New therapy targets gut bacteria to prevent and reverse food allergies

New therapy targets gut bacteria to prevent and reverse food allergies

A new study identifies the species of bacteria in the human infant gut that protect against food allergies, finding changes associated with the development of food allergies and an altered immune response.

Every three minutes, a food-related allergic reaction sends someone to the emergency room in the U.S. Currently, the only way to prevent a reaction is for people with food allergies to completely avoid the food to which they are allergic. Researchers are actively seeking new treatments to prevent or reverse food allergies in patients. Recent insights about the microbiome -- the complex ecosystem of microorganisms that live in the gut and other body sites -- have suggested that an altered gut microbiome may play a pivotal role in the development of food allergies. A new study, led by investigators from Brigham and Women's Hospital and Boston Children's Hospital, identifies the species of bacteria in the human infant gut that protect against food allergies, finding changes associated with the development of food allergies and an altered immune response. In preclinical studies in a mouse model of food allergy, the team found that giving an enriched oral formulation of five or six species of bacteria found in the human gut protected against food allergies and reversed established disease by reinforcing tolerance of food allergens. The team's results are published in Nature Medicine.

"This represents a sea change in our approach to therapeutics for food allergies," said co-senior author Lynn Bry, MD, PhD, director of the Massachusetts Host-Microbiome Center at the Brigham. "We've identified the microbes that are associated with protection and ones that are associated with food allergies in patients. If we administer defined consortia representing the protective microbes as a therapeutic, not only can we prevent food allergies from happening, but we can reverse existing food allergies in preclinical models. With these microbes, we are resetting the immune system."

The research team conducted studies in both humans and preclinical models to understand the key bacterial species involved in food allergies. The team repeatedly collected fecal samples every four to six months from 56 infants who developed food allergies, finding many differences when comparing their microbiota to 98 infants who did not develop food allergies. Fecal microbiota samples from infants with or without food allergies were transplanted into mice who were sensitized to eggs. Mice who received microbiota from healthy controls were more protected against egg allergy than those who received microbiota from the infants with food allergies.

Using computational approaches, researchers analyzed differences in the microbes of children with food allergies compared to those without in order to identify microbes associated with protection or food allergies in patients. The team tested to see if orally administering protective microbes to mice could prevent the development of food allergies. They developed two consortia of bacteria that were protective. Two separate consortia of five or six species of bacteria derived from the human gut that belong to species within the Clostridiales or the Bacteroidetes could suppress food allergies in the mouse model, fully protecting the mice and keeping them resistant to egg allergy. Giving other species of bacteria did not provide protection.

"It's very complicated to look at all of the microbes in the gut and make sense of what they may be doing in food allergy, but by using computational approaches, we were able to narrow in on a specific group of microbes that are associated with a protective effect," said co-first author Georg Gerber, MD, PhD, MPH, co-director of the Massachusetts Host-Microbiome Center and chief of the Division of Computational Pathology in the Department of Pathology at the Brigham. "Being able to drill down from hundreds of microbial species to just five or six or so has implications for therapeutics and, from a basic science perspective, means that we can start to figure out how these specific bacteria are conferring protection."

To understand how the bacteria species might be influencing food allergy susceptibility, the team also looked at immunological changes, both in the human infants and in mice. They found that the Clostridiales and Bacteroidetes consortia targeted two important immunological pathways and stimulated specific regulatory T cells, a class of cells that modulate the immune system, changing their profile to promote tolerant responses instead of allergic responses. These effects were found both in the pre-clinical models and also found to occur in human infants.

The new approach represents a marked contrast to oral immunotherapy, a strategy that aims to increase the threshold for triggering an allergic reaction by giving an individual small but increasing amounts of a food allergen. Unlike this approach, the bacteriotherapy changes the immune system's wiring in an allergen-independent fashion, with potential to broadly treat food allergies rather than desensitizing an individual to a specific allergen.

