Sat. Aug 17th, 2019

265 CNO TECHNICAL NEWSLETTER FOR STAFF

33 min read

265 CNO STAFF TEST 23 JUL 2019

In This Issue:

  1. ‘Good’ bacteria may prevent — and reverse — food allergy
  2. Discovery of performance-enhancing bacteria in the human microbiome
  3. Could coffee be the secret to fighting obesity?
  4. Study finds micronutrient deficiencies common at time of celiac disease diagnosis
  5. Cannabidiol is a powerful new antibiotic
  6. Plant-based diet leads to Crohn’s Disease remission, according to case study
  7. Study: Phenols in cocoa bean shells may reverse obesity-related problems in mouse cells
  8. Processed foods may hold key to rise in autism
  9. Goat milk formula could benefit infant gut health: Study
  10. Low-carb ‘keto’ diet (‘Atkins-style’) may modestly improve cognition in older adults
  11. Research shows that drinking Matcha tea can reduce anxiety
  12. Older adults: Daunted by a new task? Learn 3 instead
  13. Antioxidant precursor molecule could improve Parkinson’s

 

 

265CNO15JUL2019

NEWS RELEASE 24-JUN-2019

‘Good’ bacteria may prevent — and reverse — food allergy

Study finds key microbes missing from guts of infants with food allergy; restoring these bacteria prevents food allergy and suppresses established disease in mice

BOSTON CHILDREN’S HOSPITAL

BOSTON – June 24, 2019 — A study by scientists at Boston Children’s Hospital and Brigham and Women’s Hospital, published today in Nature Medicine, makes a strong case that the national epidemic of food allergy is caused by the absence of certain beneficial bacteria in the human gut. “The loss of these bacteria acts as a switch that makes children susceptible to food allergy,” says Talal Chatila, MD, director of the Food Allergy Program at Boston Children’s and a senior author on the paper.

But the study, conducted primarily in mice, also points the way toward treatments that may protect children from developing food allergies — and reverse the disease in people who already have it. “We’re hoping this will lead to a treatment for food allergy, not just a preventative approach,” says co-senior author Rima Rachid, MD, assistant director of the Food Allergy Program in Boston Children’s Division of Immunology.

The study, which also tested human gut bacteria, was carried out by Azza Abdel-Gadir, PhD, a former postdoc, and Emmanuel Stephen-Victor, PhD, a current postdoc in Chatila’s lab, both first co-authors on the paper, in collaboration with first co-author Georg Gerber, MD, PhD, and senior co-author Lynn Bry, MD, PhD, both of Brigham and Women’s Hospital.

For reasons that remain a mystery, the number of Americans who suffer from food allergy has risen sharply over the last decade to as many 32 million, according to one recent estimate. Nearly 8 percent of children in the U.S. — about two in every classroom — are affected.

One hypothesis is that certain Western lifestyle factors — an increase in births by Caesarean section, a decline in breastfeeding, increased use of antibiotics and smaller family sizes, for example — is disrupting the normal microbial balance in the gut, depriving babies of the “good” bacteria that prepare the immune system to recognize food as harmless.

Rachid began testing this hypothesis by studying gut bacteria in babies with and without food allergies. Her team collected stool samples from 56 food-allergic patients and 98 matched controls. Gerber and his colleagues at Brigham and Women’s Hospital analyzed those samples for changes in bacterial content. The work revealed that the bacteria in the feces of babies with food allergies were different from those of controls. But did those bacterial differences play a role in their food allergies?

To find out, the team transplanted fecal bacteria from the babies into a special strain of allergy-prone mice. They fed the mice small doses of chicken egg protein to sensitize their immune systems to this allergen, then challenged the mice with a large dose.

The results: Mice that had been given fecal bacteria from food-allergic babies went into the life-threatening reaction called anaphylaxis. “The fecal bacteria from food-allergic subjects did not protect against food allergy, whereas the bacteria from control subjects did,” Chatila says.

To find out which bacteria might be offering that protection, the team turned to Bry at Brigham and Women’s. Bry provided a mix of six bacterial species from the order Clostridiales, which previous studies had suggested might protect against food allergy. When these bacteria were given to the mice, the animals were protected from food allergy to chicken egg protein, whereas mice given other common bacteria were not. “If you give them the right bacteria, the Clostridia, they’re completely resistant to food allergy,” Chatila says.

Bry then provided a second mix of unrelated bacteria from the order Bacteroidales. It too was protective. And finally, when the team treated mice that already had food allergy with the Clostridiales or Bacteroidales mixes, they found those therapies completely suppressed the animals’ allergic reactions.

Chatila believes the study proves that the loss of protective gut bacteria is a critical factor in food allergy. “At the very least it is a fundamental mechanism. And more likely, in my mind, it is the fundamental mechanism on which other things can be layered,” he says.

While previous studies have suggested that certain bacteria can protect against food allergies, Chatila and his colleagues go a step further, describing the specific immunological pathway by which the bacteria act in mice. It begins with a protein, known as MyD88, that serves as a “microbial sensor” in the immune system’s regulatory T cells.

“You need the bacteria to give particular signals that are picked up by nascent regulatory T cells in the gut,” Chatila explains. Those signals trigger a chain reaction that changes the gut regulatory T cells into a specific type, known as ROR-gamma regulatory T cells, that protect against food allergies. As a result of this work, Chatila says, “we now have a fundamental concept of how food allergy happens” — a theory he hopes other scientists will now test.

Chatila and Rachid believe their findings will eventually lead to new treatments that prevent the development of food allergies in newborns at risk. The treatments might take the form of probiotics — mixes of beneficial bacteria — or drugs that prime the immune system in the same way.

