Coffee lovers, rejoice! Drinking more coffee associated with decreased heart failure risk

Circulation: Heart Failure Journal Report

February 9, 2021

Science Daily/American Heart Association

Dietary information from three large, well-known heart disease studies suggests drinking one or more cups of caffeinated coffee may reduce heart failure risk, according to research published today in Circulation: Heart Failure, an American Heart Association journal.

Coronary artery disease, heart failure and stroke are among the top causes of death from heart disease in the U.S. "While smoking, age and high blood pressure are among the most well-known heart disease risk factors, unidentified risk factors for heart disease remain," according to David P. Kao, M.D., senior author of the study, assistant professor of cardiology and medical director at the Colorado Center for Personalized Medicine at the University of Colorado School of Medicine in Aurora, Colorado.

"The risks and benefits of drinking coffee have been topics of ongoing scientific interest due to the popularity and frequency of consumption worldwide," said Linda Van Horn, Ph.D., R.D., professor and Chief of the Department of Preventive Medicine's Nutrition Division at the Northwestern University Feinberg School of Medicine in Chicago, and member of the American Heart Association's Nutrition Committee. "Studies reporting associations with outcomes remain relatively limited due to inconsistencies in diet assessment and analytical methodologies, as well as inherent problems with self-reported dietary intake."

Kao and colleagues used machine learning through the American Heart Association's Precision Medicine Platform to examine data from the original cohort of the Framingham Heart Study and referenced it against data from both the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study to help confirm their findings. Each study included at least 10 years of follow-up, and, collectively, the studies provided information on more than 21,000 U.S. adult participants.

To analyze the outcomes of drinking caffeinated coffee, researchers categorized consumption as 0 cups per day, 1 cup per day, 2 cups per day and ?3 cups per day. Across the three studies, coffee consumption was self-reported, and no standard unit of measure were available.

The analysis revealed:

• In all three studies, people who reported drinking one or more cups of caffeinated coffee had an associated decreased long-term heart failure risk.

• In the Framingham Heart and the Cardiovascular Health studies, the risk of heart failure over the course of decades decreased by 5-to-12% per cup per day of coffee, compared with no coffee consumption.

• In the Atherosclerosis Risk in Communities Study, the risk of heart failure did not change between 0 to 1 cup per day of coffee; however, it was about 30% lower in people who drank at least 2 cups a day.

• Drinking decaffeinated coffee appeared to have an opposite effect on heart failure risk -- significantly increasing the risk of heart failure in the Framingham Heart Study. In the Cardiovascular Health Study however; there was no increase or decrease in risk of heart failure associated with drinking decaffeinated coffee. When the researchers examined this further, they found caffeine consumption from any source appeared to be associated with decreased heart failure risk, and caffeine was at least part of the reason for the apparent benefit from drinking more coffee.

"The association between caffeine and heart failure risk reduction was surprising. Coffee and caffeine are often considered by the general population to be 'bad' for the heart because people associate them with palpitations, high blood pressure, etc. The consistent relationship between increasing caffeine consumption and decreasing heart failure risk turns that assumption on its head," Kao said. "However, there is not yet enough clear evidence to recommend increasing coffee consumption to decrease risk of heart disease with the same strength and certainty as stopping smoking, losing weight or exercising."

According to the federal dietary guidelines, three to five 8-ounce cups of coffee per day can be part of a healthy diet, but that only refers to plain black coffee. The American Heart Association warns that popular coffee-based drinks such as lattes and macchiatos are often high in calories, added sugar and fat. In addition, despite its benefits, research has shown that caffeine also can be dangerous if consumed in excess. Additionally, children should avoid caffeine. The American Academy of Pediatrics recommends that, in general, kids avoid beverages with caffeine.

