurysm and aortic dissection? Did she have any identifiable genetic risk factors that significantly increased her risk for breast cancer since her sister had died from the disease at a young age?

Results showed that she did have the genetic risk factor for aortic dissection, but did not have a genetic risk identified for breast cancer.

“I was devastated that I was at increased risk for aortic dissection. This runs deep in my family and I had seen firsthand how it has affected my relatives,” she says.

Many members of Van Doren’s family had an aortic dissection at a young age. The condition can be life threatening and occurs when the inner layers of the aorta, the large blood vessel branching off the heart, tear.

As a result, she and her family decided that her children should also have genetic testing. They met with Macklin to learn more about the process and implications.

“This second conversation is much different than the first,” explains Macklin. “We now are looking for a particular genetic variant that has been identified in a parent or other family member. We take time to explain to children – in terms that they can understand – what we are looking for, why we are looking for it and what it will mean if the test comes back positive.”

“It’s very important to be honest with children so they can understand and agree to have the testing, even if they are not old enough to give the consent themselves.”

Two of Van Doren’s three children have the gene variant linked to aortic dissection. She received these results first and then shared them with her children.

“It was important for me to have time to process the results myself and then explain them to my children,” she says.

Macklin also shared the genetic test results with Mayo specialists in Cardiovascular Medicine who are providing Van Doren e and her children with the monitoring and follow up care they need to stay healthy.

“Never did I imagine that I would have genetic testing, but thankfully I did – the results probably saved my life and will help my children live a healthier life.” she says. “It’s difficult to learn that you are at risk for such a serious condition. But now we have the information we need to be proactive and stay healthy.”

Know and share your family medical history with your health care team 

Timothy Woodward, M.D.

Van Doren first came to Mayo seeking relief from digestive problems. It was her gastroenterologist, Timothy Woodward, M.D., who first recognized that her family history plus characteristics he observed during her physical exam pointed to the possibility that she had a hereditary condition.

“Ms. Van Doren did what we hope all patients will do – know and share their family medical history with their physicians,” says Dr. Woodward. “This information plus a complete clinical evaluation allows us to provide patients with individualized care, tailored to their needs.”

Moving forward – living life to the fullest

“I have always led a very active lifestyle – enjoying skydiving and leading group fitness classes. Now I am unable to do these things. I can exercise, but I need to pay close attention to my heart rate and avoid intense exertion. My children can still do many of the activities they love and will continue to be monitored as they grow,” Van Doren explains.

Looking back, she reflects that there were definitely highs and lows during the genetic testing process. Thanks to the coordinated efforts of her Mayo Clinic care team, she and her family found the answers they needed.

“We have moved on – each day is filled with activities for 3 busy children – we’re living life to the fullest.”

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This article originally appeared on the Individualized Medicine blog on March 26, 2019

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Learn from and network with researchers and innovators in oncology at

Individualizing Medicine 2019 Conference: Precision Cancer Care through Immunotherapy and Genomics

Key themes include:

  • CAR-T therapy
  • Clonality
  • Pharmacogenomics
  • Lineage Plasticity
  • National Cancer Institute.

Join the conversation

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Thu, Mar 21 6:00am · Colon cancer: a new era in cancer screening and detection

Image of DNA with "family" written in itMarch is Colorectal Cancer Awareness Month, a time to focus on one of the most common and preventable forms of cancer. Mayo Clinic is applying a new genomic lens to colorectal and other cancers to identify which are the types that run in families. The answer to that could open new treatment options and also take the guess work out of who else in your family is at higher risk for cancer.

Niloy “Jewel” Samadder, M.D., a gastroenterologist at Mayo Clinic’s Arizona campus, is leading efforts to usher in a new era of screening and detection that focuses on identifying hereditary cancers. Research shows that 1 in every 15 cases of colon cancer and possibly up to 1 in every 5 cases of cancer overall are linked to underlying inherited genetic mutations.

