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Western diet may increase risk of gut inflammation, infection

Diet rich in sugar, fat damages immune cells in digestive tracts of mice

Washington University School of Medicine in St. Louis and Cleveland Clinic

Eating a Western diet impairs the immune system in the gut in ways that could increase risk of infection and inflammatory bowel disease, according to a study from researchers at Washington University School of Medicine in St. Louis and Cleveland Clinic.

The study, in mice and people, showed that a diet high in sugar and fat causes damage to Paneth cells, immune cells in the gut that help keep inflammation in check. When Paneth cells aren’t functioning properly, the gut immune system is excessively prone to inflammation, putting people at risk of inflammatory bowel disease and undermining effective control of disease-causing microbes. The findings, published May 18 in Cell Host & Microbe, open up new approaches to regulating gut immunity by restoring normal Paneth cell function.

“Inflammatory bowel disease has historically been a problem primarily in Western countries such as the U.S., but it’s becoming more common globally as more and more people adopt Western lifestyles,” said lead author Ta-Chiang Liu, MD, PhD, an associate professor of pathology & immunology at Washington University. “Our research showed that long-term consumption of a Western-style diet high in fat and sugar impairs the function of immune cells in the gut in ways that could promote inflammatory bowel disease or increase the risk of intestinal infections.”

Paneth cell impairment is a key feature of inflammatory bowel disease. For example, people with Crohn’s disease, a kind of inflammatory bowel disease characterized by abdominal pain, diarrhea, anemia and fatigue, often have Paneth cells that have stopped working.

Liu and senior author Thaddeus Stappenbeck, MD, PhD, chair of the Department of Inflammation and Immunity at Cleveland Clinic, set out to find the cause of Paneth cell dysfunction in people. They analyzed a database containing demographic and clinical data on 400 people, including an assessment of each person’s Paneth cells. The researchers found that high body mass index (BMI) was associated with Paneth cells that looked abnormal and unhealthy under a microscope. The higher a person’s BMI, the worse his or her Paneth cells looked. The association held for healthy adults and people with Crohn’s disease.

To better understand this connection, the researchers studied two strains of mice that are genetically predisposed to obesity. Such mice chronically overeat because they carry mutations that prevent them from feeling full even when fed a regular diet. To the researchers’ surprise, the obese mice had Paneth cells that looked normal.

In people, obesity is frequently the result of eating a diet rich in fat and sugar. So the scientists fed normal mice a diet in which 40% of the calories came from fat or sugar, similar to the typical Western diet. After two months on this chow, the mice had become obese and their Paneth cells looked decidedly abnormal.

“Obesity wasn’t the problem per se,” Liu said. “Eating too much of a healthy diet didn’t affect the Paneth cells. It was the high-fat, high-sugar diet that was the problem.”

The Paneth cells returned to normal when the mice were put back on a healthy mouse diet for four weeks. Whether people who habitually eat a Western diet can improve their gut immunity by changing their diet remains to be seen, Liu said.

“This was a short-term experiment, just eight weeks,” Liu said. “In people, obesity doesn’t occur overnight or even in eight weeks. People have a suboptimal lifestyle for 20, 30 years before they become obese. It’s possible that if you have Western diet for so long, you cross a point of no return and your Paneth cells don’t recover even if you change your diet. We’d need to do more research before we can say whether this process is reversible in people.”

Further experiments showed that a molecule known as deoxycholic acid, a secondary bile acid formed as a byproduct of the metabolism of gut bacteria, forms the link between a Western diet and Paneth cell dysfunction. The bile acid increases the activity of two immune molecules — farnesoid X receptor and type 1 interferon — that inhibit Paneth cell function.

Liu and colleagues now are investigating whether fat or sugar plays the primary role in impairing Paneth cells. They also have begun studying ways to restore normal Paneth cell function and improve gut immunity by targeting the bile acid or the two immune molecules.

