232 CNO REPORT 04 JUL 2016
Release Date 04 JUL 2016
Draft Report Compiled by
In this issue:
1. New study finds link between omega-3 supplementation and reduced hospital stays
2. Diet high in fiber and vitamin A key to preventing allergies to peanuts and other triggers
3. Study links omega-3s to reduced mortality
4. Hops could help reduce breast cancer risk
5. Broccoli sprout extract may protect against oral cancer recurrence
6. Beneficial bacteria may protect breasts from cancer
7. Chronic fatigue syndrome is in your gut, not your head
8. USF professor: No association between ‘bad cholesterol’ and elderly deaths
9. Lower levels of coenzyme Q10 in blood associated with multiple system atrophy
10. What effect does oral aloe vera have on diabetes?
11. Parsley and dill help fight cancer, research shows
12. Allergy-causing ‘bad guy’ cells unexpectedly prove life-saving in C. difficile
13. Rio athletes may benefit from ‘leaky gut’ therapy
14. Cravings for high-calorie foods may be switched off in the brain by new supplement
15. Prenatal exposure to paracetamol may increase autism spectrum symptoms
Public Release: 21-Jun-2016
New study finds link between omega-3 supplementation and reduced hospital stays
Patients spent an average of 2.4 fewer days in hospital
A new meta-analysis published in Clinical Nutrition found that cardiac surgery patients who received omega-3 polyunsaturated fatty acids (compared to placebo) in advance of surgery experienced reduced postoperative cardiac arrhythmias and significantly reduced the length of hospital stay by up to 2.4 days. The results are based on 11 RCT’s with 1038 patients.
“Omega-3s are well known for their benefits on cardiovascular health, including a reduced risk of arrhythmias and reduced mortality in patients with recent myocardial infarction or cardiac failure,” said co-author Dr. Pascal L. Langlois from the Department of Anesthesiology and Reanimation, Faculty of Medicine and Health Sciences at Sherbrooke University. “Furthermore, they exhibit interesting anti-inflammatory properties and modulate the immune system.”
This study implies a reduction in hospital utilization and overall healthcare costs, and supports an existing body of research demonstrating the heart health benefits of omega-3s.
The reduced length of hospital stay in this study was likely associated with the tendency of the omega-3 group to experience a reduction in postoperative atrial fibrillation, according to the authors. The exact mechanism associated with this benefit is unknown, but it is widely believed to be due to the omega-3s’ anti-inflammatory and anti-arrhythmic properties.
Public Release: 21-Jun-2016
Diet high in fiber and vitamin A key to preventing allergies to peanuts and other triggers
Eating a diet rich in fibre can actually shape the immune system to reduce allergies to substances such as peanuts, new research shows.
The study, led by Australian scientists, suggests that a simple bowl of bran and some dried apricots in the morning could prevent allergies. It also reveals how the immune system works with the good bacteria in the gut to help protect against life threatening allergic responses.
The Monash University-led study, published today in the journal Cell Reports, revealed that it may be a lack of fibre in our diets that’s causing this deadly rise in allergies. By determining how this happens, the researchers have suggested potential treatments to prevent, or possibly even reverse food allergies. They suggest that allergy treatments could use probiotics (beneficial bacteria) that recolonize the gut, or prebiotics (healthy foodstuffs) that could work together to prevent or reverse allergies.
The research, performed largely by Jian Tan, a PhD student at the Monash Biomedicine Discovery Institute, found that mice allergic to peanuts were protected against the allergy when fed a high-fibre diet. In particular, the fibre appears to act by reshaping the gut and colon microbiota.
The study revealed that eating a high-fibre diet actually changes the gut microbiota, the bacteria in the gut, to protect against food allergies. The transfer of these ‘good bacteria’ to mice without these bacteria could reduce the symptoms of food allergies. The microbiota in the gut assist the immune system in resisting allergies through the breaking down of fibre into short-chain fatty acids. This opens up a potential route for drug therapy for allergies by delivering short-chain fatty acids as a treatment.
The scientists, from the laboratory of Professor Charles Mackay, further unravelled how a high fibre diet protects against allergies. They found that short-chain fatty acids boosted a particular subset of the immune system called dendritic cells, which control whether an allergic response against a food allergen happens or not. Effectively, increased levels of short-chain fatty acids switch these cells to stop the allergic response, while a lack of fibre may have an opposite effect. These specialised dendritic cells require vitamin A, another factor which can only be obtained through the diet, and is high in vegetables and fruits.
While deficiency of vitamin A in adults is unusual, the researchers suggest that less than ideal levels of vitamin A in addition to short-chain fatty acids, could promote food allergies in infants. This may explain why the highest prevalence of allergies occurs in children and infants. Mr Tan said the study had not only revealed how the immune system fails when a person becomes allergic, but how the immune system can be helped through diet, to prevent or lessen the effects of allergies. He said the next step was to conduct trials with humans to determine how a high-fibre diet can protect against challenges with allergic foodstuffs.