"When you can get down to a mechanistic understanding of what microbes, microbial products, and targets on the patient side are involved, not only are you doing great science, but it also opens up the opportunity for finding a better therapeutic and a better diagnostic approach to disease. With food allergies, this has given us a credible therapeutic that we can now take forward for patient care," said Bry.

Bry and Gerber, along with senior author Talal Chatila, MD, of Boston Children's Hospital, are founders and have equity in ConsortiaTX, a company that is developing a live human biotherapeutic product (CTX-944). (Co-senior author Rima Rachid, MD, of Boston Children's Hospital, also has equity in the company.) ConsortiaTX is preparing for a Phase 1b trial in pediatric food allergy, followed by expansion into additional allergic diseases. ConsortiaTX has obtained an exclusive global license to the intellectual property related to the microbial discoveries published in the Nature Medicine paper.

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Materials provided by Brigham and Women's Hospital. Note: Content may be edited for style and length.

Researchers discover brain circuit linked to food impulsivity

Eating popcorn at a movie (stock image).

Credit: © Zoriana / Adobe Stock

You're on a diet, but the aroma of popcorn in the movie theater lobby triggers a seemingly irresistible craving.

Within seconds, you've ordered a tub of the stuff and have eaten several handfuls.

Impulsivity, or responding without thinking about the consequences of an action, has been linked to excessive food intake, binge eating, weight gain and obesity, along with several psychiatric disorders including drug addiction and excessive gambling.

A team of researchers that includes a faculty member at the University of Georgia has now identified a specific circuit in the brain that alters food impulsivity, creating the possibility scientists can someday develop therapeutics to address overeating.

The team's findings were published recently in the journal Nature Communications.

"There's underlying physiology in your brain that is regulating your capacity to say no to (impulsive eating)," said Emily Noble, an assistant professor in the UGA College of Family and Consumer Sciences who served as lead author on the paper. "In experimental models, you can activate that circuitry and get a specific behavioral response."

Using a rat model, researchers focused on a subset of brain cells that produce a type of transmitter in the hypothalamus called melanin concentrating hormone (MCH).

While previous research has shown that elevating MCH levels in the brain can increase food intake, this study is the first to show that MCH also plays a role in impulsive behavior, Noble said.

"We found that when we activate the cells in the brain that produce MCH, animals become more impulsive in their behavior around food," Noble said.

To test impulsivity, researchers trained rats to press a lever to receive a "delicious, high-fat, high-sugar" pellet, Noble said. However, the rat had to wait 20 seconds between lever presses. If the rat pressed the lever too soon, it had to wait an additional 20 seconds.

Researchers then used advanced techniques to activate a specific MCH neural pathway from the hypothalamus to the hippocampus, a part of the brain involved with learning and memory function.

Results indicated MCH doesn't affect how much the animals liked the food or how hard they were willing to work for the food. Rather, the circuit acted on the animals' inhibitory control, or their ability to stop themselves from trying to get the food."Activating this specific pathway of MCH neurons increased impulsive behavior without affecting normal eating for caloric need or motivation to consume delicious food," Noble said. "Understanding that this circuit, which selectively affects food impulsivity, exists opens the door to the possibility that one day we might be able to develop therapeutics for overeating that help people stick to a diet without reducing normal appetite or making delicious foods less delicious."

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Story Source:

Materials provided by University of Georgia. Original written by Cal Powell. Note: Content may be edited for style and length.

Researchers discover brain circuit linked to food impulsivity

Eating popcorn at a movie 

You're on a diet, but the aroma of popcorn in the movie theater lobby triggers a seemingly irresistible craving.

Within seconds, you've ordered a tub of the stuff and have eaten several handfuls.

Impulsivity, or responding without thinking about the consequences of an action, has been linked to excessive food intake, binge eating, weight gain and obesity, along with several psychiatric disorders including drug addiction and excessive gambling.

A team of researchers that includes a faculty member at the University of Georgia has now identified a specific circuit in the brain that alters food impulsivity, creating the possibility scientists can someday develop therapeutics to address overeating.