"While unable to prove causality, it is intriguing that these three studies suggest that drinking coffee is associated with a decreased risk of heart failure and that coffee can be part of a healthy dietary pattern if consumed plain, without added sugar and high fat dairy products such as cream," said Penny M. Kris-Etherton, Ph.D., R.D.N., immediate past chairperson of the American Heart Association's Lifestyle and Cardiometabolic Health Council Leadership Committee, Evan Pugh University Professor of Nutritional Sciences and distinguished professor of nutrition at The Pennsylvania State University, College of Health and Human Development in University Park. "The bottom line: enjoy coffee in moderation as part of an overall heart-healthy dietary pattern that meets recommendations for fruits and vegetables, whole grains, low-fat/non-fat dairy products, and that also is low in sodium, saturated fat and added sugars. Also, it is important to be mindful that caffeine is a stimulant and consuming too much may be problematic -- causing jitteriness and sleep problems."

Study limitations that may have impacted the results of the analysis included differences in the way coffee drinking was recorded and the type of coffee consumed. For example, drip, percolated, French press or espresso coffee types; origin of the coffee beans; and filtered or unfiltered coffee were details not specified. There also may have been variability regarding the unit measurement for 1 cup of coffee (i.e., how many ounces per cup). These factors could result in different caffeine levels. In addition, researchers caution that the original studies detailed only caffeinated or decaffeinated coffee, therefore these findings may not apply to energy drinks, caffeinated teas, soda and other food items with caffeine including chocolate.

https://www.sciencedaily.com/releases/2021/02/210209083513.htm

Fungi in the gut prime immunity against infection

February 5, 2021

Science Daily/Weill Cornell Medicine

Common fungi, often present in the gut, teach the immune system how to respond to their more dangerous relatives, according to new research from scientists at Weill Cornell Medicine. Breakdowns in this process can leave people susceptible to deadly fungal infections.

The study, published Feb. 5 in Cell, reveals a new twist in the complex relationship between humans and their associated microbes, and points the way toward novel therapies that could help combat a rising tide of drug-resistant pathogens.

The new discovery stemmed from work on inflammatory bowel disease, which often causes patients to carry larger than normal populations of fungi in their guts. These patients often develop strong antibody responses against mannan, a molecule common to a wide range of fungal species. However, Dr. Iliyan Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine, noticed that healthy controls in these studies also had some level of anti-fungal antibodies. "There was no actual evidence for fungal infections in the healthy individuals that we examined, so we started thinking about the possible function of those antibodies," said Dr. Iliev, who is senior author on the study and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease.

The team developed a platform that allowed them to determine which gut fungi are targeted by antibodies in the blood of individual patients. They detected a strong response against the yeast Candida albicans. Turning to experiments in mice, Dr. Iliev and Itai Doron, a Weill Cornell Medicine Graduate School of Medical Sciences doctoral candidate in the lab and lead author on the study, found that colonizing the animals' guts with Candida albicans caused them to develop antibodies against the fungus in their bloodstreams, even though they didn't develop blood-borne fungal infections. Instead, the animals' immune cells appeared to transport fungal antigens to the spleen, stimulating the production of circulating antibodies in the bloodstream. "Those fungi just educate that immune response," Dr. Iliev said.

Iliev and his colleagues mimicked this process by treating mice with immunosuppressive drugs. When a Candida species colonizes the gut of these mice, the fungus moves into the bloodstream, causing a fatal infection. Treating the mice with purified anti-fungal antibodies from donor animals protected the immunosuppressed mice from these infections. The same strategy worked against infection with either Candida albicans or the emerging pathogenic yeast Candida auris, which has become a major cause of fungal disease in immunosuppressed patients and the elderly in recent years.

Collaborating with researchers at INSERM in Paris, France, the Weill Cornell Medicine team also looked at serum from patients with mutations in a gene called CARD9. This mutation affects a critical adapter protein in the immune system, leaving the affected individuals susceptible to severe fungal infections. Dr. Iliev's team found that the serum of these patients lacked the anti-fungal antibodies normally seen in serum of patients without this mutation. Experiments in mice confirmed an essential and specific role for CARD9 in priming the production of anti-fungal antibodies.

Graphic depicting relationship between fungi in gut, antibody levels and CARD gene Relationship between gut fungi, anti-fungal antibodies, CARD9 gene, and fungal immunity. Image courtesy of the Iliev lab.