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 100 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
Public Release: 22-Jun-2016
Study links omega-3s to reduced mortality
Meta analysis shows 9 percent reduced risk associated with omega-3 intake
A recent meta-analysis in Scientific Reports supports a link between EPA and DHA omega-3 intake and a reduced risk of death by any cause. The meta-analysis included 11 studies involving 371,965 participants and 31,185 death events, with a subset of the studies being used for different analyses.
In the analysis of n-3 LCPUFA intake, there was a 9% reduced risk of all-cause death associated with high versus low omega-3 intake. In the dose-response analysis, an increase in EPA/DHA intake of 300 mg/day was associated with a 6% lower risk of all-cause mortality. These findings suggest that both dietary and circulating n-3 LCPUFA are shown to be significantly associated with reduced risk of all-cause mortality.
According to study author Manfred Eggersdorfer, “The meta-analysis of 11 prospective observational studies demonstrates that each 1% increment of omega-3s in total fatty acids in blood may be associated with a 20% decrease in risk of all-cause mortality. This is an important finding for the potential contribution of adequate omega-3 intake to public health.”
Public Release: 22-Jun-2016
Hops could help reduce breast cancer risk
American Chemical Society
Hops, the flower cones used in beer-making, are also found in dietary supplements designed to help treat post-menopausal symptoms and other conditions. Scientists are now investigating whether an extract from the plant could also help fend off breast cancer. In the ACS journal Chemical Research in Toxicology, one team reports new lab tests on breast cells that support this possibility.
In the U.S., breast cancer is one of the most commonly diagnosed cancers in women. Exposure to estrogen has long been considered one of the risk factors associated with developing the disease, particularly in post-menopausal women. Women who are undergoing menopause often use hormone replacement therapy, or HRT, to alleviate symptoms such as hot flashes. But HRT has been linked to an increased risk of breast cancer and heart disease, so some women are turning to hops supplements, which contain phytoestrogens, as a natural alternative. However, their effect on cancer risk is unclear. Preliminary lab studies have suggested that certain active compounds from hops could have protective properties. Building on this lead, Judy L. Bolton and colleagues used an enriched hop extract to test its effects on estrogen metabolism, one of the processes in the development of breast cancer.
The researchers applied the extract to two different breast cell lines to see how they would affect estrogen metabolism. One particular hops compound called 6-prenylnaringenin, or 6-PN, boosted the cells’ detoxification pathway that studies have associated with a lower risk for breast cancer. Thus the results suggest that 6-PN could have anti-cancer effects, although more studies would be needed to further investigate this possibility, the researchers say.
Public Release: 23-Jun-2016
Broccoli sprout extract may protect against oral cancer recurrence
University of Pittsburgh Schools of the Health Sciences
PITTSBURGH, June 23, 2016 – Potent doses of broccoli sprout extract activate a “detoxification” gene and may help prevent cancer recurrence in survivors of head and neck cancer, according to a trial by the University of Pittsburgh Cancer Institute, partner with UPMC CancerCenter, confirming preliminary results presented last year at the American Association for Cancer Research Annual Meeting.
It is the first study demonstrating that the extract protects against oral cancer, with the results of human, animal and laboratory tests reported today in the journal Cancer Prevention Research. This research is funded through Pitt’s Specialized Program of Research Excellence grant in head and neck cancer from the National Cancer Institute.
“With head and neck cancer, we often clear patients of cancer only to see it come back with deadly consequences a few years later,” said lead author Julie Bauman, M.D., M.P.H., co-director of the UPMC Head and Neck Cancer Center of Excellence. “Unfortunately, previous efforts to develop a preventative drug to reduce this risk have been inefficient, intolerable in patients and expensive. That led us to ‘green chemoprevention’–the cost-effective development of treatments based upon whole plants or their extracts.”
Cruciferous vegetables, such as broccoli, cabbage and garden cress, have a high concentration of the naturally occurring molecular compound sulforaphane, which previously has been shown to protect people against environmental carcinogens.
Dr. Bauman and her colleagues treated human head and neck cancer cells in the laboratory with varying doses of sulforaphane and a control, and compared them to normal, healthy cells that line the throat and mouth. The sulforaphane induced both types of cells to increase their levels of a protein that turns on genes that promote detoxification of carcinogens, like those found in cigarettes, and protect cells from cancer.
In a small preclinical trial, 10 healthy volunteers drank or swished fruit juice mixed with broccoli sprout extract for several days. The volunteers had no significant problems tolerating the extract and the lining of their mouths showed that the same protective genetic pathway activated in the laboratory cell tests was activated in their mouths, meaning that the sulforaphane was absorbed and directed to at-risk tissue.