A diagnosis of hereditary cancer often changes treatment to an individualized approach shaped by a patient’s genetic makeup. Mayo Clinic, with the support of the Center for Individualized Medicine, is moving toward testing all cancer patients for such inherited mutations — not just patients with cancer in their family tree.

photo of Dr. Niloy "Jewel Samadder

Niloy “Jewel” Samadder

“If we know that cancer was genetically predisposed, it can lead to unique options ensuring that treatments target the cancer and minimize side effects,” says Dr. Samadder. “For example, research shows that certain targeted chemotherapies and immunotherapies are not specific to the type of tumor or cancer but really act on certain molecular pathways. So, whether that cancer is colon, prostate or breast, we can respond with a drug that is targeted to the genetic mutations that caused that cancer rather than a specific tumor.”

To identify hereditary cancer, Mayo uses a robust DNA blood test panel that examines genes known to have links to cancer.

“This is the most comprehensive cancer genetic panel available today,” says Dr. Samadder. “We believe this gives us the tools for catching and treating inherited cancers that might have gone undetected in the past.”

If this test finds you have an inherited cancer, there is a 50 percent chance your immediate family members have the same genetic alteration that would increase their chance of developing a similar cancer. Under current cancer screening guidelines, up to half of all inherited cancers go undetected — a missed opportunity for early detection and possibly even cancer prevention.

Those with a genetic predisposition face a greater than average lifetime risk for cancer, but it is not 100 percent certain they would develop the disease. Lifestyle and environment also play a role in cancer risk.

Prevent a second cancer

Keila Alvarado of Phoenix was diagnosed with rectal cancer in 2008 at the age of 32. Genetic testing revealed Lynch syndrome, a hereditary condition that puts her at higher risk of developing colon, ovarian, uterine, stomach and other cancers.

Photo of Keila Alvarado

Keila Alvarado

“I was surprised. I really didn’t understand much about genetics at the time. I’m happy to have this information, because it’s better to be prepared. I now understand my risk for future cancers,” says Alvarado.

With grit and determination, Ms. Alvarado fought rectal cancer with surgery, chemotherapy and radiation. Now in remission, she has turned her attention to a new challenge: preventing a second type of cancer related to Lynch syndrome. She’s had a pre-emptive hysterectomy, has yearly blood work and screenings and is vigilant about her health.

“Any time the doctor says this is a preventive measure, I’m like, ‘ya, let’s do it.’ I don’t mind the different tests. I also take seriously my intake of food and how I can eat healthier. I try to be conscious of what I do and live a healthy lifestyle,” she says.

Now others in Alvarado’s family know they, too, could be at risk of inherited mutations that put them at higher risk for cancer. Some family members have chosen to have genetic testing, and those who also tested positive for Lynch syndrome can take a proactive approach to prevention.

“For patients with Lynch Syndrome, we suggest earlier and more frequent screenings. We recommend the first colonoscopy at age 20 and then once every one to two years after that. That’s different from the normal population where we start at age 50 and test every five to 10 years after that. We also recommend more frequent imaging, blood work, urine tests and skin exams,” Dr. Samadder says. “We would also refer females to a gynecologist to monitor for risks of uterine and ovarian cancer — possibly even recommending pre-emptive surgery.”

In some cases, Mayo will refer patients for chromoendoscopy, an ultra-sensitive screening which applies a special stain during a colonoscopy to detect polyps that might have otherwise been missed.

Dr. Samadder says Keila Alvarado’s case is a great example of how a new era of genetic screening can help inform family members who might not have known they are at higher risk of cancer. They can respond proactively to try to prevent cancer or catch it an early stage when it is curable.

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This article was taken from the March 12, 2019 post on the Individualized Medicine blog.

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Learn from and network with researchers and innovators in oncology at

Individualizing Medicine 2019 Conference: Precision Cancer Care through Immunotherapy and Genomics

Westin Kierland Resort & Spa
Scottsdale, Arizona
Sept. 20-21, 2019

Join the conversation

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Wed, Mar 13 6:00am · Business innovation with an eye on improving vision

Destination Medical Center – One Discovery Square

If eyes are the window to the world, Timothy W. Olsen, M.D. is building high performance window frames. With a passion for restoring vision, the ophthalmologist set sights on developing and bringing to market a first-of-its-kind device for treating age-related macular degeneration. The synergies around the Destination Medical Center economic initiative and Mayo Clinic’s research and practice community prompted him to move his business and clinical/surgical practice from Atlanta to Rochester, Minnesota.

