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University of Chicago Study Determines Certain Gut Bacteria Can Help Prevent Food Allergies and Other Gastrointestinal Illnesses

With further research, clinical laboratories may soon be performing macrobiotic testing to measure certain bacterial levels in patients’ gut bacteria

New insights from the University of Chicago (UChicago) into how human microbiota (aka, gut bacteria) play a role in food allergies has the potential to change the way a number of gastrointestinal health conditions are diagnosed and treated. This would give microbiologists and clinical laboratories a greater role in helping physicians diagnose, treat, and monitor patients with these health issues.

Past research has shown that certain gut bacteria can prevent antigens that trigger allergic reactions from entering the bloodstream. For example, Clostridium bacteria in the stomach produce a short-chain fatty acid known as butyrate, a metabolite that promotes the growth of healthy bacteria in the gut. This helps keep the microbiome in balance.

One way butyrate is created in the gut is through the fermentation of fiber. However, a lack of fiber in the diet can deplete the production of butyrate and cause the microbiome to be out of balance. When this happens, a state known as dysbiosis occurs that disrupts the microbiome and can lead to food allergies. 

Without butyrate, the gut lining can become permeable and allow food to leak out of the gastrointestinal tract and into the body’s circulatory system. This reaction can trigger a potentially fatal anaphylactic response in the form of a food allergy. Thus, eating enough fiber is critical to the production of butyrate and to maintaining a balanced microbiome.

But today’s western diet can be dangerously low in soluble fiber. Therefore, the scientists at the University of Chicago have developed “a special type of polymeric molecule to deliver a crucial metabolite produced by these bacteria directly to the gut, where it helps restore the intestinal lining and allows the beneficial bacteria to flourish. … these polymers, called micelles, can be designed to release a payload of butyrate, a molecule that is known to help prevent food allergies, directly in the small and large intestines,” according to a UChicago news release.

This will be of interest to microbiologists, in particular. It’s another example of researchers connecting a specific species of bacteria in the human microbiome to a specific benefit.

The University of Chicago scientists published their findings in the journal Nature Biomedical Engineering titled, “Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles.”

Cathryn Nagler, PhD

“It’s very unlikely that butyrate is the only relevant metabolite, but the beauty of this platform is that we can make polymers with other microbial metabolites that could be administered in conjunction with butyrate or other therapies,” said Cathryn Nagler, PhD (above), Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at UChicago and a senior author of the study. “So, the potential for the polymer platform is pretty much wide open.” As further research validates these findings, clinical labs are likely to be doing microbiomic testing to monitor these therapies. (Photo copyright: University of Chicago.)

Restoring Butyrate in the Gut

One way to treat this anomaly has been through a microbiota transplant—also called a fecal biota transplant—where the administration of a solution of fecal matter is transplanted from a donor into the intestinal tract of the recipient. This transplant alters the recipient’s gut microbial composition to a healthier state, but it has had mixed results. 

So, the UChicago researchers went in another direction (literally). They created an oral solution of butyrate and administered it to mice in the lab. The purpose of the solution was to thwart an allergic reaction when the mice were exposed to peanuts. 

But there was a problem with their oral solution. It was repulsive.

“Butyrate has a very bad smell, like dog poop and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it,” Shijie Cao, PhD, Postdoctoral Scientist at the Pritzker School of Molecular Engineering at UChicago and one of the researchers who worked on the project, told Medical News Today.

The researchers developed a new configuration of polymers that masked the butyrate. They then delivered these polymer micelles directly into the digestive systems of mice that lacked healthy gut bacteria or a proper gut linings.

The treatment restored the microbiome by increasing the production of peptides that obliterate harmful bacteria. This allowed more of the beneficial butyrate-producing bacteria to emerge, which protected the mice from an anaphylactic reaction to peanuts and even reduced the symptom severity in an ulcerative colitis model. 

“We were delighted to see that our drug both replenished the levels of butyrate present in the gut and helped the population of butyrate-producing bacteria to expand,” said Cathryn Nagler, PhD, Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at the University of Chicago and a senior author of the study, in the press release. “That will likely have implications not only for food allergy and inflammatory bowel disease (IBD), but also for the whole set of non-communicable chronic diseases that have been rising over the last 30 years, in response to lifestyle changes and overuse of antibiotics in our society.”