And for the millions who already suffer from food allergies, the same treatments may be able to reverse their disease. “Remember,” Chatila says, “in adult mice that had become food-allergic, we could suppress their disease by introducing the good bacteria, which means to us there is the potential to treat somebody with established food allergy and reset their immune system in favor of tolerance.”

Ultimately, Chatila cautions, the promising results in mice will have to be duplicated in humans. But that may happen soon. Rachid is already conducting a first-of-its-kind clinical trial at Boston Children’s to test the safety and efficacy of fecal transplants in adults with peanut allergy. And Chatila notes that several companies are already preparing bacterial mixes for clinical trials. “If the race continues with the same intensity, or accelerates, I think you’ll see a product on the market within five years,” he predicts.

NEWS RELEASE 24-JUN-2019

Discovery of performance-enhancing bacteria in the human microbiome

A single microbe accumulating in the microbiome of elite athletes can enhance exercise performance in mice, paving the way to highly-validated performance-enhancing probiotics

CREDIT: WYSS INSTITUTE AT HARVARD UNIVERSITY

(BOSTON) – The human microbiome, the vast collection of microbes that colonize the surfaces lining many of our organs and our skin – is a critical pillar sustaining our general health. At any one time, 500 to 1,000 different species of bacteria inhabit us, which together contain far more genes than our human genome. Researchers have also come to realize that no two individuals share the same microbiome, and that an individual’s microbiome composition can change with diet, lifestyle, treatment with antibiotics and other drugs, and other factors. Whereas various links have been found between individual microbiomes and diseases as diverse as obesity, inflammatory bowel disease, arthritis, cancer, and autism, it remained unknown whether the opposite also could be true with the microbiome actively enhancing health and physical performance.

“At the start of this project, we hypothesized that the microbiomes of elite athletes must have highly adjusted bacterial species in common that could help with their performance and recovery, and that, once identified, these could become the basis of highly validated performance-enhancing probiotics,” said co-first author Jonathan Scheiman, Ph.D., a former Postdoctoral Fellow who initiated the project with George Church, Ph.D. Core Faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering and Professor at Harvard Medical School (HMS). Scheiman also is the CEO of FitBiomics Inc., and himself a former professional basketball player.

Now, a highly collaborative team of researchers led by Scheiman and Church at the Wyss Institute and HMS, and Aleksandar Kostic at Joslin Diabetes Center in Boston pinpointed one specific group of bacteria, called Veillonella, that they found was enriched in the gut microbiome of Boston Marathon runners after after completing the 26.2 race and in an independent group of 87 elite and Olympic athletes after competitions. Veillonella bacteria isolated from marathon athletes and given to mice increased the animals’ performances in laboratory treadmill tests by 13% compared to control bacteria.

“We were able to demonstrate that the Veillonella-driven performance boost was due to the bacteria’s ability to break down lactate, a metabolite known to accumulate with prolonged strenuous exercise, and to produce propionate, a short-chain fatty acid (SCFA), that in turn enhances the body’s resilience to exercise stress,” said co-corresponding author Kostic, Ph.D., who is Assistant Professor of Microbiology at Joslin Diabetes Center, and pursuing computational and experimental approaches geared at better understanding the relationship between the human microbiome and metabolic diseases such as diabetes.

In their initial analysis of 2015 Boston Marathon runners, the researchers analyzed the runners’ microbiome composition by determining the DNA sequences of an omnipresent but highly species-specific cluster of genes from bacteria obtained from athletes’ stool samples. “Collecting samples daily throughout the week before the run and the week following the run and analyzing them with the help of Aleksandar’s bioinformatics pipeline, enabled us to identify meaningful fluctuations within the entire microbiome with the increase in the Veillonella genus as the most prominent one,” said Scheiman.

Veillonella‘s ability to consume lactate as an energy source was known but the team went a crucial step further. They demonstrated that one single species of Veillonella, known as Veillonella atypica, which they isolated from athletes’ microbiomes and added to the intestinal microbiomes of mice, by itself could boost the animals’ performance in the treadmill running tests.

Key bioinformatics analysis and animal experiments were carried out by co-first authors Jacob Luber, and Theodore Chavkin who both are graduate students in Kostic’s group.

But how? With lactate being produced in working muscles, circulating through the vascular system, and being cleared by the liver, and the bacteria on the other hand residing in the intestinal lumen, there was no obvious connection. Indeed, the team provided the first evidence that lactate can actually cross from the circulation through the intestinal epithelial wall into the gut lumen, where it becomes available to Veillonella and possibly other bacteria. Interestingly, the bacteria did not act as a “lactate sink” causing a sizable drop in systemic circulating lactate levels. Rather, it was a product of the bacteria’s lactate fermentation, the short-chain fatty acid propionate, that crossed back from the gut lumen into the circulation to enhance performance.

The collaborators indeed showed that propionate, when instilled into the intestinal lumen of mice, can reproduce many of Veillonella‘s effects, like the increase in treadmill run time to exhaustion, and a decrease in the levels of common inflammatory markers in the intestinal tract that rise during and after extreme athletic performances and treadmill running in the mouse model. “We think that propionate could exhibit its performance benefits by counter-acting inflammation, serving as an energy source for the body, and other as yet unknown effects,” speculated Kostic. “Of note, higher exercise capacity strongly correlates with milder progression and greater longevity in diabetes patients, which could potentially make a probiotic Veillonella approach therapeutic.”