The results suggest that normal intestinal fungi such as Candida albicans may function as a kind of intestinal vaccine against fungal infection in healthy people, by inducing the production of bloodborne antibodies that can target multiple species of potentially pathogenic fungi. When those fungi do enter the bloodstream, the antibodies bind them and target them for destruction by cells of the immune system. In patients with suppressed immunity, the anti-fungal antibodies may decline, leaving them vulnerable to fungal infection. New therapies that involve either stimulating the production of anti-fungal antibodies, or injecting such purified antibodies directly into patients' bloodstreams, could potentially help combat these increasingly common infections.

If that approach works, it would be a welcome development. "Many fungal infections in immunosuppressed patients and elderly patients are happening by translocation of pathogenic Candida species from the gastrointestinal tract, and the survival rates upon systemic spreading are alarmingly low," said Dr. Iliev.

https://www.sciencedaily.com/releases/2021/02/210205155813.htm

How air pollution may increase the risk of cardiovascular disease

Fine particulate air pollution stimulates production of inflammatory cells, leading to inflammation of the arteries

February 4, 2021

Science Daily/Massachusetts General Hospital

Tiny particles of air pollution -- called fine particulate matter -- can have a range of effects on health, and exposure to high levels is a known risk factor for cardiovascular disease. New research led by investigators at Massachusetts General Hospital (MGH) reveals that fine particulate matter has a detrimental impact on cardiovascular health by activating the production of inflammatory cells in the bone marrow, ultimately leading to inflammation of the arteries. The findings are published in the European Heart Journal.

The retrospective study included 503 patients without cardiovascular disease or cancer who had undergone imaging tests at MGH for various medical reasons. The scientists estimated participants' annual average fine particulate matter levels using data obtained from the U.S. Environment Protection Agency's air quality monitors located closest to each participant's residential address.

Over a median follow-up of 4.1 years, 40 individuals experienced major cardiovascular events, such as heart attacks and strokes, with the highest risk seen in participants with higher levels of fine particulate matter at their home address. Their risk was elevated even after accounting for cardiovascular risk factors, socioeconomic factors, and other key confounders. Imaging tests assessing the state of internal organs and tissues showed that these participants also had higher bone marrow activity, indicating a heightened production of inflammatory cells (a process called leukopoiesis), and elevated inflammation of the arteries. Additional analyses revealed that leukopoiesis in response to air pollution exposure is a trigger that causes arterial inflammation.

"The pathway linking air pollution exposure to cardiovascular events through higher bone marrow activity and arterial inflammation accounted for 29% of the relationship between air pollution and cardiovascular disease events," says co-first author Shady Abohashem, MD, a cardiovascular imaging fellow at MGH. "These findings implicate air pollution exposure as an underrecognized risk factor for cardiovascular disease and suggest therapeutic targets beyond pollution mitigation to lessen the cardiovascular impact of air pollution exposure."

Co-first author Michael Osborne, MD, a cardiologist at MGH, explains that therapies targeting increased inflammation following exposure to fine particulate matter may benefit patients who cannot avoid air pollution. "Importantly, most of the population studied had air pollution exposures well below the unhealthy thresholds established by the World Health Organization, suggesting that no level of air pollution can truly be considered safe," he says.

https://www.sciencedaily.com/releases/2021/02/210204135742.htm

Alcohol consumption linked to portion of cancer incidence and mortality

Findings call for implementation of policies and cancer control efforts to reduce alcohol consumption

January 19, 2021

Science Daily/American Cancer Society

A new study finds that alcohol consumption accounts for a considerable portion of cancer incidence and mortality in all 50 states and the District of Columbia. The article, which appears in Cancer Epidemiology, states that the proportion of cancer cases attributable to alcohol consumption ranged from a high of 6.7% in Delaware to a low of 2.9% in Utah. Similarly, Delaware had the highest proportion of alcohol-related cancer deaths (4.5%) and Utah had the lowest (1.9%).

This study conducted by Farhad Islami, MD, PhD, and colleagues at the American Cancer Society is the first to estimate contemporary proportions and counts of alcohol-attributable cancer cases and deaths for all states. Data shows the proportions were generally higher in New England and Western states and lower in Midwestern and Southern states.