Future Benefits of UChicago Treatment

According to data from the Asthma and Allergy Foundation of America, about 20 million Americans suffered from food allergies in 2021. This includes approximately 16 million (6.2%) of adults and four million (5.8%) of children. The most common allergens for adults are shellfish, peanuts, and tree nuts, while the most common allergens for children are milk, eggs, and peanuts. 

The best way to prevent an allergic reaction to a trigger food is strict avoidance. But this can be difficult to ensure outside of the home. Therefore, scientists are searching for ways to prevent food allergies from happening in the first place. The micelle technology could be adapted to deliver other metabolites and molecules which may make it a potential platform for treating allergies as well as other inflammatory gastrointestinal diseases

“It’s a very flexible chemistry that allows us to target different parts of the gut,” said Jeffrey Hubbell, PhD, Eugene Bell Professor in Tissue Engineering and Vice Dean and Executive Officer at UChicago’s Pritzker School of Molecular Engineering and one of the project’s principal investigators, in the UChicago news release. “And because we’re delivering a metabolite like butyrate, it’s antigen-agnostic. It’s one agent for many different allergic indications, such as peanut or milk allergies. Once we begin working on clinical trials, that will be a huge benefit.”

Nagler and Hubbell have co-founded a company called ClostraBio to further the development of butyrate micelles into a commercially available treatment for peanut and other food allergies. They hope to begin clinical trials within the next 18 months and expand the technology to other applications as well.  

Further research and clinical trials are needed to prove the validity of using polymer micelles in the treatment of diseases. But it is possible that clinical laboratories will be performing microbiomic testing in the future to help alleviate allergic reactions to food and other substances.

—JP Schlingman

Related Information:

Peanut and Food Allergies May Be Reversed with Compound Produced by Healthy Gut Bacteria

Time Release Polymers Deliver Metabolites to Treat Peanut Allergy and Colitis

Food Allergies: Reversing the Old, Preventing the New with Gut Bacteria

Scientists Reverse Food Allergies by Targeting the Microbiome

Polymers Help Protect Mice from Anaphylactic Reaction to Peanuts, UChicago Research Finds

Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles

Binghamton University Scientists Develop Biobattery That Powers Ingestible Devices and Biosensors Inside the Human Small Intestine

Biobattery might one day power clinical laboratory testing devices designed to function in vivo to measure and wirelessly report certain biomarkers

Clinical laboratories may one day regularly process biomarker data sent by ingested medical devices from inside the human body, such as the colon and intestines. But powering such devices remains a challenge for developers. Now, researchers at Binghamton University in New York have developed a biobattery that derives its power based on pH reactions when it comes in contact with acids inside the gut.

The battery uses “bacteria to create low levels of electricity that can power sensors and Wi-Fi connections as part of the Internet of Things,” according to a Binghamton University news release.

The biobattery uses microbial fuel cells with spore-forming bacteria for power and it remains inactive until it reaches the small intestine.

Ingestible devices, such as wireless micro cameras, are being utilized more frequently to investigate a myriad of activities that occur in vivo. But traditional batteries that power ingestible diagnostic gadgets can be potentially harmful and are less reliable.

In addition, the small intestine in humans is typically between 10 and 18 feet in length and it folds several times to fit the abdomen. Thus, the inside area can be very difficult to reach for diagnostic purposes.

The scientists published their research in the journal Advanced Energy Materials titled, “A Biobattery Capsule for Ingestible Electronics in the Small Intestine: Biopower Production from Intestinal Fluids Activated Germination of Exoelectrogenic Bacterial Endospores.”