Dr. Bauman also collaborated with senior author Daniel E. Johnson, Ph.D., professor of medicine at Pitt and a senior scientist in the UPCI Head and Neck Cancer Program, to see how the extract performed in mice predisposed to head and neck cancer. The mice who received the sulforaphane developed far fewer tumors than their counterparts who did not receive the extract.
The results of the mouse, human and lab studies have been so successful that Dr. Bauman has started a larger clinical trial in volunteers previously cured of head and neck cancer. These participants are taking capsules containing broccoli seed powder, which is more convenient to take regularly than the extract mixed with juice.
“Head and neck cancers account for approximately 3 percent of all cancers in the U.S., but that burden is far greater in many developing countries,” said Dr. Bauman. “A preventative drug created from whole plants or their extracts may ease the costs of production and distribution, and ultimately have a huge positive impact on mortality and quality of life in people around the world.”
Public Release: 24-Jun-2016
Beneficial bacteria may protect breasts from cancer
American Society for Microbiology
Washington, DC – June 24, 2016 – Bacteria that have the potential to abet breast cancer are present in the breasts of cancer patients, while beneficial bacteria are more abundant in healthy breasts, where they may actually be protecting women from cancer, according to Gregor Reid, PhD, and his collaborators. These findings may lead ultimately to the use of probiotics to protect women against breast cancer. The research is published in the ahead of print June 24 in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.
In the study, Reid’s PhD student Camilla Urbaniak obtained breast tissues from 58 women who were undergoing lumpectomies or mastectomies for either benign (13 women) or cancerous (45 women) tumors, as well as from 23 healthy women who had undergone breast reductions or enhancements. They used DNA sequencing to identify bacteria from the tissues, and culturing to confirm that the organisms were alive. Reid is Professor of Surgery, and Microbiology & Immunology at Western University and Director, Canadian Centre for Human Microbiome and Probiotic Research at Lawson Health Research Institute in London, Ontario, Canada.
Women with breast cancer had elevated levels of Escherichia coli and Staphylococcus epidermidis, are known to induce double-stranded breaks in DNA in HeLa cells, which are cultured human cells. “Double-strand breaks are the most detrimental type of DNA damage and are caused by genotoxins, reactive oxygen species, and ionizing radiation,” the investigators write. The repair mechanism for double-stranded breaks is highly error prone, and such errors can lead to cancer’s development.
Conversely, Lactobacillus and Streptococcus, considered to be health-promoting bacteria, were more prevalent in healthy breasts than in cancerous ones. Both groups have anticarcinogenic properties. For example, natural killer cells are critical to controlling growth of tumors, and a low level of these immune cells is associated with increased incidence of breast cancer. Streptococcus thermophilus produces anti-oxidants that neutralize reactive oxygen species, which can cause DNA damage, and thus, cancer.
The motivation for the research was the knowledge that breast cancer decreases with breast feeding, said Reid. “Since human milk contains beneficial bacteria, we wondered if they might be playing a role in lowering the risk of cancer. Or, could other bacterial types influence cancer formation in the mammary gland in women who had never lactated? To even explore the question, we needed first to show that bacteria are indeed present in breast tissue.” (They had showed that in earlier research.)
But lactation might not even be necessary to improve the bacterial flora of breasts. “Colleagues in Spain have shown that probiotic lactobacilli ingested by women can reach the mammary gland,” said Reid. “Combined with our work, this raises the question, should women, especially those at risk for breast cancer, take probiotic lactobacilli to increase the proportion of beneficial bacteria in the breast? To date, researchers have not even considered such questions, and indeed some have balked at there being any link between bacteria and breast cancer or health.”
Besides fighting cancer directly, it might be possible to increase the abundance of beneficial bacteria at the expense of harmful ones, through probiotics, said Reid. Antibiotics targeting bacteria that abet cancer might be another option for improving breast cancer management, said Reid.
In any case, something keeps bacteria in check on and in the breasts, as it does throughout the rest of the body, said Reid. “What if that something was other bacteria–in conjunction with the host immune system? We haven’t answered this question, but it behooves experts in the field to now consider the potential.”
microbial sciences to diverse audiences.
Public Release: 27-Jun-2016
Chronic fatigue syndrome is in your gut, not your head
Physicians have been mystified by chronic fatigue syndrome, a condition where normal exertion leads to debilitating fatigue that isn’t alleviated by rest. There are no known triggers, and diagnosis requires lengthy tests administered by an expert.
Now, for the first time, Cornell University researchers report they have identified biological markers of the disease in gut bacteria and inflammatory microbial agents in the blood.
In a study published June 23 in the journal Microbiome, the team describes how they correctly diagnosed myalgic encephalomyeletis/chronic fatigue syndrome (ME/CFS) in 83 percent of patients through stool samples and blood work, offering a noninvasive diagnosis and a step toward understanding the cause of the disease.