"This information is important for prioritizing state-level cancer prevention and control efforts to reduce alcohol consumption and the burden of alcohol-related cancers," said Dr. Islami.

The proportion of alcohol-related cancers was far greater for some individual cancer types. For oral cavity/pharyngeal cancer cases, for example, it ranged from 36% in Utah to 62.5% in Delaware and was 45% or more in 45 states and the District of Columbia. By sex, alcohol-related cancer cases and deaths for most evaluated cancer types were higher among men, in part reflecting higher levels of alcohol consumption among men.

In the U.S. on average, alcohol consumption accounted for 4.8% of cancer cases and 3.2% of cancer deaths, or about 75,200 cancer cases and 18,950 cancer deaths annually, during 2013 to 2016.

In addition, the authors say, "healthcare providers and public health practitioners can educate the community to expand the currently limited awareness of the cancer-related risks of alcohol consumption." The American Cancer Society's guideline for Diet and Physical Activity for Cancer Prevention states that it is best not to consume alcohol; for those who do drink, consumption should be limited to no more than 1 drink per day for women and 2 drinks per day for men.

https://www.sciencedaily.com/releases/2021/01/210119114255.htm

One small alcoholic drink a day is linked to an increased risk of atrial fibrillation

January 17, 2021

Science Daily/European Society of Cardiology

A study of nearly 108,000 people has found that people who regularly drink a modest amount of alcohol are at increased risk of atrial fibrillation, a condition where the heart beats in an abnormal rhythm.

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."

https://www.sciencedaily.com/releases/2021/01/210117132231.htm

Poor gut health connected to severe COVID-19

January 12, 2021

Science Daily/American Society for Microbiology

People infected with COVID-19 experience a wide range of symptoms and severities, the most commonly reported including high fevers and respiratory problems. However, autopsy and other studies have also revealed that the infection can affect the liver, kidney, heart, spleen -- and even the gastrointestinal tract. A sizeable fraction of patients hospitalized with breathing problems also have diarrhea, nausea and vomiting, suggesting that when the virus does get involved in the GI tract it increases the severity of the disease.

In a review published this week in mBio, microbiologist Heenam Stanley Kim, Ph.D, from Korea University's Laboratory for Human-Microbial Interactions, in Seoul, examined emerging evidence suggesting that poor gut health adversely affects COVID-19 prognosis. Based on his analysis, Kim proposed that gut dysfunction -- and its associated leaky gut -- may exacerbate the severity of infection by enabling the virus to access the surface of the digestive tract and internal organs. These organs are vulnerable to infection because they have widespread ACE2 -- a protein target of SARS-CoV-2 -- on the surface.

"There seems to be a clear connection between the altered gut microbiome and severe COVID-19," Kim said.

Studies have demonstrated that people with underlying medical conditions including high blood pressure, diabetes and obesity face a higher risk of severe COVID-19. Risk also increases with age, with older adults most vulnerable to the most serious complications and likelihood of hospitalization. But both of these factors -- advanced age and chronic conditions -- have a well-known association with an altered gut microbiota. This imbalance can affect gut barrier integrity, Kim noted, which can allow pathogens and pathobionts easier access to cells in the intestinal lining.

So far, the link between gut health and COVID-19 prognosis hasn't been empirically demonstrated, Kim noted. Some researchers have argued, he said, that unhealthy gut microbiomes may be an underlying reason for why some people have such severe infections.

What studies have been done hint at a complicated relationship. A study on symptomatic COVID-19 patients in Singapore, for example, found that about half had a detectable level of the coronavirus in fecal tests -- but only about half of those experienced GI symptoms. That study suggests that even if SARS-CoV-2 reaches the GI tract, it may not cause problems. Kim also noted that a person's gut health at the time of infection may be critical for symptom development.

Many recent studies have found reduced bacterial diversity in gut samples collected from COVID-19 patients, compared to samples from healthy people. The disease has also been linked to a depletion of beneficial bacterial species -- and the enrichment of pathogenic ones. A similar imbalance has been associated with influenza A infection, though the 2 viruses differ in how they change the overall microbial composition.

