Common gut bacteria prevent sensitization to allergens in a mouse model for peanut allergy, paving the way for probiotic therapies to treat food allergies

From FMS Global News Desk of Jeanne Hambleton Embargoed: 25-Aug-2014 Citations Proceedings of the National Academy of Sciences
Source Newsroom: University of Chicago Medical Center


Newswise — The presence of Clostridia, a common class of gut bacteria, protects against food allergies, a new study in mice finds. By inducing immune responses that prevent food allergens from entering the bloodstream, Clostridia minimize allergen exposure and prevent sensitization – a key step in the development of food allergies. The discovery points toward probiotic therapies for this so-far untreatable condition, report scientists from the University of Chicago, Aug 25 in the Proceedings of the National Academy of Sciences.

Although the causes of food allergy – a sometimes deadly immune response to certain foods – are unknown, studies have hinted that modern hygienic or dietary practices may play a role by disturbing the body’s natural bacterial composition. In recent years, food allergy rates among children have risen sharply – increasing approximately 50 percent between 1997 and 2011 – and studies have shown a correlation to antibiotic and antimicrobial use.

“Environmental stimuli such as antibiotic overuse, high fat diets, caesarean birth, removal of common pathogens and even formula feeding have affected the microbiota with which we have co-evolved,” said study senior author Cathryn Nagler, PhD, Bunning Food Allergy Professor at the University of Chicago.

“Our results suggest this could contribute to the increasing susceptibility to food allergies.”

To test how gut bacteria affect food allergies, Nagler and her team investigated the response to food allergens in mice. They exposed germ-free mice (born and raised in sterile conditions to have no resident microorganisms) and mice treated with antibiotics as newborns (which significantly reduces gut bacteria) to peanut allergens. Both groups of mice displayed a strong immunological response, producing significantly higher levels of antibodies against peanut allergens than mice with normal gut bacteria.

This sensitization to food allergens could be reversed, however, by reintroducing a mix of Clostridia bacteria back into the mice. Reintroduction of another major group of intestinal bacteria, Bacteroides, failed to alleviate sensitization, indicating that Clostridia have a unique, protective role against food allergens.

Closing the door

To identify this protective mechanism, Nagler and her team studied cellular and molecular immune responses to bacteria in the gut. Genetic analysis revealed that Clostridia caused innate immune cells to produce high levels of interleukin-22 (IL-22), a signaling molecule known to decrease the permeability of the intestinal lining.

Antibiotic-treated mice were either given IL-22 or were colonized with Clostridia. When exposed to peanut allergens, mice in both conditions showed reduced allergen levels in their blood, compared to controls. Allergen levels significantly increased, however, after the mice were given antibodies that neutralized IL-22, indicating that Clostridia-induced IL-22 prevents allergens from entering the bloodstream.

“We have identified a bacterial population that protects against food allergen sensitization,” Nagler said. “The first step in getting sensitized to a food allergen is for it to get into your blood and be presented to your immune system. The presence of these bacteria regulates that process.” She cautions, however, that these findings likely apply at a population level, and that the cause-and-effect relationship in individuals requires further study.

While complex and largely undetermined factors such as genetics greatly affect whether individuals develop food allergies and how they manifest, the identification of a bacteria-induced barrier-protective response represents a new paradigm for preventing sensitization to food. Clostridia bacteria are common in humans and represent a clear target for potential therapeutics that prevent or treat food allergies. Nagler and her team are working to develop and test compositions that could be used for probiotic therapy and have filed a provisional patent.

“It is exciting because we know what the bacteria are; we have a way to intervene,” Nagler said. “There are of course no guarantees, but this is absolutely testable as a therapeutic against a disease for which there’s nothing. As a mom, I can imagine how frightening it must be to worry every time your child takes a bite of food.”

“Food allergies affect 15 million Americans, including one in 13 children, who live with this potentially life-threatening disease that currently has no cure,” said Mary Jane Marchisotto, senior vice president of research at Food Allergy Research & Education. “We have been pleased to support the research that has been conducted by Dr. Nagler and her colleagues at the University of Chicago.”

The study, “Commensal bacteria protect against food allergen sensitization,” was supported by Food Allergy Research & Education (FARE) and the University of Chicago Digestive Diseases Research Core Center. Additional authors include Andrew T. Stefka, Taylor Feehley, Prabhanshu Tripathi, Ju Qiu, Kathy D. McCoy, Sarkis K. Mazmanian, Melissa Y. Tjota, Goo-Young Seo, Severine Cao, Betty R. Theriault, Dionysios A. Antonopoulos, Liang Zhou, Eugene B. Chang and Yang-Xin Fu.

Food Allergy Research & Education (FARE) is a 501(c)(3) nonprofit organization that seeks to find a cure for food allergies while keeping affected individuals safe and included. FARE does this by investing in world-class research that advances the treatment and understanding of the disease, providing evidence-based education and resources, undertaking advocacy at all levels of government and increasing awareness of food allergy as a serious public health issue.