“Our work demonstrates that the gut bacterial microbiome in chronic fatigue syndrome patients isn’t normal, perhaps leading to gastrointestinal and inflammatory symptoms in victims of the disease,” said Maureen Hanson, the Liberty Hyde Bailey Professor in the Department of Molecular Biology and Genetics at Cornell and the paper’s senior author. “Furthermore, our detection of a biological abnormality provides further evidence against the ridiculous concept that the disease is psychological in origin.”
“In the future, we could see this technique as a complement to other noninvasive diagnoses, but if we have a better idea of what is going on with these gut microbes and patients, maybe clinicians could consider changing diets, using prebiotics such as dietary fibers or probiotics to help treat the disease,” said Ludovic Giloteaux, a postdoctoral researcher and first author of the study.
In the study, Ithaca campus researchers collaborated with Dr. Susan Levine, an ME/CFS specialist in New York City, who recruited 48 people diagnosed with ME/CFS and 39 healthy controls to provide stool and blood samples.
The researchers sequenced regions of microbial DNA from the stool samples to identify different types of bacteria. Overall, the diversity of types of bacteria was greatly reduced and there were fewer bacterial species known to be anti-inflammatory in ME/CFS patients compared with healthy people, an observation also seen in people with Crohn’s disease and ulcerative colitis.
At the same time, the researchers discovered specific markers of inflammation in the blood, likely due to a leaky gut from intestinal problems that allow bacteria to enter the blood, Giloteaux said.
Bacteria in the blood will trigger an immune response, which could worsen symptoms.
The researchers have no evidence to distinguish whether the altered gut microbiome is a cause or a whether it is a consequence of disease, Giloteaux added.
In the future, the research team will look for evidence of viruses and fungi in the gut, to see whether one of these or an association of these along with bacteria may be causing or contributing to the illness.
The study was funded by the National Institutes of Health.
Public Release: 27-Jun-2016
USF professor: No association between ‘bad cholesterol’ and elderly deaths
Systematic review of studies of over 68,000 elderly people also raises questions about the benefits of statin drug treatments
University of South Florida (USF Innovation)
TAMPA, Fla. (June 27, 2016) – A University of South Florida professor and an international team of experts have found that older people with high levels of a certain type of cholesterol, known as low-density lipoprotein (LDL-C), live as long, and often longer, than their peers with low levels of this same cholesterol.
The findings, which came after analyzing past studies involving more than 68,000 participants over 60 years of age, call into question the “cholesterol hypothesis,” which previously suggested people with high cholesterol are more at risk of dying and would need statin drugs to lower their cholesterol.
Appearing online this month in the open access version of the British Medical Journal, the research team’s analysis represents the first review of a large group of prior studies on this issue.
“We have known for decades that high total cholesterol becomes a much weaker risk for cardiovascular disease with advancing age,” said Diamond. “In this analysis, we focused on the so-called “bad cholesterol” which has been blamed for contributing to heart disease.”
According to the authors, either a lack of association or an inverse relationship between LDL-C and cardiovascular deaths was present in each of the studies they evaluated. Subsequently, the research team called for a reevaluation of the need for drugs, such as statins, which are aimed at reducing LDL-C as a step to prevent cardiovascular diseases.
“We found that several studies reported not only a lack of association between low LDL-C, but most people in these studies exhibited an inverse relationship, which means that higher LDL-C among the elderly is often associated with longer life,” said Diamond.
Diamond also points out the research that suggests that high cholesterol may be protective against diseases which are common in the elderly. For example, high levels of cholesterol are associated with a lower rate of neurological disorders, such as Parkinson’s disease and Alzheimer’s disease. Other studies have suggested that high LDL-C may protect against some often fatal diseases, such as cancer and infectious diseases, and that having low LDL-C may increase one’s susceptibility to these diseases.
“Our results pose several relevant questions for future,” said study leader and co-author health researcher Dr. Uffe Ravnskov. “For example, why is total cholesterol a factor for cardiovascular disease for young and middle-age people, but not for the elderly? Why do a substantial number of elderly people with high LDL-C live longer than elderly people with low LDL-C?”
Diamond and colleagues have published a number of studies relating to the use and possible misuse of statins for treating cholesterol. Those studies, including their recent paper published in the medical journal Expert Review of Clinical Pharmacology, which demonstrated that the benefits of taking statins have been exaggerated and are misleading.
“Our findings provide a contradiction to the cholesterol hypothesis,” concluded Diamond. “That hypothesis predicts that cardiovascular disease starts in middle age as a result of high LDL-C cholesterol, worsens with aging, and eventually leads to death from cardiovascular disease. We did not find that trend. If LDL-C is accumulating in arteries over a lifetime to cause heart disease, then why is it that elderly people with the highest LDL-C live the longest? Since people over the age of 60 with high LDL-C live the longest, why should we lower it?”