Seokheun “Sean” Choi, PhD

“There are some regions in the small intestine that are not reachable, and that is why ingestible cameras have been developed to solve this issue,” said Seokheun “Sean” Choi, PhD (above), Professor of Electrical and Computer Engineering at Binghamton University, in a news release. “They can do many things, such as imaging and physical sensing, even drug delivery. The problem is power. So far, the electronics are using primary batteries that have a finite energy budget and cannot function for the long term.” As these technologies develop, clinical laboratories may play a role in collecting biomarker data from these devices interpretation by physicians. (Photo copyright: Binghamton University/Jonathan Cohen.)

How Binghamton Researchers Developed Their Biobattery

To develop their new biobattery, the Binghamton researchers encased Bacillus subtilis, a bacterium found in the gastrointestinal tract of humans, in a graphene integrated hydrogel that excels at grabbing moisture from the air.

The dime-sized fuel cell assembly is then sealed with a piece of Kapton tape, which can withstand temperatures from -500 to 750 degrees Fahrenheit. When the tape is removed, moisture mixes with a chemical germinant that causes the bacteria to begin manufacturing spores. 

“We use these spores as a dormant, storable biocatalyst,” explained Seokheun “Sean” Choi, PhD, Professor of Electrical and Computer Engineering at Thomas J. Watson College of Engineering and Applied Science, Binghamton University, in the news release. “The spores can be germinated when the nutrients are available, and they can resume vegetative life and generate the power.”

The biobattery generates around 100 microwatts per square centimeter of power density, but it can take up to an hour to germinate completely. After one hour, the energy generated from the device can power an LED light, a small clock, or a digital hygrometer, as well as a micro camera for in vivo use.

“We wanted to make these bio-batteries for portable, storable, and on-demand power generation capabilities,” Choi said in the news release.

“The problem is, how can we provide the long-term storage of bacteria until used? And if that is possible, then how would you provide on-demand battery activation for rapid and easy power generation? And how would you improve the power?” Choi added.

Heating the fuel cell decreased the time it took to reach full power to 20 minutes, and increasing the humidity resulted in higher electrical output.

Potential for Long-term Power Storage

In addition, after a week of being stored at room temperature, the activated battery had only lost 2% of its power. The researchers also believe that the device could function properly in an inactivate state for up to 100 years, provided there is enough moisture to activate the bacteria after the Kapton tape is removed.

“The overall objective is to develop a microbial fuel cell that can be stored for a relatively long period without degradation of bio-catalytic activity, and also can be rapidly activated by absorbing moisture from the air,” said Choi in the news release. 

The federal Office of Naval Research funded the study.

More research and studies are needed to confirm the biobattery performs properly and is feasible for general use. This experimentation would require both animal and human testing, along with biocompatibility studies.

“I think this is a good start,” Choi added. “Hopefully, we can make a commercial product using these ideas.”

If the biobattery can power an ingestible medical device for a reasonable period of time, then this invention may be able to power a clinical laboratory testing device that could function in vivo to measure and wirelessly report certain biomarkers inside the body. 

—JP Schlingman

Related Information:

Tiny Biobattery with 100-year Shelf Life Runs on Bacteria

Capsule-Sized Ingestible Biobatteries Could Allow New View of Digestive System

Bacteria-based Biobattery Could Power Devices in the Small Intestine

A Biobattery Capsule for Ingestible Electronics in the Small Intestine: Biopower Production from Intestinal Fluids Activated Germination of Exoelectrogenic Bacterial Endospores

Spore-producing Bacteria Battery Could Last 100 Years on the Shelf

Scientists Create Stretchable Battery Made Entirely Out of Fabric

University of Colorado Researchers Develop Miniature Colonoscopy Robot Capable of Collecting Biopsies and Transmit Diagnostic Information in Real Time

GI pathologists will be interested in how the Endoculus device uses tank-like treads to traverse the gastrointestinal tract, where it can capture images and perform biopsies

Gastroenterologists (GI) may soon gain a useful new tool for use in gathering both biopsies and diagnostic information when examining the gastrointestinal tract. Ongoing development of a new robotic device promises both capabilities using technology that will be of interest to GI pathologists and clinical laboratory scientists.

Researchers at the University of Colorado Boulder’s Advanced Medical Technologies Laboratory (AMTL) have developed a capsule-sized robotic device called “Endoculus” which they believe could eventually replace traditional endoscopes used in colonoscopies and endoscopies.