Glutathione precursor gamma-glutamylcysteine may represent novel strategy for treatment and/or prevention of cognitive impairment

University of New South Wales(Australia), May 12, 2021

According to news originating from Sydney, Australia, research stated, “The accumulation of oxidative stress, neuroinflammation and abnormal aggregation of amyloid beta-peptide (A beta) have been shown to induce synaptic dysfunction and memory deficits in Alzheimer’s disease (AD). Cellular depletion of the major endogenous antioxidant Glutathione (GSH) has been linked to cognitive decline and the development of AD pathology.”

Our news journalists obtained a quote from the research from the University of New South Wales, “Supplementation with gamma-glutamylcysteine (gamma-GC), the immediate precursor and the limiting substrate for GSH biosynthesis, can transiently augment cellular GSH levels by bypassing the regulation of GSH homeostasis. In the present study, we investigated the effect of dietary supplementation of gamma-GC on oxidative stress and A beta pathology in the brains of APP/PS1 mice. The APP/PS1 mice were fed gamma-GC from 3 months of age with biomarkers of apoptosis and cell death, oxidative stress, neuroinflammation and A beta load being assessed at 6 months of age. Our data showed that supplementation with gamma-GC lowered the levels of brain lipid peroxidation, protein carbonyls and apoptosis, increased both total GSH and the glutathione/glutathione disulphide (GSH/GSSG) ratio and replenished ATP and the activities of the antioxidant enzymes (superoxide dismutase (SOD), catalase, glutamine synthetase and glutathione peroxidase (GPX)), the latter being a key regulator of ferroptosis. Brain A beta load was lower and acetylcholinesterase (AChE) activity was markedly improved compared to APP/PS1 mice fed a standard chow diet. Alteration in brain cytokine levels and matrix metalloproteinase enzymes MMP-2 and MMP-9 suggested that gamma-GC may lower inflammation and enhance A beta plaque clearance in vivo. Spatial memory was also improved by gamma-GC as determined using the Morris water maze.”

According to the news editors, the research concluded: “Our data collectively suggested that supplementation with gamma-GC may represent a novel strategy for the treatment and/or prevention of cognitive impairment and neurodegeneration.”

This research has been peer-reviewed.

Study led by NTU Singapore finds that microbes work as a network in causing lung infection

Nanyang Technological University (Singapore) May 21, 201

Traditionally, an infection is thought to happen when microbes – bacteria, fungi, or viruses – enter and multiply in the body, and its severity is associated with how prevalent the microbes are in the body.

Now, an international research team led by Nanyang Technological University, Singapore (NTU Singapore) has proposed a new way of understanding infections. Their study of close to 400 respiratory samples from patients with bronchiectasis, a chronic lung condition, has shown that microbes in the body exist as a network, and that an infection’s severity could be a result of interactions between these microbes.

Through statistical modelling of data from these respiratory samples, the scientists found that flare-ups of coughs and breathlessness (known as exacerbations) occurred more often when there were ‘negative interactions’ between communities of bacteria, viruses and fungi in the airways. A negative interaction occurs when the microbes compete rather than cooperate with one another.

These findings, published in one of the world’s leading scientific journals Nature Medicine in April, bring the scientists one step closer to developing a new way of tackling infections, by targeting microbial interactions rather than the specific microbes.

Assistant Professor Sanjay Haresh Chotirmall from the NTU Lee Kong Chian School of Medicine, who led the study, said: “Our current understanding of infections is that they occur when harmful microbes enter our bodies. This model of understanding, however, fails to account for resident microbes or explain why some patients with infection respond to antibiotics to which the microbe is resistant in laboratory testing. We are therefore proposing that microbes exist as networks, where interactions happen and that the resistant antibiotic in this case targets another microbe with which the culprit is interacting. We therefore can potentially improve clinical outcomes by breaking such crosstalk.

“The findings of our study are the first steps in providing a more holistic view of how infections occur. While our study looked at patients with bronchiectasis, we believe this concept applies to all forms of infection – whether skin, lung, or a gastrointestinal infection. This way of looking at infections potentially changes our understanding of infection and may offer fresh ways of treating them.”

