In the News
Gut Bacteria May Predict Risk of Life-Threatening Infections Following Chemotherapy
A new study led by researchers at the University of Minnesota and Nantes University Hospital in France shows that the bacteria in people’s gut may predict their risk of life-threatening blood infections following high-dose chemotherapy.
The study was published in Genome Medicine, a peer-reviewed open access journal.
About 20,000 cancer patients receive high-dose chemotherapy each year in preparation for bone marrow or stem cell transplants. Typically about 20 to 40 percent develop blood infections following the chemotherapy. Sadly, about 15 to 30 percent of those patients die as a result of the infections.
Bacteria are thought to enter the bloodstream through intestinal lesions due to chemotherapy-induced inflammation of the membrane lining the digestive tract. Once the infection begins, patients’ own immune systems are depleted and are often unable to fight off the pathogens and antibiotics often don’t work.
There are currently no good ways to predict which patients will acquire a bloodstream infection. Antibiotic regimens vary widely between clinics. In some clinics, all patients are given preventative antibiotics throughout their chemotherapy. In other clinics, few patients are given preventative antibiotics because the antibiotics can lead to increased antibiotic resistance in the patients.
In this study, the researchers set out to understand how the starting configuration of the gut bacteria, before the patient begins treatment, relates to risk of bloodstream infection. They collected fecal samples from 28 patients with non-Hodgkin’s lymphoma before the patients began chemotherapy. The researchers sequenced the bacterial DNA to measure the health of the bacterial ecosystem in each patient’s gut.
Eleven of the 28 subjects acquired a bloodstream infection following their chemotherapy, but interestingly the researchers found that those patients may have had more than bad luck going against them. They had significantly different mixtures of gut bacteria than the patients who did not get infections.
Using computational tools, the researchers then created an algorithm that can learn which bacteria are good and bad from studying one set of patients, and can then predict whether a new patient it has not seen before will get an infection, with around 85 percent accuracy.
“This method worked even better than we expected because we found a consistent difference between the gut bacteria in those who developed infections and those who did not,” said the study’s co-author Dan Knights, an assistant professor in the University of Minnesota’s Department of Computer Science and Engineering and the Biotechnology Institute.
“This research is an early demonstration that we may be able to use the bugs in our gut to predict infections and possibly develop new prognostic models in other diseases,” Knights added.
While the predictive model used in this study was robust, the researchers caution that their findings are still based on a limited number of patients with a single type of chemotherapy at a single clinic. They say the next step is to validate their approach in a much larger cohort including patients with different cancer types, different treatment types, and from multiple treatment centers.
“We still need to determine if these bacteria are playing any kind of causal role in the infections, or if they are simply acting as biomarkers for some other predisposing condition in the patient,” said study co-author Emmanuel Montassier, a researcher at the Nantes University Hospital and former researcher at the University of Minnesota.
The study was supported by Nantes University Hospital Grant (BRD/10/04-Q and the Robert Tournut award of the French National Society of Gastroenterology.
To read the full research study entitled “Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection,” visit the Genome Medicine website.
Yoga and Aquatic Exercise Can Help Combat MS Symptoms
Exercise can have a positive influence on certain symptoms of multiple sclerosis: Patients who do yoga and aquatic exercise suffer less from fatigue, depression, and paresthesia, as reported by researchers from the University of Basel and the Psychiatric University Clinics Basel in a joint study with colleagues in Iran.
Multiple sclerosis (MS) is a chronic progressive auto-immune disease in which the body's own immune system attacks the nervous tissue, potentially resulting in movement disorders. Other typical symptoms of MS include physical and mental fatigue as well as faintness, depression, and paresthesia such as pins and needles, itchiness and, numbness.
Increased risk of depression
In a random trial, researchers from Basel and Kermanshah (Iran) have now shown that these symptoms significantly improved after an eight-week program of yoga and aquatic exercise. In comparison to the control group, fatigue, depression, and paresthesia were significantly reduced in patients who took part in a three-times weekly training program. In the non-exercising group, the likelihood of moderate to severe depression was 35-fold higher than in the groups who had done yoga or aquatic exercise.
Fifty-four women with MS and an average age of 34 were assigned to one of three groups: yoga, aquatic exercise, or no exercise. Before and after the trial, patients were asked to complete a questionnaire about their symptoms. All patients continued with their existing treatment, including any medication taken to regulate the immune system.
Exercise as a complementary therapy
"Exercise training programs should be considered in the future as possible complements to standard MS treatments," write the researchers. Researchers from the Kermanshah University of Medical Sciences in Iran, the Psychiatric University Clinics (UPK Basel, Center for Affective, Stress and Sleep Disorders) and the University of Basel's Department of Sport, Exercise and Health took part in the study.
Does Exercise Benefit Cancer Patients?
Good nutrition and regular exercise combined are an effective way to reduce the risk of cancer and to prevent its recurrence. “This has been proven over and over,” said Carol DeNysschen, associate professor and chair of the Health, Nutrition, and Dietetics Department at Buffalo State. “If we could only motivate people to eat better and move more, we’d have so much less chronic disease.”
The Academy of Nutrition and Dietetics Foundation awarded the 2016 Abbott Nutrition Award in Women’s Health to DeNysschen in April. The annual award recognizes a dietitian who has made “significant contributions to the importance of nutrition in women’s health.”