– USF –
Public Release: 27-Jun-2016
Lower levels of coenzyme Q10 in blood associated with multiple system atrophy
The JAMA Network Journals
The neurodegenerative disease known as multiple system atrophy (MSA) affects both movement and involuntary bodily functions. Questions have been raised about the potential role of coenzyme Q10 (CoQ10) insufficiency in the development of MSA. Little is known about blood levels of CoQ10 in patients carrying either COQ2 mutations or no mutations.
Shoji Tsuji, M.D., Ph.D., of the University of Tokyo, Japan, and coauthors explored whether there are associations of levels of CoQ10 in the blood and MSA, in a new article published online by JAMA Neurology.
The study included 44 Japanese patients with MSA (average age almost 64) and, for comparison, 39 Japanese control patients (average age about 60).
The authors report their data showed decreased levels of blood CoQ10 in patients was associated with MSA regardless of the COQ2 genotype. The authors suggest this may support the idea that CoQ10 supplementation may be beneficial for patients with MSA. However, they acknowledge study limitations and caution that more studies are needed.
“Prospective cohort studies are warranted to determine the longitudinal effects of plasma levels of CoQ10 on the development of MSA. Furthermore, future clinical trials of supplementation with CoQ10 in patients with MSA are required to confirm our hypothesis,” the article concludes.
Public Release: 28-Jun-2016
What effect does oral aloe vera have on diabetes?
Mary Ann Liebert, Inc./Genetic Engineering News
New Rochelle, NY, June 28, 2016 — A meta-analysis of studies in people with diabetes and pre-diabetes has shown that oral aloe vera use was associated with significant decreases in both fasting blood glucose (FBG) and hemoglobin A1c (HbA1c). The data indicate that people with a FBG >200 mg/dL may benefit the most, according to an article in The Journal of Alternative and Complementary Medicine, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free for download on The Journal of Alternative and Complementary Medicine website until July 29, 2016.
In the article “Reduction of Fasting Blood Glucose and Hemoglobin A1c Using Oral Aloe Vera: A Meta-Analysis,” William Dick, Emily Fletcher, and Sachin Shah, David Grant Medical Center, Travis Air Force Base, Fairfield, CA and Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA describe their analysis of data from nine studies to assess the effectiveness of oral aloe vera consumption in diabetes. They report significant reductions in FBG and HbA1c of 46.6 mg/dL and 1.05%, respectively, and review the proposed mechanisms that could account for these anti-diabetic effects.
Public Release: 28-Jun-2016
Parsley and dill help fight cancer, research shows
A team of Russian scientists proposed an efficient approach to a novel agents with anticancer activity. A synthesis of these compounds is based on compounds extracted from parsley and dill seeds
Moscow Institute of Physics and Technology
A team of Russian scientists from Moscow Institute of Physics and Technology (MIPT), the N. D. Zelinsky Institute of Organic Chemistry (RAS), the Institute of Developmental Biology (RAS), and the Institute of Cell Biophysics (RAS) proposed an efficient approach to a novel agents with anticancer activity. A synthesis of these compounds is based on compounds extracted from parsley and dill seeds. The results of the study have been published in the Journal of Natural Products.
“Both improvement of existing therapies and search for innovative approaches are essential components of a quest to treat cancer. Our combined team developed a simple method of producing glaziovianin A and its structural analogs, which inhibit the growth of human tumor cells, using feasible building blocks from nature. Furthermore, evaluation of these novel agents in vivo using our validated sea urchin embryo assays yielded several promising candidates selectively affecting tubulin dynamics” says MIPT professor Alexander Kiselev.
No growth for cancer cells
Currently, the main method of medical treatment for cancer is chemotherapy. The treatment uses antimitotics, which inhibit the growth of cancer cells by disrupting the process of cell division (mitosis).
Cancer cells divide much more frequently than normal cells and therefore they are more susceptible to the effects of antimitotics. For example, the number of melanoma cells doubles every 3 days, whereas the number of their healthy progenitors melanocytes increases by 15%, even when cell division is stimulated.
Microtubules play an important role in mitosis. They are composed of a protein called tubulin.
Antimitotics bind tubulin and affect microtubule dynamics disrupting cell cycle to result in arrested cell division and subsequent selective death.The study focused on the potent antimitotic agent glaziovianin A isolated from the leaves of the Brazilian tree Ateleia glazioviana Baill.
The reported synthesis of this agent is rather laborious and requires expensive precursors (substances that participate in reactions necessary for obtaining an end product) and catalysts (which accelerate chemical reactions). The authors proposed a novel and more efficient six-stage synthesis process (the normal process has nine stages) for glaziovianin A. Precursors for the process were derived from the seeds of common plants, namely parsley and dill.
In addition to glaziovianin A, a number of its structural analogs were synthesized in order to help find analogues with favorable antimitotic properties. The antitumor activity was tested via two independent methods using the sea urchin embryos and human cancer cells.