“The study nicely validated our original hypothesis and provides one of the most compelling examples of ‘metabolic symbiosis’ between the human host and microbiome that could be broadly harnessed as a probiotic strategy not only for athletes but also to improve health in patients,” said co-corresponding author Church, who also is Professor of Genetics at HMS and of Health Sciences and Technology at Harvard University and the Massachusetts Institute of Technology (MIT) and the lead of the Wyss Institute’s Synthetic Biology Platform. “Now that we have built out a platform for identifying microbes associated with extreme performances, we can explore the microbiomes of other types of extreme athletes or individuals that are highly adapted to environmental challenges, uncover additional beneficial functional links and work towards translating them into probiotic treatments.”

Scheiman and Church are co-founders of FitBiomics, Inc., a microbiome biotechnology company targeted at athletes. Scheiman, Church and Kostic hold equity in Fitbiomics, Inc.

“This is a wonderful example of how our Institute provides creative young scientists with the freedom to follow their unconventional ideas wherever they might go. Scheiman’s passion for sports and science merged in a such a wonderful way, and by collaborating with other outstanding scientists, each bringing his own expertise, a major discovery resulted that has the potential to change the quality of life of many people around the world using a low-cost probiotic approach,” said Wyss Institute Founding Director Donald Ingber who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

NEWS RELEASE 24-JUN-2019

Could coffee be the secret to fighting obesity?

UNIVERSITY OF NOTTINGHAM

Scientists from the University of Nottingham have discovered that drinking a cup of coffee can stimulate ‘brown fat’, the body’s own fat-fighting defenses, which could be the key to tackling obesity and diabetes.

The pioneering study, published today in the journal Scientific Reports, is one of the first to be carried out in humans to find components which could have a direct effect on ‘brown fat’ functions, an important part of the human body which plays a key role in how quickly we can burn calories as energy.

Brown adipose tissue (BAT), also known as brown fat, is one of two types of fat found in humans and other mammals. Initially only attributed to babies and hibernating mammals, it was discovered in recent years that adults can have brown fat too. Its main function is to generate body heat by burning calories (opposed to white fat, which is a result of storing excess calories).

People with a lower body mass index (BMI) therefore have a higher amount of brown fat.

Professor Michael Symonds, from the School of Medicine at the University of Nottingham who co-directed the study said: “Brown fat works in a different way to other fat in your body and produces heat by burning sugar and fat, often in response to cold. Increasing its activity improves blood sugar control as well as improving blood lipid levels and the extra calories burnt help with weight loss. However, until now, no one has found an acceptable way to stimulate its activity in humans.

“This is the first study in humans to show that something like a cup of coffee can have a direct effect on our brown fat functions. The potential implications of our results are pretty big, as obesity is a major health concern for society and we also have a growing diabetes epidemic and brown fat could potentially be part of the solution in tackling them.”

The team started with a series of stem cell studies to see if caffeine would stimulate brown fat. Once they had found the right dose, they then moved on to humans to see if the results were similar.

The team used a thermal imaging technique, which they’d previously pioneered, to trace the body’s brown fat reserves. The non-invasive technique helps the team to locate brown fat and assess its capacity to produce heat.

“From our previous work, we knew that brown fat is mainly located in the neck region, so we were able to image someone straight after they had a drink to see if the brown fat got hotter,” said Professor Symonds.

“The results were positive and we now need to ascertain that caffeine as one of the ingredients in the coffee is acting as the stimulus or if there’s another component helping with the activation of brown fat. We are currently looking at caffeine supplements to test whether the effect is similar.

Once we have confirmed which component is responsible for this, it could potentially be used as part of a weight management regime or as part of glucose regulation programme to help prevent diabetes.”

NEWS RELEASE 24-JUN-2019

Study finds micronutrient deficiencies common at time of celiac disease diagnosis

MAYO CLINIC

ROCHESTER, Minn. — Micronutrient deficiencies, including vitamins B12 and D, as well as folate, iron, zinc and copper, are common in adults at the time of diagnosis with celiac disease. These deficiencies should be addressed at that time, according to a study by Mayo Clinic researchers.

The retrospective study of 309 adults newly diagnosed with celiac disease at Mayo Clinic from 2000 to 2014 also found that low body weight and weight loss, which are commonly associated with celiac disease, were less common. Weight loss was seen in only 25.2% of patients, and the average body mass index was categorized as overweight. The study will appear in the July issue of Mayo Clinic Proceedings.

“It was somewhat surprising to see the frequency of micronutrient deficiencies in this group of newly diagnosed patients, given that they were presenting fewer symptoms of malabsorption,” says Adam Bledsoe, M.D., a gastroenterology fellow at Mayo Clinic’s Rochester campus.

Celiac disease is an immune reaction to consuming gluten, a protein found in wheat, barley and rye. Eating gluten triggers an immune response in the small intestine that over time damages the intestine’s lining and prevents it from absorbing some nutrients, leading to diarrhea, fatigue, anemia, weight loss and other complications.

Based on recent data, the prevalence of celiac disease in the U.S. is 1 in 141 people, and its prevalence has increased over the past 50 years.

“Our study suggests that the presentation of celiac disease has changed from the classic weight loss, anemia and diarrhea, with increasing numbers of patients diagnosed with nonclassical symptoms,” says Dr. Bledsoe, the study’s primary author. “Micronutrient deficiencies remain common in adults, however, and should be assessed.” Assessment should include vitamin D, iron, folic acid, vitamin B12, zinc and copper.

Zinc deficiency was observed most frequently at diagnosis, the study says, with 59.4% of patients having a deficiency. Other deficiencies included iron, vitamin D, copper, vitamin B12 and folate.