DeNysschen is a registered dietitian who holds a master’s degree in public health. She began working with breast cancer survivors at Roswell Park Cancer Institute while earning a doctorate in exercise science at the University at Buffalo. “I’ve become interested in the effects of exercise on this group of patients,” said DeNysschen, “and our research interests are extending into patients with other kinds of cancers. We expect to begin a pilot study related to bladder cancer and exercise.”
If it’s hard for most adults to improve their diet and exercise habits, it’s especially difficult for cancer patients and survivors. “The cancer treatments lead to fatigue,” said DeNysschen, “and of course, if you feel tired, the last thing you want to do is exercise.”
But DeNysschen’s research suggests that exercise can minimize the side effects of some drugs used in treating cancer. A pilot study that looked at the effect of exercise on breast cancer patients taking drugs known as aromatase inhibitors (AIs) showed that exercise diminished the joint pain experienced by some patients. “The problem is that patients stop taking the AIs because of the pain,” said DeNysschen, “but the AIs reduce the risk of cancer recurring.”
Each participant was assigned one of three exercise schedules based on the individual’s fitness level. Each 8-week exercise regime included a video DeNysschen created that demonstrated resistance exercises, flexibility exercises, and—because joint pain in the hand and fingers is a common complaint for these patients—hand exercises. The exercises increased incrementally every two weeks. “We called every participant once a week to see how she was doing and to provide support and encouragement,” said DeNysschen.
The pilot study’s results were promising. Patients reported not only less pain but also improved quality of life and greater ease performing daily activities. “It’s just a start,” said DeNysschen, “but it’s a promising start.”
A healthy diet—a plant-based diet that includes five servings of fruits and vegetables daily—goes hand-in-hand with exercise. “They work together synergistically,” said DeNysschen, interlocking her fingers to illustrate her point. “Eating well is good, and moving is good, but to get the most out of a good diet and regular exercise, you need to do both.”
People who get cancer sometimes feel that they have lost control of their lives, DeNysschen has noticed. “If we can intervene and help patients change their diet and exercise habits, it may help to reestablish a sense of control,” she said. “For some people, establishing new habits while recovering from cancer can be empowering.”
Cholesterol Levels, Not Statins, Influence Colorectal Cancer Risk
Long-term use of the cholesterol-lowering drugs known as statins does not appear to decrease a patient's risk of colorectal cancer, suggests a new, large case-control study from Penn Medicine researchers published in PLOS Medicine. The observational analysis of over 100,000 patients' medical records suggests it is cholesterol levels that influence risk, not the much-debated statins, and that "indication bias" may explain the link between the widely-used cardiovascular drugs and risk. Such bias occurs when the indication (high cholesterol, in this case) being treated with a drug is also associated with the outcome of interest (colorectal cancer).
"There appears to be an artificially protective effect of statins," said Ronac Mamtani, MD, MSCE, an assistant professor of Hematology/Oncology from the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center, and lead author of the study. "Although the risk of colorectal cancer was lower in statin users versus non-users, when we compared those who continued statin therapy versus those who discontinued the therapy, such that each group shared the same indication for statin therapy, there was no difference in risk."
Both statin use and high cholesterol have been linked to a lower colorectal cancer risk, but it has remained unclear which may be responsible for the apparent beneficial effects.
Blood cholesterol levels were inversely related to colorectal cancer risk: the authors found that the higher the cholesterol level, the lower the risk for patients—regardless of statin use. The researchers also found that an unexplained drop in cholesterol levels one year before a cancer diagnosis increased the risk of cancer in both statin users and non-users.
The findings point to a bigger role of cholesterol levels on cancer risk that could potentially serve as a blood biomarker to help diagnose colorectal cancer earlier.
Ben Boursi, MD, a postdoctoral fellow in the Perelman School of Medicine, and Yu-Xiao Yang, MD, MSCE, an associate professor of Medicine and Epidemiology at Penn, are senior authors on the paper.
Statins are a common cholesterol-lowering treatment strategy for the management of patients at risk for coronary heart disease. Previous studies have also shown a potential reduction in cancer risk for people who take the drugs; however, they did not account for the blood cholesterol level on cancer risk, the authors said.
In the new study, the researchers compared statin use and blood cholesterol level between 22,163 patients with colorectal cancer and 86,538 patients without colorectal cancer (controls) from a database of electronic records of over 10 million patients from primary care practices in the United Kingdom.
They confirmed findings from previous studies that showed a decreased risk of colorectal cancer in statin users compared to non-users. However, they found that the difference in the risk of colorectal cancer was not significantly different between those patients who continued statin therapy and those who discontinued (OR, 0.98; 95% CI, 0.79-1.22). Furthermore, for every 1 mmol/L (~38.6 mg/dl) increase in total cholesterol level, authors observed a 10 percent decreased risk of colorectal cancer.
Additionally, they observed that decreases in total serum cholesterol (>1 mmol/L) at least a year before the cancer diagnosis were associated with 1.25-fold and 2.36-fold increased risk of colorectal cancer in users and nonusers, respectively.
"Together, these data demonstrate a complex association between statins, cholesterol, and colorectal cancer," Mamtani said. "While unexplained decreases in blood total cholesterol should alert physicians to consider colon cancer as one potential explanation, future studies are needed to determine the utility of blood cholesterol as a marker for early detection of colon cancer."
Co-authors on the paper include James D Lewis, Frank I Scott, Tariq Ahmad, David Goldberg, and Jashodeep Datta.
The study was supported by National Cancer Institute grant (K23-CA187185).