Associate Professor John Abisheganaden, co-author of the study and Head of Department of Respiratory & Critical Care Medicine at Tan Tock Seng Hospital, said: “By applying an integrated and holistic method, this study provides a new and fresh approach to our understanding of respiratory infection. Applying this precision-medicine approach can help the managing physician better understand and choose the most appropriate antibiotic or other therapy to confer clinical benefit – in short, to guide us to the right treatment at the right time, and for the best outcome.”

Microbial interactions and infection

For their study, the scientists looked at patients with bronchiectasis, a disease of high Asian prevalence, where airways dilate irreversibly and, where infection promotes progression. Targeting bacteria with antibiotics reduces bacterial load and accompanying inflammation, which in turn alleviates symptoms and improves clinical outcomes.

To investigate interactions between microbes in the airways of patients with bronchiectasis, the team collected respiratory (sputum) samples from 383 patients from Singapore, Malaysia, Italy, and Scotland, including samples before, during and after bronchiectasis flare-ups.

After analysing the genetic material from bacteria, fungi and viruses in the samples, the scientists assessed for possible microbial interactions and found that patients with frequent flare-ups had more negative interactions, where microbes compete rather than cooperate, and that the number of such negative interactions increased even further during a flare-up. While changes to interactions between microbes during flare-ups was detected, there was surprisingly minimal change to the type and quantity of microbes present during a flare-up, and even after antibiotics were administered.

New treatment possibilities

The scientists believe that these findings suggest that microbial interactions potentially drive frequent flare-ups in patients.

Using these findings, the scientists have developed an online tool to help other researchers and physicians analyse microbial interactions in their own patient samples through the microbes’ genetic sequences.

Asst Prof Chotirmall, who is also NTU Provost’s Chair in Molecular Medicine, said: “We are proposing a fresh way to view infection, as networks rather than individual microbes. Targeting microbial interactions within an established network may promote more judicious antibiotic use and help curb rising antimicrobial resistance.”

The team is currently exploring the use of probiotics to treat bronchiectasis by regulating microbiomes within the air passages.

Pea flour helps malnourished children regain weight and restores gut flora

Imperial College London, May 21, 201

Adding pea flour to foods for severely malnourished children helps them gain weight and restores the balance of microbes in their gut.

In a small study of severely malnourished children in Uganda, researchers found that providing them with a mix containing cowpea flour improved their ability to absorb nutrients and gain weight, while maintaining their gut microbiome comparable to healthy children.

According to the researchers, the findings, published today in the journal Cell Reports Medicine, lay the foundations for larger trials with cowpea-based supplements and highlight the critical role of gut health in restoring nutrition in children with severe acute malnutrition.

Acute malnutrition is a major contributor to child mortality around the world. It remains a leading cause of death in children under five years of age and increases their risk of life-threatening events such as pneumonia, diarrheal disease or infections. Children with severe acute malnutrition can be treated with nutrient-rich, milk-based formulas to restore weight and nutrition, but despite treatment many will later go on to die.

Professor Gary Frost, head of the Center for Translational Nutrition and Food Research at Imperial College London, said: “These are children who have been admitted to hospital and often have other disease, such as bacterial sepsis, which complicates the picture—so they are very fragile.

“High quality feeds are lifesaving for many thousands of children. But sadly, when children are severely malnourished they can struggle to absorb nutrients and despite initial improvements in hospital, many remain very weak and will later go on to die.”

“We have been able to show that legume-enriched feeds are well tolerated by these very sick children, and they may also protect their ‘good’ gut microbes, compared to traditional feeds. Our hope is that this kind of intervention will help them to grow stronger by enabling their bodies to absorb more of the nutrients from the feed.”

More than ‘calories in’

Researchers at Imperial College London have been exploring the links between gut health and nutrition, with the aim of improving outcomes for severely malnourished children. Growing evidence suggests that gut microbes feed on carbohydrates from our diet, releasing nutrients which maintain the lining of the gut. Without this regular supply of nutrients, the gut lining deteriorates and becomes ‘leaky,” reducing our ability to absorb nutrients and increasing the risk of bugs entering the bloodstream where they can cause infection.