The nutritional deficiencies have potential health ramifications, though in this retrospective study the clinical implications remain unknown. “Further studies are needed to better define the implications of the deficiencies, optimal replacement strategies and follow-up,” says Dr. Bledsoe.

NEWS RELEASE 23-JUN-2019

Cannabidiol is a powerful new antibiotic

AMERICAN SOCIETY FOR MICROBIOLOGY

San Francisco, CA – June 23, 2019 – New research has found that Cannnabidiol is active against Gram-positive bacteria, including those responsible for many serious infections (such as Staphyloccocus aureus and Streptococcus pneumoniae), with potency similar to that of established antibiotics such as vancomycin or daptomycin. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology.

Cannabidiol, the main non-psychoactive chemical compound extracted from cannabis and hemp plants, has been approved by FDA for the treatment of a form of epilepsy, and is being investigated for a number of other medical conditions, including, anxiety, pain and inflammation. While there is limited data to suggest Cannabidiol can kill bacteria, the drug has not been thoroughly investigated for its potential as an antibiotic.

Work led by Dr Mark Blaskovich at The University of Queensland’s Institute for Molecular Bioscience’s Centre for Superbug Solutions, in collaboration with Botanix Pharmaceuticals Ltd, an early stage drug discovery company investigating topical uses of synthetic cannabidiol for a range of skin conditions, found that Cannabidiol was remarkably effective at killing a wide range of Gram-positive bacteria, including bacteria that have become resistant to other antibiotics, and did not lose effectiveness after extended treatment.

“Given cannabidiol’s documented anti-inflammatory effects, existing safety data in humans, and potential for varied delivery routes, it is a promising new antibiotic worth further investigation,” said Dr. Blaskovich. “The combination of inherent antimicrobial activity and potential to reduce damage caused by the inflammatory response to infections is particularly attractive.”

Importantly, the drug retained its activity against bacteria that have become highly resistant to other common antibiotics. Under extended exposure conditions that lead to resistance against vancomycin or daptomycin, Cannabidiol did not lose effectiveness. Cannabidiol was also effective at disrupting biofilms, a physical form of bacteria growth that leads to difficult-to-treat infections.

The project was co-funded by Botanix and Innovation Connections, an Australian government grant scheme to commercialize new products, processes and services. The paper will be presented on Sunday June 23rd from 11am-1 pm at the annual conference of the American Society for Microbiology, ASM Microbe 2019, at the Moscone Convention Center in San Francisco.

NEWS RELEASE 21-JUN-2019

Plant-based diet leads to Crohn’s Disease remission, according to case study

PHYSICIANS COMMITTEE FOR RESPONSIBLE MEDICINE

Eating a plant-based diet may be an effective treatment for Crohn’s disease, according to a case study published in the journal Nutrients.

The case study followed a man in his late 20s who had been diagnosed with Crohn’s disease after experiencing fatigue, bloating, episodic severe abdominal pain, nausea, and occasional ulcers for several years. His condition did not reach remission after more than a year of intravenous treatment.

During his second year of treatment, the patient removed all animal products and processed foods from his diet for a 40-day religious observation and experienced a total absence of symptoms. The patient decided to maintain the new dietary pattern–which was based on fruits, vegetables, whole grains, and legumes–and experienced a complete remission of Crohn’s disease. Tests showed complete mucosal healing, and the patient was able to cease medications. He reports no relapses since.

“This case study offers hope for hundreds of thousands of people suffering from the painful symptoms associated with Crohn’s disease,” says study co-author Hana Kahleova, MD, PhD, director of clinical research at the Physicians Committee for Responsible Medicine.

Using current treatment regimens, only about 10 percent of traditionally managed Crohn’s disease patients achieve long-term remission, and 50 percent of patients require surgery within 10 years of diagnosis.

The study authors note that plant-based diets are high in fiber, which promotes overall gut health. Fiber also feeds the healthy bacteria in the gut–which may offer a protective effect against Crohn’s disease and other digestive problems. While more research is needed, previous studies have supported the conclusion that diets rich in plant proteins and whole foods may benefit Crohn’s disease patients.

“This case study supports the idea that food really is medicine,” adds Dr. Kahleova. “Not only does it show that eating a high-fiber, plant-based diet could help lead to Crohn’s disease remission, but all the ‘side effects’ are good ones, including a reduced risk for heart disease, type 2 diabetes, and certain types of cancer.”

NEWS RELEASE 20-JUN-2019

Study: Phenols in cocoa bean shells may reverse obesity-related problems in mouse cells

UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN, NEWS BUREAU

CHAMPAIGN, Ill. — Scientists may have discovered more reasons to love chocolate.

A new study by researchers at the University of Illinois suggests that three of the phenolic compounds in cocoa bean shells have powerful effects on the fat and immune cells in mice, potentially reversing the chronic inflammation and insulin resistance associated with obesity.

Visiting scholar in food science Miguel Rebollo-Hernanz and Elvira Gonzalez de Mejia, a professor in the department, found that cocoa shells contain high levels of three beneficial bioactive chemicals also found in cocoa, coffee and green tea – protocatechuic acid, epicatechin and procyanidin B2.

Rebollo-Hernanz, the study’s lead author, created a water-based extract containing these compounds and tested its effects on white fat cells called adipocytes and immune cells called macrophages. Using computer modeling and bioinformatic techniques, he also examined the impact that each of the phenolics individually had on the cells.