Timothy W. Olsen, M.D.

“The business environment is second to none. Mayo has made a statement through Destination Medical Center that it wants to be an innovation center for medical technology,” says Dr. Olsen. “That combination of business, technology and connection to Medical Alley bio businesses in Minnesota makes this is a really good place to develop and commercialize medical devices.”

Destination Medical Center is a 20-year, multibillion dollar public-private partnership to position Rochester as a global destination for health care, biotechnology and life science discoveries. The money supports public infrastructure and does not go to Mayo Clinic. The convergence of entrepreneurship, medical expertise and regulatory support, Dr. Olsen says, is the perfect place for a successful product launch.

“Destination Medical Center is the city of Rochester, Olmsted County and the state of Minnesota. With those components, hopefully there will be private sector support as well as the opportunity for engaging with people involved in funding early stage start-up companies, including venture capital funding opportunities,” says Dr. Olsen.

A new device for age-related macular degeneration

Macular degeneration affects more than 3 million Americans and is the leading cause of vision loss for people over 50. There is no cure or treatment in the early stages. Patients with end stage macular degeneration may be suitable for monthly eye injections, but that is expensive and inconvenient. The disease process usually progresses despite the injections.

That’s where Dr. Olsen’s business comes in. His team is advancing research on a surgically-implantable device, using a technology that was first conceived at the University of Minnesota and patented through Emory University. That device acts as a window or picture frame holding regenerative tissue in place to support the macula at the back of the eye, potentially reversing vision loss and preserving the function of the macula.

The National Institutes of Health/National Eye Institute awarded a Small Business Technology Transfer Research grant for a one-year, phase I feasibility study. The grant goes directly to Dr. Olsen’s company, located in the Mayo Clinic Business Accelerator, with sub grant funding for preclinical research at Mayo.

“The goal of this research grant is to support scientists launching commercialization of a product rather than the researcher studying technology from an outside company, in an effort to speed the movement of a product from the research lab into the marketplace,” says Dr. Olsen.

After the feasibility study, there is a possibility of additional early-stage funding through a larger two-year, phase II National Institutes of Health research grant. Once that is completed, access to private capital would likely be needed to continue product development. Dr. Olsen believes the entrepreneurial environment created through the Destination Medical Center initiative will help attract that private investment. If the device passes regulatory approvals, it may take five to 10 years before it is offered in a clinical setting to address the unmet needs of millions of people suffering from age-related macular degeneration.

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Thu, Mar 7 6:00am · What do Yellowstone rocks teach us about kidney stones

This article originally appeared on the Center for Individualized Medicine blog.

Mayo Clinic researchers are turning to Yellowstone National Park to unlock the secrets of kidney stones. Medical science long has been mystified by a cause and cure for this painful condition that affects more than 1 in 10 Americans. Mayo Clinic Center for Individualized Medicine and NASA Astrobiology Institute research finds kidney stones grow in dynamic ways that are similar to those observed in Mammoth Hot Springs rock formations at Yellowstone.

Nicholas Chia, Ph.D.

“For decades, we thought that kidney stones formed in a slow, steady, layer-by-layer process like dust settling in your house. However, new high-resolution cross sections of these stones indicate they repeatedly grow and dissolve on their way to becoming a fully formed stone. There are periods of rapid growth, large missing gaps and dissolution — it’s a back-and-forth process. This suggests that stones grow over time in a more complicated way than we previously knew, and that there may be new ways to prevent them,” says Nicholas Chia, Ph.D., co-director of the Mayo Clinic Center for Individualized Medicine Microbiome program. “We are very excited because we see the same types of patterns in kidney stones, Yellowstone rocks and many other environments on Earth.”

The kidney stone studies bring together geobiologists, microbiologists and nephrologists to prove their theory. The smoking gun, Dr. Chia says, would be a discovery that microbes — common bacteria — are driving kidney stone formation in the same way they do in Yellowstone hot spring deposits.