The University of Chicago Medicine
The University of Chicago Medicine and Biological Sciences is one of the nation’s leading academic medical institutions. It comprises the Pritzker School of Medicine, a top medical school in the nation; the University of Chicago Biological Sciences Division; and the University of Chicago Medical Center, which recently opened the Center for Care and Discovery, a $700 million specialty medical facility. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine.



Study aims to uncover processes that help improve theoretical knowledge

From the FMS Global News Desk of Jeanne Hambleton
National Science Foundation  August 2014  Harvard University

What is it about the human mind, as opposed to those of other animals, that makes it able to comprehend and reason about complex concepts such as infinity, cancer or protons?
That is what National Science Foundation (NSF)-funded research conducted by Harvard University professors Susan Carey and Deborah Zaitchik seeks to find out.

The two investigators are leading a new project that explores how children develop understanding of abstract concepts over time, specifically in mathematics and in science–biology, psychology and physics. Their research could prove transformative to the practice of education.

Carey and Zaitchik’s project, “Executive Function and Conceptual Change,” is one of 40 projects funded in the first round of an NSF initiative called INSPIRE that address extremely complicated and pressing scientific problems.

Specifically, the project aims to determine how children develop theoretical concepts of science and math and how the learning process might be modified to increase their level of understanding.

NSF’s Developmental and Learning Sciences Program in its Directorate for Social, Behavioral and Economic Sciences partially funds the research. It is one item in a program portfolio that strives to understand how children learn, and what factors influence their social and thinking skills as they become productive members of society.

Past research shows children have intuitive theories about science and math before they begin formal learning. Their intuitive theories are often radically different from the theories taught in school, but through schoolwork, are transformed into standard, often abstract ideas that were previously unknown to the students.

For example, children believe the earth is flat and draw conclusions about the world based on that assumption. When they become aware the world is round, they must update their knowledge about the shape of the earth and also update the kinds of conclusions they can draw about the world in light of this new information, such as that it is impossible to fall off its edge.

This transformation involves what Carey and Zaitchik call conceptual change–a process by which a person’s knowledge and beliefs are modified over time and evolve into a new conceptual system of interconnected knowledge and reasoning.

Conceptual change is extremely difficult to achieve. Studies show it requires more than gathering new facts to replace or modify old facts; it demands, in addition, sustained mental effort to integrate all related pieces of information into a coherent body of knowledge.

“The kind of knowledge we are talking about is hard to construct,” says Carey, a Harvard psychologist and the project’s lead principal investigator. “You just do not get it for free.”
The difficulty of conceptual change is one of the reasons teaching science and math is such a challenge. It is also a reason the Research on Education and Learning (REAL) program within NSF’s Directorate for Education and Human Resources (EHR) co-funds the project.

“This project helps build the bridge between research on the brain and applications to improve math and science education,” said Evan Heit, a program director for EHR’s REAL program.

“By tackling complex, real-world problems related to education, this research can improve scientific understanding of the brain and also suggest ways to help young children who are facing challenges as they learn about math and science.”

Carey and Zaitchik believe that if the cognitive processes needed to produce conceptual change can be identified, better understood and successfully manipulated through simple training, it might make a big difference in a student’s academic success, whether that student is in kindergarten or college.

They are especially concerned with how a suite of cognitive processes called “executive function” impacts children’s ability to both build new abstract knowledge and use it throughout their lifetimes.

The components of executive function under investigation by the research team include working memory, inhibitory control and set-shifting. Working memory involves the ability to actively hold information in mind, update it and mentally work with it. Inhibitory control is the ability to suppress interference, distractions and inappropriate responses, which is important for completing cognitive tasks. Set-shifting involves the ability to flexibly switch goals or modes of operation, such as recognizing that different problem-solving approaches will be more successful in different settings.

Previous research has shown that executive function is more predictive of school readiness than entry-level reading skills, entry-level math skills or IQ. In addition, executive function has been shown to play an important role throughout a person’s school years, with working memory and inhibitory control independently predicting math and reading score success in every grade from preschool through high school.

Carey and Zaitchik say there is already a good deal of empirical evidence that these processes play a strong role in school children’s ability to learn and express theoretical knowledge that does not require conceptual change. In this project, however, they are testing the hypothesis that executive function also underlies the ability to achieve conceptual change.

“For cognitive change, one needs to ‘think outside the box,’ look at things differently from the way one had been looking at them,” says Adele Diamond, one of the founders of the field of developmental cognitive neuroscience and an expert on executive function. “To get to that point, it helps to be able to try out different perspectives and experiment with looking at things this way and that.

“Playing with ideas, relating things in new ways relies heavily on working memory,” she says referencing one component of executive function examined in Carey’s and Zaitchik’s research project. Additionally, “to think in new ways, to see things in new ways, one needs to inhibit old ways of seeing things, old habits,” she notes referencing inhibitory control, which the project leaders are also examining.

Diamond is an outside project observer at the University of British Columbia in Vancouver, where she is the Tier 1 Canada Research Chair for Developmental Cognitive Neuroscience within the Psychiatry Department there.