The depleted bacterial species associated with COVID-19 infection include some families that are responsible for producing butyrate, a short-chain fatty acid, which plays a pivotal role in gut health by reinforcing gut-barrier function.

Kim said he started analyzing the studies after realizing that wealthy countries with a good medical infrastructure -- including the United States and nations in Western Europe -- were among the hardest hit by the virus. The "western diet" that's common in these countries is low in fiber, and "a fiber-deficient diet is one of the main causes of altered gut microbiomes," he said, "and such gut microbiome dysbiosis leads to chronic diseases."

The pathogenesis of COVID-19 is still not fully understood. If future studies do show that gut health affects COVID-19 prognosis, Kim argued, then clinicians and researchers should exploit that connection for better strategies aimed at preventing and managing the disease. Eating more fiber, he said, may lower a person's risk of serious disease. And fecal microbiota transplantation might be a treatment worth considering for patients with the worst cases of COVID-19.

The problem with gut health goes beyond COVID-19, though, he said. Once the pandemic passes, the world will still have to reckon with chronic diseases and other problems associated with poor gut health.

"The whole world is suffering from this COVID-19 pandemic," Kim said, "but what people do not realize is that the pandemic of damaged gut microbiomes is far more serious now."

https://www.sciencedaily.com/releases/2021/01/210112085347.htm

Higher coffee intake may be linked to lower prostate cancer risk

Each additional daily cup associated with reduction in risk of nearly 1%

January 11, 2021

Science Daily/BMJ

Drinking several cups of coffee every day may be linked to a lower risk of developing prostate cancer, suggests a pooled data analysis of the available evidence, published in the online journal BMJ Open.

Each additional daily cup of the brew was associated with a reduction in relative risk of nearly 1%, the findings indicate.

Prostate cancer is the second most common cancer, and the sixth leading cause of cancer death in men. Nearly three out of four cases occur in the developed world, and since the 1970s, new cases of the disease have risen sharply in Asian countries, including Japan, Singapore, and China.

Coffee consumption has been linked to a lower relative risk of liver, bowel, and breast cancers, but as yet, there is no conclusive evidence for its potential role in prostate cancer risk reduction.

In a bid to advance understanding of the issue, the researchers trawled research databases for relevant cohort studies published up to September 2020.

They pooled the data from 16: 15 reported on the risk of prostate cancer associated with the highest, compared with the lowest, coffee consumption; 13 reported on the risk associated with an additional daily cup. The highest level of consumption ranged from 2 to 9 or more cups a day; the lowest level ranged from none to fewer than 2 cups a day.

The included studies were carried out in North America (7), Europe (7) and Japan (2). They included more than 1 million men (1,081, 586) of whom 57,732 developed prostate cancer.

Compared with the lowest category of coffee consumption, the highest category was associated with a reduction in prostate cancer risk of 9%. And each additional daily cup was associated with a reduction in risk of 1%.

Further refining the analysis to localised and advanced prostate cancer, showed that compared with the lowest intake, the highest intake was associated with a 7% lower risk of localised prostate cancer, and a 12%-16% lower risk for advanced and fatal prostate cancer, respectively.

The researchers acknowledge that because of the observational design of the included cohort studies, unmeasured or uncontrolled factors in the original studies may have skewed the pooled risk estimate.

The amount of coffee drunk may also have been misclassified as it depended on recall. And the type of coffee and brewing methods varied among the studies. The design and methods of the included studies also varied, so caution in interpreting the findings is warranted, they say.

Nevertheless, there are plausible biological explanations for their findings, they highlight.

Coffee improves glucose metabolism, has anti-inflammatory and antioxidant effects, and affects sex hormone levels, all of which may influence the initiation, development and progression of prostate cancer, they point out.

And they conclude: "This study suggests that increased coffee consumption may be associated with a reduced risk of prostate cancer. Further research is still warranted to explore the underlying mechanisms and active compounds in coffee.

