Up to 20% of the world’s population suffers from the irritable bowel syndrome (IBS), which causes stomach pain or severe discomfort after eating. This affects their quality of life. Gluten-free and other diets can provide some relief, but why this works is a mystery, since the patients are not allergic to the foods in question, nor do they have known conditions such as coeliac disease.

“Very often these patients are not taken seriously by physicians, and the lack of an allergic response is used as an argument that this is all in the mind, and that they don’t have a problem with their gut physiology,” says Professor Guy Boeckxstaens, a gastroenterologist at KU Leuven and lead author of the new research. “With these new insights, we provide further evidence that we are dealing with a real disease.”

Histamine

His team’s laboratory and clinical studies reveal a mechanism that connects certain foods with activation of the cells that release histamine (called mast cells), and subsequent pain and discomfort. Earlier work by Professor Boeckxstaens and his colleagues showed that blocking histamine, an important component of the immune system, improves the condition of people with IBS.

In a healthy intestine, the immune system does not react to foods, so the first step was to find out what might cause this tolerance to break down. Since people with IBS often report that their symptoms began after a gastrointestinal infection, such as food poisoning, the researchers started with the idea that an infection while a particular food is present in the gut might sensitise the immune system to that food.

They infected mice with a stomach bug, and at the same time fed them ovalbumin, a protein found in egg white that is commonly used in experiments as a model food antigen. An antigen is any molecule that provokes an immune response. Once the infection cleared, the mice were given ovalbumin again, to see if their immune systems had become sensitised to it. The results were affirmative: the ovalbumin on its own provoked mast cell activation, histamine release, and digestive intolerance with increased abdominal pain. This was not the case in mice that had not been infected with the bug and received ovalbumin.

A spectrum of food-related immune diseases

The researchers were then able to unpick the series of events in the immune response that connected the ingestion of ovalbumin to activation of the mast cells. Significantly, this immune response only occurred in the part of the intestine infected by the disruptive bacteria. It did not produce more general symptoms of a food allergy.

Professor Boeckxstaens speculates that this points to a spectrum of food-related immune diseases. “At one end of the spectrum, the immune response to a food antigen is very local, as in IBS. At the other end of the spectrum is food allergy, comprising a generalised condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on.”

The researchers then went on to see if people with IBS reacted in the same way. When food antigens associated with IBS (gluten, wheat, soy and cow milk) were injected into the intestine wall of 12 IBS patients, they produced localised immune reactions similar to that seen in the mice. No reaction was seen in healthy volunteers.

The relatively small number of people involved means this finding needs further confirmation, but it appears significant when considered alongside the earlier clinical trial showing improvement during treatment of IBS patients with anti-histaminics. “This is further proof that the mechanism we have unravelled has clinical relevance,” Professor Boeckxstaens says.

A larger clinical trial of the antihistamine treatment is currently under way. “But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients,” he goes on. “Mast cells release many more compounds and mediators than just histamine, so if you can block the activation of these cells, I believe you will have a much more efficient therapy.”

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Materials provided by KU Leuven. Note: Content may be edited for style and length.

The study, published today (Wednesday) in the European Heart Journal [1], found that, compared to drinking no alcohol at all, just one alcoholic drink a day was linked to a 16% increased risk of atrial fibrillation over an average (median) follow-up time of nearly 14 years. This means that while four teetotallers in 100 might develop atrial fibrillation over the period of the study, five per 100 might develop the condition if they consumed alcohol starting with slightly more than an alcoholic drink a week and more than 75% of them consumed up to one drink a day [2]. The researchers categorised one alcoholic drink as containing 12 g of ethanol, which is the equivalent of a small (120 ml) glass of wine, a small beer (330 ml) or 40 ml of spirits.

It is well known that people who drink a lot of alcohol regularly are at increased risk of developing heart failure, and heart failure can increase the incidence of atrial fibrillation. Several studies have shown a slightly higher risk of heart problems for people who never drink alcohol; they often show that this risk reduces for people who drink a modest amount, and then rises sharply the more alcohol is consumed, creating a ‘J’ shape on graphs. Until now, it has not been clear whether this was also the case for atrial fibrillation.

However, in the current study led by Professor Renate Schnabel, a consultant cardiologist at the University Heart and Vascular Center, Hamburg-Eppendorf (Germany), researchers found that although low doses of alcohol were associated with a reduced risk of heart failure compared to teetotallers, a similar ‘J’ shape reduction in risk was not seen for atrial fibrillation. This suggests that the increased risk of atrial fibrillation among people drinking small amounts of alcohol was not triggered by heart failure.

Prof. Schnabel said: “To our knowledge, this is the largest study on alcohol consumption and long-term incidence of atrial fibrillation in the community. Previous studies have not had enough power to examine this question, although they have been able to show a relationship between alcohol intake and other heart and blood vessel problems, such as heart attack and heart failure. In our study, we can now demonstrate that even very low regular alcohol consumption may increase the risk of atrial fibrillation.