Previous research by the Imperial team has shown that increasing dietary fiber can help to overcome this ‘leaky gut’ syndrome and improve the absorption of nutrients, so they designed and tested a new feed fortified with cowpea—which contains a source of easily fermentable carbohydrates and fiber, both known to be key in maintaining gut health.

In a small proof of concept trial, researchers recruited 58 hospitalized children in Uganda with severe acute malnutrition to receive one of three feeds: a conventional feed; a feed containing the plant compound inulin; and a feed fortified with cowpea flour. Children in all three groups received antibiotics and other medical treatments, as needed, in addition to the feed.

Led by Ph.D. candidates Nuala Calder and Kevin Walsh, the team measured changes to weight after seven days of treatment, along with fecal sampling to look at changes to the makeup of their gut microbiome. The children were also followed up at 28 days.

The researchers found that overall, all feeds resulted in comparable weight gain after one week, and duration of hospital stay did not vary between groups. However, the cowpea feed limited the damage to gut microbes associated with antibiotic treatment—which can reduce the richness of the microbiome by killing off key groups of bugs. The same effect was not seen in conventional feeds or those enriched with inulin—a compound derived from plants—highlighting the role of fiber and other elements in the legume feed.

Following 28 days, there was limited difference in mortality between the groups, and sadly, despite treatment 12 children died (3, 6 and 3 from the respective groups). But analysis suggested that across the groups, children that died had higher levels of gut dysfunction and altered levels of short chain fatty acids, indicating reduced diversity of gut microbes.

Protecting gut bugs

Professor Frost said: “Our major finding was that the cowpea enriched feeds actually protect the gut bugs when these children are given antibiotics, so we know that the feed is actually helping the microbiota to survive some of the concurrent medical therapy these children are receiving.

“We also found that the children that died tended to have a worse gut problem than those who survived, so it has highlighted that the gut is very important in rescuing children from severe malnutrition. These legume enriched feeds may be a small step towards improving outcomes for those children.”

Professor Kathryn Maitland, Professor of Tropical Pediatric Infectious Disease at Imperial and based in Kenya, said: “This is a very small study, but it’s an important first step. The role the gut actively plays in the pathology of severe malnutrition has not been fully appreciated, and there are multiple parameters that need fixing. Fortifying feeds with legumes can go some way towards that. Many of these children may receive multiple antibiotics, which kills the microbiota, leaving only the microbes that are bad for human health, and these legume enriched feeds may actually help to resist that.”

Future trials are now planned to test the legume-enriched feeds in larger numbers of children with severe acute malnutrition in more regions. The team believes that if the feeds could be produced regionally, using legumes such as cowpea which can be grown and milled in East Africa, it could help to reduce the dependency on internationally produced feeds which may be more expensive and less effective.

Professor Maitland added: “Many feeds which are imported to East Africa are based on cow’s milk, or a dried form of it. They can contain a lot of sugars, such as sucrose and lactose, and these children can’t absorb this. In fact, quite a lot of these malnourished children may develop severe diarrhea from these feeds as they are lacking the enzymes to properly digest and absorb them, so our next steps are to tackle that as well.

“We think that the next iterations of our feed will include legumes, but will also not include any aspect of cow’s milk, replacing the sucrose with other carbohydrate sources. This also means that they can be produced locally.”

Professor Frost added: “We know that we can reverse the malnutrition, but this isn’t really fixing the whole problem. This approach is a radical change for these children. It’s taking a very different view of feeding. It’s not just about the nutrients flowing in, it’s about how compounds in plants are metabolized, and underlying gut health.”

Why blueberries are an effective weapon in the war against Alzheimer’s disease

 

University of Cincinnati,  May 21, 2021 

 

Could a plump, little blueberry really hold colossal promise in the fight against Alzheimer’s disease?  New research adds to the growing evidence that blueberries, bursting with antioxidants, could help diminish the devastating defects of dementia.