Kidney stone cross section

“We believe stone formation is microbially driven in the human body as well. We are trying to extract and genetically sequence the microbes and proteins that are present to figure out where they are in the stone and what processes they are responsible for,” says Dr. Chia. “We hope to answer this in future studies.”

Kidney stones are hard rocklike masses of mineral and acid salts often smaller than the head of a nail that lodge in the kidney and don’t dissolve. The only way to get rid of them is through painful urine passage or surgery.

The team is now working to understand how proteins and other biomolecules derived from both the kidney and the microbiome — the community of bacteria in your body — could lead to an eventual treatment. That’s especially important for people who follow medical advice and yet repeatedly suffer from kidney stones.

Yellowstone cross section

“If we understood the process of repeated crystallization and dissolution within kidney stones, we might be able to prescribe something that either dramatically slows the stone growth or significantly increases the disintegration. If we understood the diversity of microbes involved and their metabolic activity, we might be able to change the rates at which stones growth and dissolve, just as has been proven by research in Yellowstone hot springs. There are many options once we understand this process,” adds Dr. Chia.

Dr. Chia’s team has been working on these studies for approximately five years. He believes it will take a few more years of team science research to fully understand the combined role of the microbiome, renal (kidney) physiology and urine chemistry in growing and dissolving kidney stones.

Up to a half-million people a year visit the emergency room to seek relief from this condition, according to The National Kidney Foundation. Kidney stones are often associated with other disorders such as high blood pressure, diabetes and obesity.

Dr. Chia is the Bernard and Edith Waterman co-director of the Mayo Clinic Center for Individualized Medicine Microbiome Program.

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Thu, Feb 21 6:00am · Probiotics: One size does not fit all

This article originally appeared on the Center for Individualized Medicine blog

The allure of probiotics can be hard to resist. Popular belief holds that when you take probiotics in pill, powder or food, you boost your gut health with a powerful antidote to digestive diseases.

But what exactly are probiotics, and how do you separate truth from theory? What does the research say?

Purna Kashyap, M.B.B.S., a gastroenterologist and co-director of the Mayo Clinic Center for Individualized Medicine Microbiome program and a member of the scientific advisory board of American Gastroenterological Association (AGA)Gut Microbiome Center for Education and Research, explains what science reveals about probiotics.

Purna Kashyap, M.B.B.S.

“Probiotics are living microscopic organisms, most commonly bacteria or yeast. Probiotics are thought to improve overall health and have been tested in multiple disease states, but the majority of the studies are not on par with rigorous clinical trials done for drugs. As a result their effectiveness remains highly controversial, and it is unclear how they act,” says Dr. Kashyap.

In addition, probiotics are naturally present in many forms of fermented foods such as yogurt, kefir, sauerkraut, kimchi, miso and kombucha.

Commonly held beliefs about probiotics

1. Probiotics will work the same in everyone
Truth: all probiotics are not created equal, so may affect each individual and each health condition differently.

Dr. Kashyap points to recent studies in human and mice on how probiotics affect the gut. The first examined how they colonize the gut – in other words how they contribute to the good bacteria that supports good health. The second explored whether probiotics restore the gut bacteria after the use of antibiotics.

“What the studies found was quite surprising. They found that people may respond differently to the same probiotic based on their diet, genetics, microbiome, environment, and lifestyle and hence one size doesn’t fit all. Further, they found that probiotics may delay the recovery of gut bacteria following antibiotic use. While they did not measure clinical effects and only studied one probiotic made of 11 different bacteria, the findings did advance our understanding of probiotics,” adds Dr. Kashyap.

A goal of the Mayo Clinic Center for Individualized Medicine is to transform medical practice by taking an individualized approach that matches medical products and services to each person’s unique genetic profile.

2. Probiotics are safe

Truth: the majority of scientific studies on probiotics do not report harm, but that does not guarantee they are safe.

“The fact that no one is reporting harm is being construed that probiotics are safe. It is not the same thing. It just means the majority of studies have not done harm’s assessment, so we can’t say with certainty that they are safe or harmful, but they are generally considered to be safe. Further we don’t know the long term implications of probiotics, either,” Dr. Kashyap says.