Work by Diamond and her colleagues provides a backdrop for Carey’s and Zaitchik’s approach. In pioneering research, Diamond found school activities in early childhood–including play–could improve children’s executive function and better their performance on standard academic testing. Her research also shows executive function can be improved in 4-5 year olds, ages that some researchers had thought was too early to try to improve executive function.

Carey and Zaitchik are conducting several experiments that explore how executive function relates to conceptual change. They are interested in exploring the possibility that providing training to enhance executive function can also facilitate conceptual change. They are also exploring whether diminished executive functioning might explain science and math difficulties in children at risk for school failure. (For more information on these studies see the article titled “Unlocking the secrets of children’s complex thinking: the studies”)

They are testing the hypothesis that executive function underlies the ability to achieve conceptual change in two very different groups. The first group is children who are engaged in new learning of specific science and math theories. The second group is healthy elderly adults who, despite decades of experience holding and using the theories involved, nonetheless make many of the same errors in reasoning that children do.

“This work has the potential to support and promote executive function in children in ways that will have broad and deep impacts on their learning and achievement,” says Laura Namy, Developmental and Learning Sciences program director at NSF, pinning the research to important child development priorities.

Moreover, the research could have far-reaching importance to populations with particularly weak executive function, such as children with attention deficit hyperactivity disorder, a population also studied in the project, as well as disadvantaged children, aging adults and patients with Alzheimer’s disease.

“That executive function enhancement can directly impact a mental process so far downstream as conceptual reasoning is potentially extraordinarily transformative,” says Namy.

“It implies that a relatively straightforward intervention, such as executive function training, has the potential to ‘level the playing field’ for children from disadvantaged backgrounds, for those with attention deficits and those experiencing age- and disease-related cognitive decline.”

The relationship between executive function and conceptual change appears to be powerful, she says. “The goal of this investigation is to begin to discover why.”



Powering down at night will help young students power up during the day

From FMS Global News Desk of Jeanne Hambleton Released: 4-Sep-2014
Source Newsroom: Stony Brook University

STONY BROOK, NY, SEPTEMBER 5, 2014 – Sleep, or lack thereof, and technology often go hand in hand when it comes to school-aged kids. Nearly three out of four children (72%) between the ages of 6 and 17 have at least one electronic device in their bedrooms while sleeping, according to a National Sleep Foundation survey. Children who leave those electronic devices on at night sleep less—up to one hour less on average per night, according to a poll released by the foundation earlier this year.

Dr. Jill Creighton, Assistant Professor of Pediatrics, Stony Brook Children’s Hospital says the key to a successful school year starts with Z’s. So parents, how can you power down your kids at night and make bedtime easier? Dr. Creighton shares her tips.

“First – develop a nighttime routine,” says Dr. Creighton. Whether it is a bath, reading a book or listening to soothing music, these actives will have a better impact on your child to help them relax before going to sleep.

Second – Power off! “The hour before bed should be a no-electronics zone,” says Dr. Creighton. Studies show that the light from backlit electronics (like tablets, smartphones and video games) can disrupt our ability to fall—and stay—asleep. Dr. Creighton says designate a spot in your home for electronics to be plugged in, then have your kids start their bedtime routine by plugging in one hour before lights out.

Ban hand-held devices from the bedroom. “The burst of light from a phone (even if it is just to check the time) can break a sleep cycle,” says Dr. Creighton. “A regular alarm clock is best.”

If your child has a slight addiction to technology and is resistant about turning off their device, try dialing down the screen time. “Reduce screen time by 30 minutes or more each week until you reach your goal,” says Dr. Creighton.

“A good rule of thumb is try to limit recreational screen time to 60 minutes every day. And for every 30 minutes of screen time, make sure your kids get 30 minutes of physical activity.”

Try to replace screen time with an activity. “It is sometimes hard to get kids off the couch and get them moving, especially if they think of physical activity as “exercise’’ or “boring,” says Dr. Creighton. “Parents, get creative and make moving fun for kids.”

Some of Dr. Creighton’s ideas: a 20-minute family walk, 20 minutes of shooting hoops outside, walking the dog, going bike riding and doing chores (with the promise of an allowance) such as vacuuming, putting away laundry, raking leaves, shoveling snow and helping with the garbage/recycling, which are big favorites in her household.

Lastly, establish good habits. Being distracted by phones, hand-held devices and TV shows during mealtime cannot only lead to overeating, but additional unneeded screen time. And be a good role model. Parents, set a good example when it comes to screen time.
So how much sleep do your children need? General sleep guidelines from the National Heart, Lung and Blood Institute show that sleep time change as we age, but experts say there is no magic number for sleep, with individual needs varying.
• Newborns: 16-18 hours a day.
• Preschool-age children: 11-12 hours a day.
• School-age children: at least 10 hours a day.
• Teens: 9-10 hours a day.
• Adults (including the elderly): 7-8 hours a day.



Back tomorrow Jeanne





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