The team's findings were published recently in the journal Nature Communications.

"There's underlying physiology in your brain that is regulating your capacity to say no to (impulsive eating)," said Emily Noble, an assistant professor in the UGA College of Family and Consumer Sciences who served as lead author on the paper. "In experimental models, you can activate that circuitry and get a specific behavioral response."

Using a rat model, researchers focused on a subset of brain cells that produce a type of transmitter in the hypothalamus called melanin concentrating hormone (MCH).

While previous research has shown that elevating MCH levels in the brain can increase food intake, this study is the first to show that MCH also plays a role in impulsive behavior, Noble said.

"We found that when we activate the cells in the brain that produce MCH, animals become more impulsive in their behavior around food," Noble said.

To test impulsivity, researchers trained rats to press a lever to receive a "delicious, high-fat, high-sugar" pellet, Noble said. However, the rat had to wait 20 seconds between lever presses. If the rat pressed the lever too soon, it had to wait an additional 20 seconds.

Researchers then used advanced techniques to activate a specific MCH neural pathway from the hypothalamus to the hippocampus, a part of the brain involved with learning and memory function.

Results indicated MCH doesn't affect how much the animals liked the food or how hard they were willing to work for the food. Rather, the circuit acted on the animals' inhibitory control, or their ability to stop themselves from trying to get the food."Activating this specific pathway of MCH neurons increased impulsive behavior without affecting normal eating for caloric need or motivation to consume delicious food," Noble said. "Understanding that this circuit, which selectively affects food impulsivity, exists opens the door to the possibility that one day we might be able to develop therapeutics for overeating that help people stick to a diet without reducing normal appetite or making delicious foods less delicious."

---

Story Source:

Materials provided by University of Georgia. Original written by Cal Powell. Note: Content may be edited for style and length.

Experts unlock key to photosynthesis, a find that could help us meet food security demands

Green leaf in sunlight

Scientists have solved the structure of one of the key components of photosynthesis, a discovery that could lead to photosynthesis being 'redesigned' to achieve higher yields and meet urgent food security needs.

The study, led by the University of Sheffield and published today in the journal Nature, reveals the structure of cytochrome b6f -- the protein complex that significantly influences plant growth via photosynthesis.

Photosynthesis is the foundation of life on Earth providing the food, oxygen and energy that sustains the biosphere and human civilisation.

Using a high-resolution structural model, the team found that the protein complex provides the electrical connection between the two light-powered chlorophyll-proteins (Photosystems I and II) found in the plant cell chloroplast that convert sunlight into chemical energy.

Lorna Malone, the first author of the study and a PhD student in the University of Sheffield's Department of Molecular Biology and Biotechnology, said: "Our study provides important new insights into how cytochrome b6f utilises the electrical current passing through it to power up a 'proton battery'. This stored energy can then be then used to make ATP, the energy currency of living cells. Ultimately this reaction provides the energy that plants need to turn carbon dioxide into the carbohydrates and biomass that sustain the global food chain."

The high-resolution structural model, determined using single-particle cryo-electron microscopy, reveals new details of the additional role of cytochrome b6f as a sensor to tune photosynthetic efficiency in response to ever-changing environmental conditions. This response mechanism protects the plant from damage during exposure to harsh conditions such as drought or excess light.

Dr Matt Johnson, reader in Biochemistry at the University of Sheffield and one of the supervisors of the study added: "Cytochrome b6f is the beating heart of photosynthesis which plays a crucial role in regulating photosynthetic efficiency.

"Previous studies have shown that by manipulating the levels of this complex we can grow bigger and better plants. With the new insights we have obtained from our structure we can hope to rationally redesign photosynthesis in crop plants to achieve the higher yields we urgently need to sustain a projected global population of 9-10 billion by 2050."

The research was conducted in collaboration with the Astbury Centre for Structural Molecular Biology at the University of Leeds.

Researchers now aim to establish how cytochrome b6f is controlled by a myriad of regulatory proteins and how these regulators affect the function of this complex.