"If the association is further proved to be a causal effect, men might be encouraged to increase their coffee consumption to potentially decrease the risk of prostate cancer."

https://www.sciencedaily.com/releases/2021/01/210111190137.htm

Make-up of gut microbiome may influence COVID-19 severity and immune response

Imbalances in type and volume of bacteria may also be implicated in 'long COVID'

January 11, 2021

Science Daily/BMJ

The variety and volume of bacteria in the gut, known as the microbiome, may influence the severity of COVID-19 as well as the magnitude of the immune system response to the infection, suggests research published online in the journal Gut.

Imbalances in the make-up of the microbiome may also be implicated in persisting inflammatory symptoms, dubbed 'long COVID', the findings suggest.

COVID-19 is primarily a respiratory illness, but the evidence suggests that the gut may also have a role.

As the gut is the largest immunological organ in the body and its resident microbes are known to influence immune responses, the researchers wanted to find out if the gut microbiome might also affect the immune system response to COVID-19 infection.

They therefore obtained blood and stool samples and medical records from 100 hospital inpatients with laboratory-confirmed COVID-19 infection between February and May 2020 and from 78 people without COVID-19 who were taking part in a microbiome study before the pandemic.

The severity of COVID-19 was classified as mild in the absence of x-ray evidence of pneumonia; moderate if pneumonia with fever and respiratory tract symptoms were detected; severe if patients found it very difficult to breathe normally; and critical if they needed mechanical ventilation or experienced organ failure requiring intensive care.

To characterise the gut microbiome, 41 of the COVID patients provided multiple stool samples while in hospital, 27 of whom provided serial stool samples up to 30 days after clearance of SARS-CoV-2, the virus responsible for COVID-19.

Analysis of all 274 stool samples showed that the make-up of the gut microbiome differed significantly between patients with and without COVID-19, irrespective of whether they had been treated with drugs, including antibiotics.

COVID patients had higher numbers of Ruminococcus gnavus, Ruminococcus torques and Bacteroides dorei species than people without the infection.

And they had far fewer of the species that can influence immune system response, such as Bifidobacterium adolescentis, Faecalibacterium prausnitzii and Eubacterium rectale.

Lower numbers of F. prausnitzii and Bifidobacterium bifidum were particularly associated with infection severity after taking account of antibiotic use and patient age.

And the numbers of these bacteria remained low in the samples collected up to 30 days after infected patients had cleared the virus from their bodies.

COVID-19 infection prompts the immune system to produce inflammatory cytokines in response. In some cases, this response can be excessive ('cytokine storm'), causing widespread tissue damage, septic shock, and multiorgan failure.

Analysis of the blood samples showed that the microbial imbalance found in the COVID patients was also associated with raised levels of inflammatory cytokines and blood markers of tissue damage, such as C-reactive protein and certain enzymes.

This suggests that the gut microbiome might influence the immune system response to COVID-19 infection and potentially affect disease severity and outcome, say the researchers.

"In light of reports that a subset of recovered patients with COVID-19 experience persistent symptoms, such as fatigue, dyspnoea [breathlessness] and joint pains, some over 80 days after initial onset of symptoms, we posit that the dysbiotic gut microbiome could contribute to immune-related health problems post-COVID-19," they write.

This is an observational study, and as such, can't establish cause, added to which the gut microbiome varies widely among different populations, so the changes observed in this study may not be applicable to other COVID patients elsewhere, caution the researchers.

But they point to mounting evidence showing that gut microbes are linked to inflammatory diseases within and beyond the gut.

And they conclude: "Bolstering of beneficial gut species depleted in COVID-19 could serve as a novel avenue to mitigate severe disease, underscoring the importance of managing patients' gut microbiota during and after COVID-19."

https://www.sciencedaily.com/releases/2021/01/210111190135.htm

Link between gut microbes, diet and illnesses

January 11, 2021

Science Daily/King's College London

Diets rich in healthy and plant-based foods encourages the presence of gut microbes that are linked to a lower risk of common illnesses including heart disease, research has found.

A large-scale international study using metagenomics and blood chemical profiling has uncovered a panel of 15 gut microbes associated with lower risks of common conditions such as obesity and type 2 diabetes. The study has been published today in Nature Medicine from researchers at King's College London, Massachusetts General Hospital (MGH), Harvard T.H. Chan School of Public Health, the University of Trento, Italy, and health start-up company ZOE.