“Individuals who have a chronic disease, are immunocompromised, or are elderly, should seek guidance from a medical provider on whether probiotics may be appropriate. In general, probiotics should not be taken without guidance from a medical provider.”

3. The benefit of probiotics can be measured by the combined findings from several small studies

Two large recent trials in nearly 1800 children found that commercial probiotic strains previously thought to benefit children with acute gastroenteritis were, in fact, not effective.

“Together these studies highlight the need for high quality clinical trials before we promote the use of specific probiotics in specific diseases,” says Dr. Kashyap.

“The biggest concern (about misinformation) is that people may be spending hundreds of dollars, because they have been led to believe that taking these probiotics will keep them heathy when in reality they may not make a difference, and we don’t know the long term consequences.”

What science has yet to prove about probiotics

All probiotics are not created equal, and their effects on a person’s health cannot be generalized.

“We believe probiotics may have an effect, but we don’t know specifically what that is. It is important to note that there is no U.S. Food and Drug Administration-approved use for probiotics. They are available on the market as food supplements, not as medical therapies,” says Dr. Kashyap. “Each person should discuss with a medical provider data that supports probiotic use.”

Despite lack of conclusive evidence, medical providers may recommend probiotics with the goals of:

  • acting as good bacteria in the gut.
  • providing health benefits such as boosting the immune system.
  • preventing harmful bacteria from growing in the gut.
  • producing useful by-products that improve our metabolism, our mood and the health of our colon.

To learn more ways to sift through fact or speculation, the AGA includes information on its website about probiotics and its position on recent research.

Dr. Kashyap is the Bernard and Edith Waterman co-director of the Mayo Clinic Center for Individualized Medicine Microbiome Program.

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Tue, Feb 12 6:00am · Mayo Clinic discovery advances potential individualized treatment for mesothelioma

Large chromosomal rearrangements present in mesothelioma could make it possible to understand which patients are likely respond to immunotherapy,  researchers at the Mayo Clinic Center for Individualized Medicine  have discovered. The research is published in the Journal of Thoracic Oncology.

Aaron Mansfield, M.D.

“What we’ve shown so far is that these large complex chromosomal rearrangements are frequent in mesothelioma and may provide a source of neoantigens (cancer proteins) that the immune system can recognize,” says Aaron Mansfield, M.D., a Mayo Clinic oncology researcher and lead author on the paper. “It would be an entirely new way of predicting response.”

This finding is significant in part because the prognosis is often poor for mesothelioma — a rare, aggressive form of cancer  linked to asbestos exposure that forms on tissue lining in the lungs, heart and abdomen. There is no cure, and standard cancer treatment of chemotherapy, radiation and surgery doesn’t work for everyone.

“Mesothelioma does not have many of the mutations that are common in other cancers. Instead, there were chromosomal rearrangements that may have prognostic and therapeutic implications,” says Dr. Mansfield. “There were many more rearrangements than we expected. We were able to identify complex patterns of rearrangements called chromothripsis and chromoplexy. The extent of these patterns has never before been described in mesothelioma.”

Many types of DNA changes are known to be present in cancer cells. Using advanced genomic technology, a research team at Mayo Clinic was able to zero in on precise genetic variants driving mesothelioma. They used a new technology known as mate-pair sequencing, which looks at chromosomal rearrangements.

George Vasmatzis, Ph.D.

“Mate pair sequencing is an inexpensive way to scan the whole genome of tumor cells for chromosomal abnormalities that could give rise to cancer–causing proteins. By detecting all these abnormal junctions, mate pair sequencing reveals a new biological marker for predicting response to immunotherapy,” says George Vasmatzis, Ph.D., co-director of the Center for Individualized Medicine Biomarker Discovery Program, and final author on the study.

The Mayo Clinic team hopes this early research will lay the foundation for predicting which patients with mesothelioma are most likely benefit from immune checkpoint inhibitors. That class of drugs unleashes the power of each individual’s immune system to attack cancer cells.

Additional research is needed to verify the findings.