On sea urchins and cancer cells
The embryos of sea urchins were used to mimic actively dividing tumor cells dependent on tubulin dynamics. The scientists added test substances to an aqueous medium with the embryos and determined the concentrations at which the rate of division changes and when it comes to a complete stop. The lower the concentration, the greater the antimitotic activity the substance has. As the authors of the study established previously, when division is disrupted due to specific antitubulin activity of an agent, the embryos of sea urchins start spinning axially. Conveniently, this effect can be easily observed using a common light microscope.
Using the embryos, scientists are able to determine several important parameters essential for an anti-cancer molecule ‘in one shot.” These include a specific antimitotic effect, solubility, overall toxicity and biomembrane permeability.
To further confirm the antitumor effect of active molecules, they were studied with various human cancer cells, ex. lung carcinoma, melanoma, prostate, breast, colon, and ovarian cancers. The experiments showed that the test substances were effective at limiting the growth of melanoma cells, and non-toxic to healthy blood cells used as a control. Detailed structure-activity relationship studies in both assay systems converged on the parent glasiovianin A to be the most active anti-tubulin agent. Future plans include both optimization of the compound to improve its metabolic stability and solubility as well as human xenograft studies in mice to confirm anti-tumor activity and clinical development potential.
Public Release: 29-Jun-2016
Allergy-causing ‘bad guy’ cells unexpectedly prove life-saving in C. difficile
Finding ‘as unexpected as it is important,’ with ‘immediate implications for therapy’
· C. diff kills one in seven infected in North America
· But probiotics that ensure the presence of certain cells in the gut may stave off infection
· Finding ‘as unexpected as it is important,’ with ‘immediate implications for therapy’
Researchers at the University of Virginia School of Medicine have identified immune cells vital for protecting us from potentially fatal C. difficile infection. Surprisingly, those cells are often vilified for their role in causing asthma and allergies. But when it comes to C. difficile, they could be the difference in life and death.
With the discovery, the researchers have answered some of the greatest questions about C. diff, shed light on why antibiotics lead to severe C. diff and identified a potential way for doctors to prevent the life-threatening infection — and possibly other infections as well.
The Role of Antibiotics
Bill Petri, MD, PhD, chief of the Division of Infectious Diseases and International Health at the UVA Health System, hailed the discovery by UVA’s Erica L. Buonomo, PhD, and colleagues as “the most remarkable breakthrough I have participated in as a scientist.”
“Antibiotics are really important, and very often you have to give antibiotics, but you do it knowing that you’re predisposing your patient to another infection [C. difficile] that is potentially lethal. About one out of seven people with this infection dies in North America. So it’s a terrible dilemma for physicians,” Petri said. “This is not a common complication of antibiotics, but when it happens, it’s a very serious one. This work enables a potential long-term solution to that, which is probiotics to restore the natural state of the gut.”
There were almost half a million C. diff infections in the United States in 2011, and approximately 29,000 patients died within 30 days of infection, according to a study released last year by the U.S. Centers for Disease Control and Prevention. The agency has classified the bacterium as an “urgent threat,” noting the rise of a new epidemic strain in recent years that has made the infection even deadlier.
Kris Chadee, PhD, a professor at the University of Calgary who was not involved in UVA’s C. diff work, called the discovery “as unexpected as it is important,” noting that the finding “has immediate implications for therapy: Probiotics designed to restore the healthy gut microbiome should be an effective way to prevent this life-threatening infection.”
Understanding C. Difficile
C. difficile is primarily a hospital-acquired infection, and it predominantly affects the elderly, particularly elderly people on antibiotics. UVA’s discovery offers answers about why that is. The researchers showed that the gut bacteria stimulates the production of a protein called IL-25, which then recruits protective cells called eosinophils. As such, IL-25, the product of “good” bacteria, protects the lining of the gut from pathogens. Antibiotics, however, disrupt our body’s natural bacterial populations, leaving the gut lining vulnerable to C. diff and other infections.
Intriguingly, the researchers found an important and unexpected role for eosinophils, a type of white blood cells. These cells are often vilified for their role in causing both allergies and asthma, but in the battle against C. diff, they can be life-saving. IL-25, the UVA researchers show, protects us from C. diff by manufacturing eosinophils to guard the integrity of the gut lining.
“We found that if you deplete eosinophils, either genetically or by an antibody neutralization, you lost the integrity of the epithelial barrier in the gut,” Buonomo said. “Maintaining that barrier is very important for having a healthy response to C. difficile. It also prevents bacteria from spreading to other sites in the body, so if you have a breakdown in the barrier, you can have a septic response or bacteria in your blood or in other systemic organs.”
The findings suggest that researchers should be able to develop new probiotics that patients could take to ward off C. difficile. “We could end up that every person taking an antibiotic is taking a new probiotic that is specifically designed to maintain IL-25 and eosinophils,” Petri said.
Petri noted that Buonomo joined his lab while a graduate student at UVA, and he credited the discovery to the new perspective she brought. “Erica was a card-carrying immunologist before she came into my lab,” Petri recalled. “She came with an immunology mindset, and the lab wasn’t immunology focused at all. It’s changed. We’ve all seen the benefit of having that perspective, of looking at how the immune system is responding to the bacterial infection.”