The minute robotic device uses tank-like treads to traverse the colon. While there, it can capture live images and perform biopsies under the control of a gastroenterologist. The researchers believe the robotic technology will benefit GIs performing the colonoscopies as well as the pathologists called upon to analyze biopsies.

Gregory Formosa, PhD

“Currently, endoscopy consists of a gastroenterologist using a semi-rigid, long rope-like device and endoscope to propel through your colon manually,” Gregory Formosa, PhD (above) a member of the AMTL team that developed Endoculus, said in a YouTube video describing the device. “We think that a robotic capsule endoscope can replace conventional endoscopes by making them faster, safer, and more robust than a human operator can do currently with traditional techniques,” he added. (Photo copyright: University of Colorado.)

AMTL researcher Gregory Formosa, PhD, said the team’s goal is to “have a capsule-sized robot that can actively traverse [a patient’s] entire gastrointestinal tract and send out diagnostics in real time, as well as autonomously navigate itself to localize problematic areas within [the] intestinal tract.”

Formosa noted that colorectal cancer is “the third-most fatal and diagnosed cancer in the United States.” But if caught at an early stage, these cancers are “95% treatable,” he added. “So, if we can get people screened early, we definitely can reduce the fatality rate of colorectal cancers significantly.”

The AMTL research team, now led by mechanical engineering professor Mark Rentschler, PhD, described an early prototype of the device in a Surgical Endoscopy paper, titled, “Surgical Evaluation of a Novel Tethered Robotic Capsule Endoscope Using Micro-Patterned Treads.” The researchers have since followed that with additional papers in IEEE journals and presentations at the IEEE International Conference on Intelligent Robots and Systems.

The Endoculus device

Currently about the size of a C battery, Endoculus (above) is a “fully packed medical device, complete with a camera, an air pump for inflating the colon, a water pump for cleaning, and a tool port for holding biopsy snares,” states a University of Colorado news story, titled, “A Robot May One Day Perform Your Colonoscopy.” (Photo copyright: University of Colorado.)

How Endoculus Works

One key to the device are the four treads, which are designed for traction on digestive tissue.

“You have to forget about everything you know from a locomotion standpoint because driving around inside the body is very different than driving around in a car,” said Rentschler in the University of Colorado news story. “The environment is highly deformable. It’s very slick. There are sharp peaks that you have to go over.”

The university news story noted the current availability of ingestible “pill cams” that can take photos as they travel through the digestive system. But once swallowed, their movements cannot be controlled.

“For our robots to be able to reach those regions that [can be] reached with a pill-cam—but also be able to stop and look around—that could be a big paradigm shift in the way we view these procedures,” said Micah Prendergast, PhD, an AMTL research team member.

Could Biopsies Be Diagnosed In Situ with Endoculus?

The researchers currently view Endoculus as a potentially better way to perform conventional biopsies. But could it lead to bigger advancements?

“Researchers continue to develop devices to help various specialist physicians—in this case GIs—do more when treating patients,” said Dark Daily Publisher and Editor-in-Chief Robert Michel. “This device fits that description. It is designed to improve the ability of GIs to evaluate the colon. Not only does this device do that, but it can also collect a biopsy at sites of interest. In this way, it is a device that can be a benefit to pathologists who will analyze the biopsy.

“With improvements in digital cameras and associated AI-powered analytical tools, the day might not be far off when a device like this can use the camera and artificial intelligence to diagnose the tissue of interest in situ,” he added. “This might create the opportunity for pathologists to be present in the exam room during the procedure, or even viewing the images remotely.

“Not only would that eliminate the need to collect a tissue specimen that must then be sent to a pathology lab, but it would create a new opportunity for pathologists to add value to patient care while shortening the time to diagnosis for the tissue of interest during these procedures,” Michel noted.