“The objectives of the study were to test whether the bioactive compounds in the cocoa shells were efficacious against macrophages – the inflammatory cells – at eliminating or reducing the biomarkers of inflammation,” said de Mejia, also a director of nutritional sciences. “We wanted to see if the phenolics in the extract blocked or reduced the damage to fat cells’ mitochondria and prevented insulin resistance.”

Similar to batteries within cells that burn fat and glucose to generate energy, mitochondria can become damaged when high levels of fat, glucose and inflammation occur in the body, de Mejia said.

When the scientists treated adipocytes with the aqueous extract or the three phenolic compounds individually, damaged mitochondria in the cells were repaired and less fat accumulated in the adipocytes, blocking inflammation and restoring the cells’ insulin sensitivity, Rebollo-Hernanz said.

The scientists reported their findings recently in a paper published in the journal Molecular Nutrition and Food Research.

When adipocytes accumulate too much fat, they promote the growth of macrophages. This initiates a toxic cycle in which the adipocytes and macrophages interact, emitting toxins that inflame fat tissue, de Mejia said.

Over time, this chronic inflammation impairs cells’ ability to take up glucose, leading to insulin resistance and possibly type 2 diabetes as glucose levels in the blood escalate.

To recreate the inflammatory process that occurs in the body when macrophages and adipocytes begin their toxic dance, Rebollo-Hernanz grew adipocytes in a solution in which macrophages had been cultured.

“That’s when we observed that these inflammatory conditions in the solution increased the oxidative damage” to the fat cells’ mitochondria, he said.

Fewer mitochondria were present in the adipocytes that were grown in the solution, and the mitochondria that did exist in these cells were damaged, he found.

When the scientists treated the adipocytes with the phenolics in the extract, however, the adipocytes underwent a process called browning, in which they differentiated – that is, converted – from white adipocytes into another form called beige adipocytes.

Beige adipocytes are a specialized form of fat tissue with greater numbers of mitochondria and enhanced fat-burning efficiency.

“We observed that the extract was able to maintain the mitochondria and their function, modulating the inflammatory process and maintaining the adipocytes’ sensitivity to insulin,” Rebollo-Hernanz said. “Assuming that these phenolics were the main actors in this extract, we can say that consuming them could prevent mitochondrial dysfunction in adipose tissue.”

Cocoa shells are a waste byproduct that’s generated when cocoa beans are roasted during chocolate production. About 700,000 tons of the shells are discarded annually, causing environmental contamination if not disposed of responsibly, de Mejia said.

In addition to providing cocoa producers with another potential revenue stream, processing the shells to extract the nutrients would reduce the environmental toxicants generated currently by cocoa shell waste, de Mejia said.

Once extracted from cocoa bean shells, the phenolic compounds could be added to foods or beverages to boost products’ nutritional value, she said.

NEWS RELEASE 20-JUN-2019

Processed foods may hold key to rise in autism

UNIVERSITY OF CENTRAL FLORIDA

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With the number of children diagnosed with autism on the rise, the need to find what causes the disorder becomes more urgent every day. UCF researchers are now a step closer to showing the link between the food pregnant women consume and the effects on a fetus’ developing brain.

Drs. Saleh Naser, Latifa Abdelli and UCF undergraduate research assistant Aseela Samsam have identified the molecular changes that happen when neuro stem cells are exposed to high levels of an acid commonly found in processed foods. In a study published June 19 in Scientific Reports, a Nature journal, the UCF scientists discovered how high levels of Propionic Acid (PPA), used to increase the shelf life of packaged foods and inhibit mold in commercially processed cheese and bread, reduce the development of neurons in fetal brains.

Dr. Naser, who specializes in gastroenterology research at the College of Medicine’s Burnett School of Biomedical Sciences, began the study after reports showed that autistic children often suffer from gastric issues such as irritable bowel syndrome. He wondered about a possible link between the gut and the brain and began examining how the microbiome — or gut bacteria — differed between people with autism and those who do not have the condition.

“Studies have shown a higher level of PPA in stool samples from children with autism and the gut microbiome in autistic children is different,” Dr. Naser said. “I wanted to know what the underlying cause was.”

In the lab, the scientists found exposing neural stem cells to excessive PPA damages brain cells in several ways. First, the acid disrupts the natural balance between brain cells by reducing the number of neurons and over-producing glial cells. While glial cells help develop and protect neuron function, too many glia cells disturb connectivity between neurons. They also cause inflammation, which has been noted in the brains of autistic children.

Excessive amounts of the acid also shorten and damage pathways that neurons use to communicate with the rest of the body. The combination of reduced neurons and damaged pathways impede the brain’s ability to communicate, resulting in behaviors that are often found in children with autism, including repetitive behavior, mobility issues and inability to interact with others.

Previous studies have proposed links between autism and environmental and genetic factors, but Drs. Naser and Abdelli say their study is the first to discover the molecular link between elevated levels of PPA, proliferation of glial cells, disturbed neural circuitry and autism. The 18-month study was self-funded by UCF.

PPA occurs naturally in the gut and a mother’s microbiome changes during pregnancy and can cause increases in the acid. But Drs. Naser and Abdelli said eating packaged foods containing the acid can further increase PPA in the woman’s gut, which then crosses to the fetus.

More research needs to be done before drawing clinical conclusions. Next, the research team will attempt to validate its findings in mice models by seeing if a high PPA maternal diet causes autism in mice genetically predisposed to the condition. There is no cure for autism, which affects about 1 in 59 children, but the scientists hope their findings will advance studies for ways to prevent the disorder.

“This research is only the first step towards better understanding of Autism Spectrum Disorder,” the UCF scientists concluded. “But we have confidence we are on the right track to finally uncovering autism etiology.”