The study was funded by Leah and Richard Lommen, Mayo Clinic Center for Individualized Medicine Biomarker Discovery Program and National Institutes of Health grant NIH K12 CA90628.

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This article originally was published on the Center for Individualized Medicine blog on Nov. 26, 2018.

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Thu, Jan 17 6:00am · RIGHT 10K: Blazing a trail to health care's future

Article by Barbara Toman

This article originally appeared on the Center for Individualized Medicine blog

Mayo Clinic’s Center for Individualized Medicine (CIM) is nearing the finish line of the first stage of its unique RIGHT 10K study—an effort that doesn’t involve running shoes but nevertheless is paving the way to prescribing medications matched to a person’s genetic code.

RIGHT 10K is a clinical research project to genetically sequence more than10,000 individuals and place the results in those individuals’ electronic health records (EHRs). That information is critical because genetic differences can affect how a person processes and responds to medications. The right drug matched to a person’s genetic makeup could maximize the drug’s therapeutic benefit. However, the wrong drug or dosage can make a medication ineffective or even fatal.

Loading this “pharmacogenomic” information into EHRs is a huge challenge. Mayo’s early adoption of this strategy and comprehensive approach can guide providers as pharmacogenomics reshapes medical care.

Jessica Wright, Pharm.D. R.Ph.

“We’re now able to tell if patients could be at increased risk of therapeutic drug failure or devastating side effects. It’s critical to get that information preemptively into EHRs so that providers can be reliably notified of any adverse drug-gene interaction at the point of care,” says Jessica A. Wright, Pharm.D., R.Ph., a Mayo Clinic pharmacist specializing in pharmacogenomics.

Launched in 2016 in collaboration with Baylor College of Medicine and OneOme, a company that Mayo co-founded, RIGHT 10K will have entered data from all 10,000-plus patients into the EHR by the end of 2018. A OneOme interpretive report for 76 pharmacogenes are included in the data. Thirteen of those pharmacogenes can trigger an onscreen alert, if a physician inputs a prescription that might be ineffective or harmful for a particular patient based on their genes. The physician can then prescribe a different medication or adjust the dose.

The number of patients and pharmacogenes makes RIGHT 10K the most comprehensive effort to date to place pharmacogenomic information in individuals’ medical records. RIGHT 10K will systematically evaluate the impact of these clinical-decision alerts to determine if they improve prescribing decisions and ultimately health care. The lessons learned by Mayo Clinic can guide providers in the pharmacogenomics era.

Eric Matey, Pharm.D., R.Ph.

“Through RIGHT 10K we are training multiple healthcare providers at Mayo Clinic about pharmacogenomics. There is an opportunity for us to provide assistance and educate pharmacists elsewhere,” says Eric T. Matey, Pharm.D., R.Ph., a Mayo Clinic pharmacist specializing in pharmacogenomics.

Meeting the technical challenges

Complex pharmacogenomics information must be easily accessible for busy clinicians. “Having an effective computerized system is essential because it’s quite overwhelming for patients and their providers to remember pharmacogenomic testing results,” Dr. Wright says. “Pharmacogenomic information is stored in the EHR in ways that can enable alerts to clinicians and provide links to guidance when most needed.”

Another challenge is avoiding the overuse of alerts, which can interrupt workflow in busy clinics and possibly cause providers to ignore the popups. “Rather than bombarding providers, we limit the number of alerts they really need to pay attention to, in order to avoid harm to patients,” Dr. Matey says.

Mayo Clinic is also committed to designing EHRs that can easily incorporate new information —on a newly discovered pharmacogene, for example. A person’s genome doesn’t change; but our understanding of pharmacogenes improves as research advances. “Updating information in the electronic health records is a challenge we’re working on,” Dr. Wright says.

Although pharmacogenomics information will increasingly be considered an essential part of a patient’s medical record, EHRs will never replace clinicians.

“Pharmacogenomic results must not preclude clinical judgment. If a patient is doing well on a certain medication, but the pharmacogenomics test results are stating otherwise, the clinician should go ahead and use clinical judgment and continue the medication,” Dr. Matey says. “However, to avoid harm, we must work to give providers the information they need to make these clinical judgments.”

 

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