Blueberries are already known as a “super fruit,” thanks to their documented contribution to lowering the risk of heart disease and cancer. But now, newly released study findings show that certain flavonoids found in blueberries could also hold the key to lessening the effects of Alzheimer’s disease.

Over 5 million Americans suffer from Alzheimer’s disease, a number that is expected to continue to rise as the population ages. The Alzheimer’s Association estimates that as many as 7 million could fall prey to the disease by 2025, and that the number could triple by 2050.  In fact, Alzheimer’s has become the sixth leading cause of death in the United States, with one out of every three elderly persons dying of complications from Alzheimer’s or some other form of dementia.

 

But Alzheimer’s takes a toll on more than just human life. It is an extremely costly disease as well. Experts estimate that Alzheimer’s will cost the nation $236 million and that caregivers will spend more than $5,000 a year trying to care for their loved one.

Hope for Alzheimer’s disease patients: Blueberries found to improve cognition and memory

As scientists work to slow this alarming trend, researchers out of the University of Cincinnati Academic Health Center have released promising results of two human studies conducted in follow up to their earlier clinical trials. Lead author Robert Krikorian, Ph.D., stated that the new findings corroborate those from previous human and animal research.

The researchers, led by Krikorian, believe that blueberries’ beneficial effects against Alzheimer’s could be due to certain flavonoids found in the berries. Known as anthocyanins, they have been shown to improve cognition in tests with animals.

In one study, 47 adults, aged 68 and older, exhibiting mild cognitive impairment – a risk factor for Alzheimer’s disease – were given either freeze-dried blueberry powder or a placebo powder once a day for 16 weeks. The blueberry powder was equivalent to one cup of fresh blueberries.

 

Those receiving the blueberry powder were found to exhibit improved brain function and cognitive performance compared to those in the control group, with better memory and improved access to words and concepts.  In another study, 94 people, aged 62 to 80, were divided into four groups. The subjects did not have diagnosed early-onset Alzheimer’s, but did report feelings of having their memory decline.

In the trial, stated above (with 94 people), cognition was somewhat better for those consuming powder or fish oil only, but there was little improvement with memory. Also, researchers report that the MRI results were not as definitive for those receiving blueberry powder.

Even with somewhat less striking results from the second study, the scientists believe the two studies show that blueberries may be more effective in treating patients with cognitive impairments. Next up, the researchers want to conduct a study involving younger subjects, all with risk factors for Alzheimer’s.

Reaping the benefits of blueberries from your regular diet can be easy. Blueberries are an extremely popular berry and can be found in many stores (and farmers’ markets) throughout the world.  Naturally, to avoid excess consumption of chemicals, it’s best to eat organic varieties only.

As a matter of convenience and potency, the best way to incorporate blueberries into your diet is through a powder of pure (organic) blueberry extract or by eating whole, organic berries.  Baking or cooking blueberries will diminish the nutritional value of this powerful fruit.

Oxidative Stress, Vitamin D Deficiency and Male Infertility: An Under-Looked Aspect

Aga Khan University (Pakistan), May 21, 2021

Infertility is a known source of distress among couples worldwide. This agony significantly stems from the concern of not having an identifiable cause leading to infertility. With male factors accounting for 20-30% of the total causes of infertility (1), a thorough evaluation of both the partners is done.

Upon evaluation, Vitamin D deficiency was noticed significantly in males coming to infertility centres. However, its functions and how it impacted reproduction was not known until the research led to the discovery of Vitamin D Receptor (VDR) in many organs of the male reproductive tract. It is now known that vitamin D deficiency decreases male fertility by contributing to oxidative stress and gonadal insufficiency, disrupting spermatogenesis, affecting sperm morphology and normal calcium haemostasis. (2)

Oxidative stress, caused by an imbalance between oxidative and antioxidative mechanisms, is believed to be a well-known mechanism underlying idiopathic male infertility. Reproductive health professionals and researchers fittingly started searching for antioxidants to combat this imbalance. A study concluded that adding vitamin D to a cryopreserved semen sample reduced oxidative stress and resulted in better fertility outcomes (3). Animal trials have shown that Vitamin D supplementation reduced oxidative stress and improved semen DNA integrity (4).