NEWS RELEASE 27-JUN-2019

Goat milk formula could benefit infant gut health: Study

RMIT UNIVERSITY

The laboratory study by RMIT, published in the British Journal of Nutrition, analysed two types of commercial goat milk formula.

The research looked at oligosaccharides, a type of prebiotic that can boost the growth of beneficial bacteria and protect against harmful bacteria in the gut.

Researchers found 14 naturally-occurring prebiotic oligosaccharides in the goat milk formula. Five of these are also found in human breast milk.

Lead investigator, Professor Harsharn Gill, said the study was believed to be the first to reveal the diversity of oligosaccharides in goat’s milk-based infant formula and their similarity to human milk.

“Our results show goat milk formula may have strong prebiotic and anti-infection properties, that could protect infants against gastrointestinal infections,” Gill said.

“The study indicates the prebiotic oligosaccharides in goat milk formula are effective at selectively promoting the growth of healthy bacteria in the gut.

“While these laboratory results are promising, further research including clinical trials will help us to confirm these benefits for infants.”

Human milk contains an abundant supply and diverse array of oligosaccharides that are known to offer significant health benefits to babies, including the establishment and maintenance of a healthy gut microflora, immune development and protection against gastrointestinal infections.

When breastfeeding is not possible or insufficient, infant formulas are commonly used as an alternative but there is limited information available about the oligosaccharides they may contain or their likely health benefits.

The new study examined the presence of naturally occurring oligosaccharides in two goat milk formulas (Oli6 Stage 1 for babies aged 0-6 months and Oli6 Stage 2 for babies aged 6-12 months) and their prebiotic and anti-infection properties.

While cow milk formula is the most widely used alternative to breastfeeding, goat milk is considered to be closer to human milk in some respects, especially oligosaccharides.

The study found the natural prebiotic oligosaccharides in the goat milk formula were effective in promoting the growth of beneficial bacteria (bifidobacteria) and inhibiting the ability of harmful bacteria such as pathogenic E. coli to attach to human intestinal cells.

Almost one third of all cases of diarrhoea in children are attributed to pathogenic E. colibacteria.

The researchers found two types of oligosaccharides – fucosylated and sialylated – were most heavily present in the goat milk formula.

“Fucosylated are the most abundant oligosaccharides in human milk and are the focus of significant commercial and regulatory interest,” Gill said.

“These oligosaccharides have been shown to play a significant role in anti-infection properties of breast milk.”

Researchers in RMIT’s School of Science are now planning to undertake clinical trials to confirm the results of the study.

The research was supported by RMIT and an Entrepreneurs’ Programme: Innovation Connections Grant co-funded by the Australian Government and Nuchev Pty Ltd, manufacturers of Oli6.

Nuchev had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; and in the decision to publish the results.

The research is published in the British Journal of Nutrition (“Oligosaccharides in goats’ milk-based infant formula and their prebiotic and anti-infection properties“, DOI: 10.1017/S000711451900134X) and was presented at the 2019 Annual Nutrition Conference of the American Society of Nutrition in Baltimore, USA.

NEWS RELEASE 27-JUN-2019

Low-carb ‘keto’ diet (‘Atkins-style’) may modestly improve cognition in older adults

Diet that restricts glucose may help brain function

JOHNS HOPKINS MEDICINE

In a pilot study of 14 older adults with mild cognitive problems suggestive of early Alzheimer’s disease, Johns Hopkins Medicine researchers report that a high-fat, low-carbohydrate diet may improve brain function and memory.

Although the researchers say that finding participants willing to undertake restrictive diets for the three-month study — or partners willing to help them stick to those diets — was challenging, those who adhered to a modified Atkins diet (very low carbohydrates and extra fat) had small but measurable improvements on standardized tests of memory compared with those on a low-fat diet.

The short-term results, published in the April issue of the Journal of Alzheimer’s Disease, are far from proof that the modified Atkins diet has the potential to stave off progression from mild cognitive impairment to Alzheimer’s disease or other dementias. However, they are promising enough, the researchers say, to warrant larger, longer-term studies of dietary impact on brain function.

“Our early findings suggest that perhaps we don’t need to cut carbs as strictly as we initially tried. We may eventually see the same beneficial effects by adding a ketone supplement that would make the diet easier to follow,” says Jason Brandt, Ph.D., professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine. “Most of all, if we can confirm these preliminary findings, using dietary changes to mitigate cognitive loss in early-stage dementia would be a real game-changer. It’s something that 400-plus experimental drugs haven’t been able to do in clinical trials.”

Brandt explains that, typically, the brain uses the sugar glucose — a product of carbohydrate breakdown — as a primary fuel. However, research has shown that in the early stage of Alzheimer’s disease the brain isn’t able to efficiently use glucose as an energy source. Some experts, he says, even refer to Alzheimer’s as “type 3 diabetes.”

Using brain scans that show energy use, researchers have also found that ketones — chemicals formed during the breakdown of dietary fat — can be used as an alternative energy source in the brains of healthy people and those with mild cognitive impairment. For example, when a person is on a ketogenic diet, consisting of lots of fat and very few sugars and starches, the brain and body use ketones as an energy source instead of carbs.

For the current study, the researchers wanted to see if people with mild cognitive impairment, often an indicator of developing Alzheimer’s disease, would benefit from a diet that forced the brain to use ketones instead of carbohydrates for fuel.

After 2 1/2 years of recruitment efforts, the researchers were able to enroll 27 people in the 12-week diet study. There were a few dropouts, and so far, 14 participants have completed the study. The participants were an average age of 71. Half were women, and all but one were white.

