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Showing posts with label Science. Show all posts
Showing posts with label Science. Show all posts

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.


How is the Organ 3D printing done? How far is it from transplanting the human body? What you want to know is here.

Experts: Hang Fei, National Human Body Tissue Functional Reconstruction Engineering Technology Research Center, South China University of Technology, Associate Professor, School of Materials Science and Engineering, South China University of Technology

3D printing, one of the most watched technologies since the 20th century, is undoubtedly the endorsement of advanced technology.

In recent years, with the development of 3D printing technology, this advanced technology has gradually penetrated into the medical field.

For example, the world's first 3D printed "complete heart" , born in April, has a cherry-sized heart of cells, blood vessels, ventricles and atrium.

There are also breakthrough studies in the past on 3D printing organs:

Solving the shortage of living organs and reducing the rejection of receptors is of great significance for organ transplantation.

So, how far away is the 3D printing organ to replace the donated organ for healing? Let's talk about it today.

What is 3D printing technology? 

"3D printing" is a popular name for the material forming process of "additive manufacturing".

3D printing is different from the traditional material forming process. In the process of processing, the material quality is not reduced, and it is formed by the accumulation of “bottom-up” materials, and gradually builds up like a house.

The whole process is based on digital model files and is realized by computer control, which can build complex structures that are difficult to manufacture in traditional processes.

It has been more than 30 years since the birth of the world's first commercial 3D printer. With the advancement of technology, 3D printing has become more and more connected with our lives.

Early 3D printing was only able to print with plastic as "ink."

Now, "ink" can be plastic, metal, ceramic, or even cells, and is injected into the "ink cartridge" for operation.

3D printing technology has three main types according to the process characteristics:

One is to use a high-energy beam such as a laser or a plasma beam to melt, sinter, and finally form metal, ceramic, and plastic powder layer by point.

This type of process is mainly used in the field of industrial processing. For example, some large-size titanium alloy parts of the domestic large aircraft C919 are printed by such a process.

The second type is to melt a material such as plastic into a flowing melt by heating, or to form a flowable slurry, which is extruded from a needle tip by pressure and solidified in a space.

Most of the common desktop 3D printers currently use this type of technology. Cell and organ printing is also often used in such processes.

The third type is based on the principle of photocuring, and the phenomenon that the ultraviolet curable resin causes the liquid of the photocurable resin to be cured is printed. Due to the high precision of laser focusing, such processes tend to have better forming accuracy. 

How does 3D printing print organs? 

It is the imagination of our ancestors to make a living, and the 3D printing of living cells is a real attempt.

Scientists in the fields of biomaterials and regenerative medicine are constantly trying to use 3D printing to make tissues and organs that can be implanted into the human body. 

This is also one of the most important emerging areas of 3D printing, and has been reported in recent years.

In 2016, scientists transplanted 3D printed tissue into living organisms and proved that the tissue that was born from the printer survived and grew like normal tissue. 

So how do these "organizations" and "organs" are created by 3D printing?
First, we need to design a digital model blueprint, and the cells, like the slurry in a regular desktop printer, are squeezed out of the needle and built layer by layer like a house to form a predetermined shape.
However, if there is no bond between the cells and the cells, they will collapse once printed. Therefore, a substance called a hydrogel is used as a scaffold to assemble the cells.
In the process of printing, the hydrogel can maintain the shape of the tissue or organ, and the cells are wrapped, bonded, and stacked in an orderly manner. Hydrogels can be biodegraded without biotoxicity. 

Natural tissue has a large number of tubing structures for a variety of fluids, such as blood, to flow through the tissue. If the printed tissue or organ does not have a duct cavity, the cell cannot survive.

Therefore, a part of the cavity is reserved in the hydrogel scaffold to facilitate initial feeding and metabolism.

When the cells survive and form a relatively stable structure, the hydrogel scaffold is degraded and further forms a "cavity" for the growth and development of tubes such as blood vessels. 

In this way, the "ink cartridge" of a typical "bio 3D printer" will be filled with biological "ink" composed of cells and hydrogels. During the printing process, the biological "ink" will be stacked layer by layer into the shape of the corresponding tissue. 

What is the difference between 3D printed organs and human organs?

At present, the tissues and organs manufactured by 3D printing in the laboratory are different from human organs in terms of size, structure, cell type, cell survival time, etc., so most of the 3D printed tissues and organs are still Not able to be implanted into the body as a transplant organ.

The 3D printed organ has been able to maintain a fixed shape with simple organ function.

However, human organs are often composed of a variety of different cells, and various types of cells or collections of cells play different roles. The organs also have a large number of structures such as blood vessels, nerves, and various types of tubes that together with the cells realize complex functions in the body.

Nowadays, 3D printed tissues or organs tend to have a single cell type, do not have a complex pipe network structure, and usually cannot realize the complex functions of human organs, and can only be called "like tissues" or "organs."

3D printed organs are used as tools for medical research in drug screening and tumor models.

For regenerative medicine, 3D printing uses cells from the recipient, the tissues and organs produced are not immune to rejection, and the size and function of tissues and organs can be highly customized.

3D printing of implantable organs has broad prospects in the near future and is highly anticipated. 

Source: Science China

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