Findings Published Online
The discovery has been described in a paper published online by the scientific journal Cell Reports. It was authored by Buonomo, Carrie A. Cowardin, Madeline G. Wilson, Mahmoud M. Saleh, Patcharin Pramoonjago and Petri.
Public Release: 29-Jun-2016
Rio athletes may benefit from ‘leaky gut’ therapy
A simple nutritional supplement could be the solution and useful for athletes taking part in the Rio Olympics 2016
University of Plymouth
‘Leaky gut’ is a condition where the thin mucosal barrier of the gut, which plays a role in absorbing nutrients and preventing large molecules and germs from the gut entering the blood stream, becomes less effective.
It is a particular problem for those taking part in heavy exercise or who are active in hot conditions. It can lead to ‘heat stroke’ (especially in military personnel deployed to countries with high temperatures) and gut symptoms in athletes.
A research team from Plymouth University Peninsula Schools of Medicine and Dentistry, the University of Kent, the University of Leicester and Aberystwyth University, have published a paper today, 29th June 2016, in the prestigious American Journal of Clinical Nutrition which claims that zinc carnosine (a health food product), taken alone or with bovine colostrum, may have value for athletes and prevent heat stroke in military personnel.
The team recruited eight volunteers who took part in a four-arm, double-blind placebo-controlled test. The volunteers were put into groups where each group received either the placebo, zinc carnosine, colostrum or zinc carnosine and colostrum for 14 days prior to standardised exercise taken two and 14 days after starting treatment. Among the changes that occurred in the athletes during heavy exercise was a two degree centigrade rise in body temperature, which may well have been a contributing factor in causing the increased leakiness of the gut.
The clinical trial went parallel to cell culture experiments to help understand the mechanisms behind how zinc carnosine and bovine colostrum worked.
The results showed that zinc carnosine improved the performance of the mucosal barrier of the gut, and that this improvement was enhanced when supplemented with bovine colostrum. Both are readily available from health food suppliers and the research team concluded that zinc carnosine taken alone or with bovine colostrum may have value for those affected by ‘leaky gut’.
One of the lead authors of the study was Professor Raymond Playford, a gastro-intestinal expert and Professor of Medicine from Plymouth University Peninsula Schools of Medicine and Dentistry.
He said: “The distinction between food products and pharmaceutical drugs is often blurred. Our research group is interested in using naturally-derived products to enhance gut health. Our findings – that zinc carnosine and/or colostrum are helpful in preventing leaky gut associated with heavy exercise – are exciting and underpinned by a thorough clinical trial supported by cell culture experiments.”
He added: “Not only has this application for athletic performance where gut symptoms can be problematic, it also has value for people exposed to high temperatures such as military personnel deployed to the Middle East. For athletes participating in this summer’s Olympic Games in Brazil our findings could be of immense help, given that they will be exercising at their peak in hot and humid conditions.”
Public Release: 1-Jul-2016
Cravings for high-calorie foods may be switched off in the brain by new supplement
Eating a type of powdered food supplement, based on a molecule produced by bacteria in the gut, reduces cravings for high-calorie foods such as chocolate, cake and pizza, a new study suggests
Imperial College London
Eating a type of powdered food supplement, based on a molecule produced by bacteria in the gut, reduces cravings for high-calorie foods such as chocolate, cake and pizza, a new study suggests.
Scientists from Imperial College London and the University of Glasgow asked 20 volunteers to consume a milkshake that either contained an ingredient called inulin-propionate ester, or a type of fibre called inulin.
Previous studies have shown bacteria in the gut release a compound called propionate when they digest the fibre inulin, which can signal to the brain to reduce appetite. However the inulin-propionate ester supplement releases much more propionate in the intestines than inulin alone.
After drinking the milkshakes, the participants in the current study underwent an MRI scan, where they were shown pictures of various low or high calorie foods such as salad, fish and vegetables or chocolate, cake and pizza.
The team found that when volunteers drank the milkshake containing inulin-propionate ester, they had less activity in areas of their brain linked to reward — but only when looking at the high calorie foods. These areas, called the caudate and the nucleus accumbens, found in the centre of the brain, have previously been linked to food cravings and the motivation to want a food.
The volunteers also had to rate how appealing they found the foods. The results showed when they drank the milkshake with the inulin-propionate ester supplement they rated the high calorie foods as less appealing.
In a second part of the study, which is published in July edition of the American Journal of Clinical Nutrition, the volunteers were given a bowl of pasta with tomato sauce, and asked to eat as much as they like. When participants drank the inulin-propionate ester, they ate 10 per cent less pasta than when they drank the milkshake that contained inulin alone.