As Vitamin D exerts its effects by binding to Vitamin D receptors, it was noted that vitamin D receptor null mutant mice had a significant reduction in successful reproductive outcomes due to gonadal insufficiencies. Reduced levels of oestrogen and testosterone were seen along with low sperm count, reduced motility, abnormal spermatogenesis and histological abnormalities in testes of mutant mice. These insufficiencies were attributed to a decreased CYP2R1, CYP27B1 and CYP24A1 expression, lower aromatase activity, secondary to suppression of CYP19 gene and calcium supplementation improved fertility in such cases. (5)

There is limited human data available on how Vitamin D deficiency causes gonadal insufficiency, which is important to maintain normal reproductive physiology. More studied are needed to clarify the role of vitamin D in gonadal physiology. Considering the importance of Vitamin D on reproductive functions, its role in causing Oxidative stress and gonadal dysfunction, we suggest randomized control trials in pre-pubertal phase.

Want to escape Alzheimer’s disease? Run for your life and exercise

Tel Aviv Sourasky Medical Center (Israel), May 20, 2021

Exercise slows down aging of the brain and can reduce risks of Alzheimer’s disease and other dementias by about half.

There is a growing amount of medical evidence that exercise slows down the aging of the brain and can reduce the risk of Alzheimer’s disease and other dementias by about half, according to Prof. Nir Giladi, chief of neurology at Tel Aviv Sourasky Medical Center.

He said that the modern sedentary way of life reduces the amount of body movement. Long-term epidemiological and physical studies show that exercise can improve memory, concentration and mood and minimize pain, as well as reduce the risk of cognitive damage, stroke, Parkinson’s disease and depression.

The connection between exercise and brain function was first disclosed from animal studies two decades ago, said Giladi. Brains of rats that ran on a wheel for three months at a time had many more neurons and synapses through which electric signals connect. Exercise causes these to multiply, said Giladi.

“These findings flew in the face of the belief that over the age of 30, the neurons decline irreversibly. Today we know that the adult brain has many stem cells that when stimulated can differentiate and turn into ripe neurons that know how to create synapses.” The neurologist added that for some unknown reason, the best potential for differentiation exists in brain regions responsible for memory.

Exercise promotes the secretion of trophic factors — including brain-derived neurotrophic factor that encourage the growth of stem cells that turn into adult nerve cells. he added. These factors activate genes responsible for the development of stem cells in the hippocampus and other brain regions involved in memory, storage and processing of data. They are available in large quantities during a baby’s first years when the brain develops at a rapid pace, but the amounts decline during adolescence and aging.

The greater the amount, the more the brain grows and holds more nerve cells, especially in the hippocampus, he said. Exerting the muscles activates unique genes that encourage the muscle cells and apparently others to create proteins that increase the synthesis of trophic factors. “This is why those who exercise regularly look and have younger brain function — and their cells are more protected from diseases, trauma and natural aging.”

Giladi said it was best to do aerobic exercise (causing the heart and lungs to exert themselves) along with non-aerobic exercise (strengthening the muscles on the skeleton) at least three times a week. Even if you exercise just as an adult and the cognitive decline has begun, your physical activity will slow down the rate of decline.

A study published in the journal PNAS  using MRI to see the effect of regular exercise on the brain showed that the brains of healthy 75-year-olds who performed physical activity at least three times a week declined slower in the regions of memory, concentration, planning, initiative and management abilities. The same thing was noted in studies of teenagers, Giladi said. Exercise influences the brain cell in deciding which genes will function and contribute to this and which will be neutralized. This is thus epigenetics, in which the environment actually affects the genes, the neurologist said.

Exercise also increases the supply of blood to the organs, including the brain, he continued, and encourages the growth of alternate blood vessels to take over functions from clogged vessels.

He bemoaned the fact that many Israelis don’t exercise regularly. An average of 150 to 300 minutes per week — half aerobic and half non-aerobic — can improve the abilities of the brain and protect it from disease, Giladi concluded.