The PREDICT 1 (Personalized Responses to Dietary Composition Trial 1) analyzed detailed data on the composition of participants' gut microbiomes, their dietary habits, and cardiometabolic blood biomarkers. It uncovered strong links between a person's diet, the microbes in their gut (microbiome) and their health.

Researchers identified microbes that positively or negatively correlate 'good' and 'bad' with an individual's risk of certain serious conditions such as diabetes, heart disease and obesity. Surprisingly, the microbiome has a greater association to these markers than other factors, such as genetics. Some of the identified microbes are so novel that they have not yet been named.

The researchers defined a "healthy" diet as one that contained a mix of foods associated with a lower risk of chronic disease. They found that trial subjects who ate such a diet, or one rich in plants, were more likely to have high levels of specific 'good' gut microbes which are associated with a low risk of common illnesses. The researchers also found microbiome-based biomarkers of obesity as well as markers for cardiovascular disease and impaired glucose tolerance, which are key risk factors for COVID. These findings can be used to help create personalized eating plans designed specifically to improve one's health.

Dr. Sarah Berry, Reader in Nutrition Sciences at King's College London said, "As a nutritional scientist, finding novel microbes that are linked to specific foods, as well as metabolic health, is exciting. Given the highly personalised composition of each individuals' microbiome, our research suggests that we may be able to modify our gut microbiome to optimize our health by choosing the best foods for our unique biology."

For example, the findings reveal that having a microbiome rich in Prevotella copri and Blastocystis species was associated with maintaining a favorable blood sugar level after a meal. Other species were linked to lower post-meal levels of blood fats and markers of inflammation.

Professor Tim Spector, Epidemiologist from King's College London, who started the PREDICT study program and is scientific founder of ZO, said: "When you eat, you're not just nourishing your body, you're feeding the trillions of microbes that live inside your gut."

Nicola Segata, PhD, professor and principal investigator of the Computational Metagenomics Lab at the University of Trento, Italy and leader of the microbiome analysis in the study, said: "We were surprised to see such large, clear groups of what we informally call 'good' and 'bad' microbes emerging from our analysis. It is also exciting to see that microbiologists know so little about many of these microbes that they are not even named yet. This is now a big area of focus for us, as we believe they may open new insights in the future into how we could use the gut microbiome as a modifiable target to improve human metabolism and health."

https://www.sciencedaily.com/releases/2021/01/210111112208.htm

Turning on the switch for plasticity in the human brain

January 29, 2021

Science Daily/Marine Biological Laboratory

The most powerful substance in the human brain for neuronal communication is glutamate. It is by far the most abundant, and it's implicated in all kinds of operations. Among the most amazing is the slow restructuring of neural networks due to learning and memory acquisition, a process called synaptic plasticity. Glutamate is also of deep clinical interest: After stroke or brain injury and in neurodegenerative disease, glutamate can accumulate to toxic levels outside of neurons and damage or kill them.

Shigeki Watanabe of Johns Hopkins University School of Medicine, a familiar face at the Marine Biological Laboratory (MBL) as a faculty member and researcher, is hot on the trail of describing how glutamate signaling works in the brain to enable neuronal communication. In a paper last fall, Watanabe (along with several MBL Neurobiology course students) described how glutamate is released from neural synapses after the neuron fires. And today, Watanabe published a follow-up study in Nature Communications.

"With this paper, we uncover how signals are transmitted across synapses to turn on the switch for plasticity," Watanabe says. "We demonstrate that glutamate is first released near AMPA-type glutamate receptors, to relay the signal from one neuron to the next, and then near NMDA-type receptors immediately after the first signal to activate the switch for synaptic plasticity."

This new study was also partly conducted in the MBL Neurobiology course, where Watanabe is a faculty member. "It began in 2018 with (course students) Raul Ramos and Hanieh Falahati, and then we followed up in 2019 with Stephen Alexander Lee and Christine Prater. Shuo Li, the first author, was my teaching assistant for the Neurobiology course for both years," Watanabe says. He will be returning to the MBL this summer to teach in the course -- and discover more.

https://www.sciencedaily.com/releases/2021/01/210129153753.htm