In a previous research study by the same team, published in 2013, they found that overweight volunteers who added the inulin-propionate ester supplement to their food every day, gained less weight over six months compared to volunteers who added only inulin to their meals.
Professor Gary Frost, senior author of the study from the Department of Medicine at Imperial, said: “Our previous findings showed that people who ate this ingredient gained less weight — but we did not know why. This study is filling in a missing bit of the jigsaw — and shows that this supplement can decrease activity in brain areas associated with food reward at the same time as reducing the amount of food they eat.”
He added that eating enough fibre to naturally produce similar amounts of propionate would be difficult: “The amount of inulin-propionate ester used in this study was 10g – which previous studies show increases propionate production by 2.5 times. To get the same increase from fibre alone, we would need to eat around 60g a day. At the moment, the UK average is 15g.”
Claire Byrne, a PhD researcher also from the Department of Medicine explained that using inulin-propionate ester as a food ingredient may help prevent weight gain: “If we add this to foods it could reduce the urge to consume high calorie foods.” She added that some people’s gut bacteria may naturally produce more propionate than others, which may be why some people seem more naturally predisposed to gain weight.
Dr Tony Goldstone, co-senior author of the study from the Department of Medicine added: “This study adds to our previous brain imaging studies in people who have had gastric bypass surgery for obesity. These show that altering how the gut works can change not only appetite in general, but also change how the brain responds when they see high-calorie foods, and how appealing they find the foods to be.”
Dr Douglas Morrison, author of the paper from the Scottish Universities Environmental Research Centre at the University of Glasgow, commented: “We developed inulin-propionate ester to investigate the role of propionate produced by the gut microbiota in human health. This study illustrates very nicely that signals produced by the gut microbiota are important for appetite regulation and food choice. This study also sheds new light on how diet, the gut microbiome and health are inextricably linked adding to our understanding of how feeding our gut microbes with dietary fibre is important for healthy living.”
The research was funded by the National Institute for Health Research Imperial Biomedical Research Centre and the Biotechnology and Biological Sciences Research Council
Public Release: 1-Jul-2016
Prenatal exposure to paracetamol may increase autism spectrum symptoms
Oxford University Press
A new study has found that paracetamol (acetaminophen), which is used extensively during pregnancy, has a strong association with autism spectrum symptoms in boys and for both genders in relation to attention-related and hyperactivity symptoms.
The findings were published this week in the International Journal of Epidemiology. This is the first study of its kind to report an independent association between the use of this drug in pregnancy and autism spectrum symptoms in children. It is also the first study to report different effects on boys and girls. Comparing persistently to nonexposed children, the study has found an increase of 30 per cent in the risk of detriment to some attention functions, and an increase of two clinical symptoms of autism spectrum symptoms in boys.
Researchers in Spain recruited 2644 mother-child pairs in a birth cohort study during pregnancy. 88 per cent were evaluated when the child was one year old, and 79.9 per cent were evaluated when they were five years old. Mothers were asked about their use of paracetamol during pregnancy and the frequency of use was classified as never, sporadic, or persistent. Exact doses could not be noted due to mothers being unable to recall them exactly. 43 per cent of children evaluated at age one and 41 per cent assessed at age five were exposed to any paracetamol at some point during the first 32 weeks of pregnancy. When assessed at age five, exposed children were at higher risk of hyperactivity or impulsivity symptoms. Persistently exposed children in particular showed poorer performance on a computerised test measuring inattention, impulsivity and visual speed processing.
Boys also showed more autism spectrum symptoms when persistently exposed to paracetamol. Lead author Claudia Avella-Garcia, researcher at CREAL, an ISGlobal allied centre in Barcelona, explained that, “although we measured symptoms and not diagnoses, an increase in the number of symptoms that a child has, can affect him or her, even if they are not severe enough to warrant a clinical diagnosis of a neurodevelopmental disorder.”
Co-author Dr. Jordi Júlvez, also a researcher at CREAL, commented on the possible reasoning for the effects of paracetamol on neurodevelopment: “Paracetamol could be harmful to neurodevelopment for several reasons. First of all, it relieves pain by acting on cannabinoid receptors in the brain. Since these receptors normally help determine how neurons mature and connect with one another, paracetamol could alter these important processes. It can also affect the development of the immune system, or be directly toxic to some fetuses that may not have the same capacity as an adult to metabolize this drug, or by creating oxidative stress.”
There could also be an explanation for why boys are more likely to have autism spectrum symptoms: “The male brain may be more vulnerable to harmful influences during early life”, said Claudia Avella-Garcia. “Our differing gender results suggest that androgenic endocrine disruption, to which male brains could be more sensitive, may explain the association.”
The study concluded that the widespread exposure of infants to paracetamol in utero could increase the number of children with ADHD or autism spectrum symptoms. However, they stressed further studies should be conducted with more precise dosage measurements, and that the risks versus benefits of paracetamol use during pregnancy and early life should be assessed before treatment recommendations are made.