“These findings are important as the regular consumption of alcohol, the ‘one glass of wine a day’ to protect the heart, as is often recommended for instance in the lay press, should probably no longer be suggested without balancing risks and possible benefits for all heart and blood vessel diseases, including atrial fibrillation.”

The researchers analysed information on 107,845 people taking part in five community-based studies in Sweden, Norway, Finland, Denmark and Italy. The participants underwent medical examinations at the time they joined the studies between 1982 and 2010 and provided information on their medical histories, lifestyles (including alcohol and tobacco consumption), employment and education levels. A total of 100,092 participants did not have atrial fibrillation when they enrolled and their median age was nearly 48 years (range 24-97 years).

During the median follow-up period of nearly 14 years, 5,854 people developed atrial fibrillation. The associations between alcohol consumption and the risk of atrial fibrillation were similar for all types of alcoholic drinks and for men and women.

In addition to the 16% increased risk of atrial fibrillation compared to teetotallers seen in people who consumed only one alcoholic drink a day, the researchers found that the risk increased with increasing alcohol intake; up to two drinks a day was associated with a 28% increased risk and this went up to 47% for those who consumed more than four.

The exact mechanisms by which modest amounts of alcohol could trigger atrial fibrillation are not known. Studies have shown that heavy drinking over a short period of time can trigger ‘holiday heart syndrome’ in some people, and in some atrial fibrillation patients, small amounts of alcohol can trigger arrhythmia episodes.

Limitations of the study include the fact that study participants reported the type and quantity of alcohol they drank and this could lead to under-reporting; the information available did not enable the researchers to look at the effects of binge drinking; some episodes of atrial fibrillation can be asymptomatic and so may not have been reported; only adults across Europe were included in the analyses and so it may not be possible for the results to be generalised to other populations; as the study was observational, it can show only an association between alcohol intake and atrial fibrillation and not that alcohol causes atrial fibrillation.

In an accompanying editorial [3], Jorge A. Wong and David Conen from the Population Health Research Institute at McMaster University, Hamilton, Canada, write that the research “makes an important contribution to our understanding of the relationship between alcohol intake and incident AF, in particular at the lower spectrum of alcohol consumption. A significant relationship between alcohol and AF was identified, and even small quantities of alcohol were associated with an increased, albeit small, risk of incident AF.

“Together with a recent randomized trial showing that a reduction in alcohol intake led to a reduction in AF recurrence, these data suggest that lowering alcohol consumption may be important for both prevention and management of AF. Importantly, any reduction in low-to-moderate alcohol consumption to potentially prevent AF needs to be balanced with the potentially beneficial association low amounts of alcohol may have with respect to other cardiovascular outcomes . . . The net clinical benefit of consuming low amounts of alcohol requires further study, ideally in adequately powered randomized trials. Until then, each individual has to make its own best educated decision as to whether consuming up to one alcoholic drink per day is worthwhile and safe.”

Notes:

[1] “Alcohol consumption, cardiac biomarkers and risk of atrial fibrillation and adverse outcomes,” by Dora Csengeri et al. European Heart Journal. doi:10.1093/eurheartj/ehaa953

[2] Data on absolute risk are not given in the research paper. The absolute risk was calculated using further information from the researchers and the University of Cambridge Winton Centre for Risk and Evidence Communication RealRisk web tool: https://url.wintoncentre.uk/p6lcb

[3] “Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance,” by Jorge A. Wong and David Conen. European Heart Journal. doi:10.1093/eurheartj/ehaa955

The group, led by Lisa Beal, professor of ocean sciences at the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, provides a road map for an enhanced IndOOS to better meet the scientific and societal needs for more reliable environmental forecasts in the next decade. The 136 actionable recommendations from the three-year, internationally coordinated review were published in the Bulletin of the American Meteorological Society.

The scientists call for four major improvements to the current observing system:

1) more chemical and biological measurements in at-risk ecosystems and fisheries;

2) expansion into the western tropics to improve understanding of the monsoon;

3) better-resolved upper ocean processes to improve predictions of rainfall, drought, and heat waves; and

4) expansion into key coastal regions and the deep ocean to better constrain the basin-wide energy budget.

Although the smallest of the major oceans on Earth, the Indian Ocean is home to roughly one-third of the global population living among the 22 countries that border its rim. Many of these countries are developing or emerging economies vulnerable to climate changes such as sea level rise and more extreme weather events. The Indian Ocean also influences climate globally and is thought to have played a key role in regulating global mean surface temperatures.

The Indian Ocean Observing System, established in 2006, is a multinational network of sustained oceanic measurements that underpin understanding and forecasting of weather and climate for the Indian Ocean region and beyond. IndOOS is part of the Global Ocean Observing System (GOOS) which is coordinated through the World Meteorological Organization and the Intergovernmental Oceanographic Commission of the United Nations.

IndOOS-2 will require new agreements and partnerships with and among Indian Ocean rim countries, creating opportunities for them to enhance their monitoring and forecasting capacity, said the authors.

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Materials provided by University of Miami Rosenstiel School of Marine & Atmospheric Science. Original written by Diana Udel. Note: Content may be edited for style and length.