To enroll, each participant required a study partner (typically a spouse) who was responsible for ensuring that the participant followed one of two diets for the full 12 weeks. Nine participants followed a modified Atkins diet meant to restrict carbs to 20 grams per day or less, with no restriction on calories. The typical American consumes between 200 and 300 grams of carbs a day. The other five participants followed a National Institute of Aging diet, similar to the Mediterranean diet, that doesn’t restrict carbohydrates, but favors fruits, vegetables, low- or fat-free dairy, whole grains and lean proteins such as seafood or chicken.

The participants and their partners were also asked to keep food diaries. Prior to starting the diets, those assigned to the modified Atkins diet were consuming about 158 grams of carbs per day. By week six of the diet, they had cut back to an average of 38.5 grams of carbs per day and continued dropping at nine weeks, but still short of the 20-gram target, before rising to an average of 53 grams of carbs by week 12. Participants on the National Institute of Aging diet continued to eat well over 100 grams of carbs per day.

Each participant also gave urine samples at the start of the dietary regimens and every three weeks up to the end of the study, which were used to track ketone levels. More than half of the participants on the modified Atkins diet had at least some ketones in their urine by six weeks into the diet until the end; as expected, none of the participants on the National Institute of Aging control diet had any detectable ketones.

Participants completed the Montreal Cognitive Assessment, the Mini-Mental State Examination and the Clinical Dementia Rating Scale at the start of the study. They were tested with a brief collection of neuropsychological memory tests before starting their diets and at six weeks and 12 weeks on the diet. At the six-week mark, the researchers found a significant improvement on memory tests, which coincided with the highest levels of ketones and lowest carb intakes.

When comparing the results of tests of delayed recall — the ability to recollect something they were told or shown a few minutes earlier — those who stuck to the modified Atkins diet improved by a couple of points on average (about 15% of the total score), whereas those who didn’t follow the diet on average dropped a couple of points.

The researchers say the biggest hurdle for researchers was finding people willing to make drastic changes to their eating habits and partners willing to enforce the diets. The increase in carbohydrate intake later in the study period, they said, suggests that the diet becomes unpalatable over long periods.

“Many people would rather take a pill that causes them all kinds of nasty side effects than change their diet,” says Brandt. “Older people often say that eating the foods they love is one of the few pleasures they still enjoy in life, and they aren’t willing to give that up.”

But, because Brandt’s team observed promising results even in those lax with the diet, they believe that a milder version of the high-fat/low-carb diet, perhaps in conjunction with ketone supplement drinks, is worth further study. As this study also depended on caregivers/partners to do most of the work preparing and implementing the diet, the group also wants to see if participants with less severe mild cognitive impairment can make their own dietary choices and be more apt to stick to a ketogenic diet.

A standardized modified Atkins diet was created and tested at Johns Hopkins Medicine in 2002, initially to treat some seizure disorders. It’s still used very successfully for this purpose.

According to the Alzheimer’s Association, about 5.8 million Americans have Alzheimer’s disease, and by 2050 the number is projected to increase to 14 million people.

This research was supported by the William and Ella Owens Medical Research Foundation, the BrightFocus Foundation and the National Center for Advancing Translational Sciences (UL1-TR001079). The Hass Avocado Board donated avocados to participants.

Cervenka has consulted for Nutricia and Sage Therapeutics. She has received grants from Nutricia and Vitaflo. Henry-Barron has consulted for Nutricia and Vitaflo and lectured for Nutricia.

NEWS RELEASE 8-JUL-2019

Research shows that drinking Matcha tea can reduce anxiety

KUMAMOTO UNIVERSITY

Many different countries have a tea culture, and Japanese Matcha tea is growing in popularity around the world. In Japan, Matcha has a long history of being used for various medicinal purposes. It has been suspected to have various beneficial effects to health, but relatively little scientific evidence supported that claim. Now, a group of Japanese researchers from Kumamoto University has shown that anxious behavior in mice is reduced after consuming Matcha powder or Matcha extract. Its calming effects appear to be due to mechanisms that activate dopamine D1 receptors and serotonin 5-HT1A receptors, both of which are closely related to anxious behavior.

Matcha is the finely ground powder of new leaves from shade-grown (90% shade) Camellia sinensis green tea bushes. The tea (and food flavoring) is enjoyed around the world. In Japan, historical medicinal uses for Matcha included helping people relax, preventing obesity, and treatment of skin conditions. The researchers, therefore, sought to determine its various beneficial effects.

The “elevated plus maze” test is an elevated, plus-shaped, narrow platform with two walled arms that provide safety for the test subject, typically a mouse. It is used as an anxiety test for rodents with the idea that animals experiencing higher anxiety will spend more time in the safer walled-off areas. Using this test, researchers found that mouse anxiety was reduced after consuming Matcha powder or Matcha extract. In addition, when the anxiolytic activity of different Matcha extracts were evaluated, a stronger effect was found with the extract derived using 80% ethanol in comparison to the extract derived from only hot water. In other words, a poorly water-soluble Matcha component has stronger anxiolytic effects than a component that is easily soluble in water. A behavioral pharmacological analysis further revealed that Matcha and Matcha extracts reduce anxiety by activating dopamine D1 and serotonin 5-HT1Areceptors.

“Although further epidemiological research is necessary, the results of our study show that Matcha, which has been used as medicinal agent for many years, may be quite beneficial to the human body,” said study leader, Dr. Yuki Kurauchi. “We hope that our research into Matcha can lead to health benefits worldwide.”

NEWS RELEASE 17-JUL-2019

Older adults: Daunted by a new task? Learn 3 instead

Learning multiple things simultaneously increases cognitive abilities in older adults, new UC Riverside research finds

UNIVERSITY OF CALIFORNIA – RIVERSIDE

Learning several new things at once increases cognitive abilities in older adults, according to new research from UC Riverside.

UCR psychologist Rachel Wu says one important way of staving off cognitive decline is learning new skills as a child would. That is, be a sponge: seek new skills to learn; maintain motivation as fuel; rely on encouraging mentors to guide you; thrive in an environment where the bar is set high.

“The natural learning experience from infancy to emerging adulthood mandates learning many real-world skills simultaneously,” Wu’s research team writes in a paper recently published in The Journals of Gerontology, Series B: Psychological Sciences.

Likewise, the group’s hypothesis held, learning multiple new skills in an encouraging environment in older adulthood leads to cognitive growth. The prize: maintaining independence in old age.

Building on lifelong learning research, previous studies have demonstrated the cognitive gains of older people learning new skills, such as photography or acting. But these skills were learned one at a time, or sequentially.

For Wu’s studies, the researchers asked adults 58 to 86 years old to simultaneously take three to five classes for three months — about 15 hours per week, similar to an undergraduate course load. The classes included Spanish, learning to use an iPad, photography, drawing/painting, and music composition.

The participants completed cognitive assessments before, during, and after the studies to gauge working memory (such as remembering a phone number for a few minutes); cognitive control (which is switching between tasks) and episodic memory (such as remembering where you’ve parked).

After just 1 ½ months, participants increased their cognitive abilities to levels similar to those of middle-aged adults, 30 years younger. Control group members, who did not take classes, showed no change in their performance.

“The participants in the intervention bridged a 30 year difference in cognitive abilities after just 6 weeks and maintained these abilities while learning multiple new skills,” said Wu, who is an assistant professor of psychology.

“The take-home message is that older adults can learn multiple new skills at the same time, and doing so may improve their cognitive functioning,” Wu said. “The studies provide evidence that intense learning experiences akin to those faced by younger populations are possible in older populations, and may facilitate gains in cognitive abilities.”

NEWS RELEASE 16-JUL-2019

Antioxidant precursor molecule could improve Parkinson’s

The naturally occurring molecule N-acetylcysteine (NAC) shows benefit in a clinical trial for Parkinson’s Disease

THOMAS JEFFERSON UNIVERSITY

(PHILADELPHIA) – N-acetylcysteine (NAC) is a naturally occurring molecule that replenishes one of the body’s antioxidants and now shows potential benefit as part of a standard course of treatment for patients with Parkinson’s disease, according to a study published in the journal, Clinical Pharmacology & Therapeutics. The study found improvements in dopamine levels, the primary neurotransmitter that is specifically decreased in Parkinson’s disease, as well as improvements in clinical evaluations of the patients’ mental and physical abilities. The study was performed by the Department of Integrative Medicine and Nutritional Sciences, as well as the Departments of Neurology and Radiology, at Thomas Jefferson University.

Current treatments for Parkinson’s disease are generally limited to temporarily replacing dopamine in the brain along with medications designed to slow the progression of the disease. The destruction of dopamine nerve cells in Parkinson’s disease appears to result in large part due to oxidative stress which lowers levels of glutathione, a chemical produced by the brain to counteract oxidative stress. NAC is an oral supplement, and also comes in an intravenous form that is used to protect the liver in acetaminophen overdose. Several initial studies have shown that NAC administration increases glutathione levels in the brain, but it has not been tested whether such an effect would augment dopamine levels as neurons recover function. The current study tested this by tracking dopamine re-uptake via brain scans.

“This study is an important step in understanding how N-acetylcysteine might work as a potentially new avenue for managing Parkinson’s patients. The NAC appears to enable dopamine neurons to recover some of their function,” said senior author on the paper Daniel Monti, MD, Chairman of the Department of Integrative Medicine and Nutritional Sciences and Director of the Marcus Institute of Integrative Health at Thomas Jefferson University.

This study advanced earlier findings that NAC may increase dopamine function in patients with Parkinson’s disease. In the study, 42 patients with Parkinson’s disease continued their current treatment and were placed into two groups – the first group received a combination of oral and intravenous (IV) NAC for three months (in addition to their current treatment program); and the second group, the control patients, received only their standard-of-care Parkinson’s treatment for three months. Those patients in the active group received 50mg/kg NAC intravenously once per week and 500mg NAC orally 2x per day on the non IV days.

Patients were evaluated clinically using the Unified Parkinson’s Disease Rating Scale (UPDRS), which assesses a variety of symptoms including both cognitive and motor function. Patients also underwent brain scanning using DaTscan SPECT imaging which measures the amount of dopamine transporter in the basal ganglia, the area most affected by the Parkinson’s disease process. This test was used to determine the level of neuronal recovery. Patients were evaluated initially and after three months of either receiving the NAC or standard of care therapy.

Compared to controls, the patients receiving NAC had improvements of 4-9% in dopamine transporter binding and also showed improvements in their UPDRS score of about 14%.

“This is an exciting study that suggests a natural molecule such as NAC can help improve dopamine function and symptoms in Parkinson’s patients,” said corresponding author and neuro-imaging expert Andrew Newberg, M.D., Professor and Director of Research at the Department of Integrative Medicine and Nutritional Sciences. The investigators hope that this research will open up new avenues of treatment for Parkinson’s disease patients.

 

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