         

Stephen Beale

Related Information:

Colon Explorer for Automatic Imaging and Biopsying of Polyps

This Tiny Robot Tank Could One Day Help Doctors Explore Your Intestine

A Robot May One Day Perform Your Colonoscopy

University of Utah and Sloan Kettering Institute Study Sheds Light on How the Body Recognizes “Good” from Bad Bacteria in the Microbiome

Researchers found that early in life intestinal microorganisms “educate” the thymus to develop T cells; findings could lead to improved immune system therapeutics and associated clinical laboratory tests

Researchers at the University of Utah and the Sloan Kettering Institute (SKI)—the experimental research division of the Memorial Sloan Kettering Cancer Center (MSKCC) in New York—have uncovered new insights into how the immune system learns to distinguish between harmful infectious bacteria and “good” bacteria in the microbiome that occupies the gastrointestinal tract.

The researchers published their findings in Nature. They used engineered mice as the test subjects and say the study could lead to a greater understanding of human conditions such as Type 1 and Type 2 diabetes and inflammatory bowel disease (IBD). In turn, this new knowledge could lead to new diagnostic tests for clinical laboratories.

“From the time we are born, our immune system is set up so that it can learn as much as it can to distinguish the good from the bad,” Matthew Bettini, PhD, Associate Professor of Pathology said in a University of Utah news release.

Does Gut Bacteria ‘Educate’ the Immune System?

The researchers were attempting to learn how the body develops T cells specific to intestinal microorganisms. T cells, they noted, are “educated” in the thymus, an organ in the upper chest that is key to the adaptive immune system.

“Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection,” they wrote in their study. “Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen, while limiting inflammatory anti-commensal responses.”

Matthew Bettini, PhD and Gretchen Diehl, PhD

Matthew Bettini, PhD (left), Associate Professor of Pathology at the University of Utah, co-authored the study along with Gretchen Diehl, PhD (right), an immunologist at Sloan Kettering Institute. The team also included researchers from the Baylor College of Medicine in Houston and the Washington University School of Medicine in St. Louis. “Our studies make clear that there is a window in which gut microbiota have access to the immune education process. This opens up possibilities for designing therapeutics that can influence the trajectory of the immune system during this early time point,” Bettini said in the University of Utah news release. (Photo copyright: University of Utah/Sloan Kettering Institute.)

Findings Challenge Earlier Assumptions about Microbiota’s Influence on Immunity

The researchers began by seeding the intestines of mice with segmented filamentous bacteria (SFB), which they described as “one of the few commensal microorganisms for which a microorganism-specific T-cell receptor has been identified.” In addition, SFB-specific T cells can be tracked using a magnetic enrichment technique, they wrote in Nature.

They discovered that in young mice, microbial antigens from the intestines migrated to the thymus, resulting in an expansion of T cells specific to SFB. But they did not see an expansion of T cells in adult mice, suggesting that the process of adapting to microbiota happens early.

“Our study challenges previous assumptions that potential pathogens have no influence on immune cells that are developing in the thymus,” Bettini said in the news release. “Instead, we see that there is a window of opportunity for the thymus to learn from these bacteria. Even though these events that shape which T cells are present happen early in life, they can have a greater impact later in life.”

For example, T cells specific to microbiota can also protect against closely related harmful bacteria, the researchers found. “Mice populated with E. coli at a young age were more than six times as likely to survive a lethal dose of Salmonella later in life,” the news release noted. “The results suggest that building immunity to microbiota also builds protection against harmful bacteria the body has yet to encounter.”

According to the researchers, in addition to protecting against pathogens, “microbiota-specific T cells have pathogenic potential.” For example, “defects in these mechanisms could help explain why the immune system sometimes attacks good bacteria in the wrong place, causing the chronic inflammation that’s responsible for inflammatory bowel disease,” they suggested.

Other Clinical Laboratory Research into the Human Microbiome

The research conducted by the University of Utah, Sloan Kettering Institute, and others, adds to a growing understanding of the human microbiome. For example, in “International Study into Ancient Poop Yields Insight into the Human Microbiome, May Produce Useful Insights for Microbiologists,” Dark Daily reported on an international study of 2000-year-old human feces which suggested that the microbiomes of today’s humans may have been modified by modern phenomena such as processed food and sanitation.

And in “Harvard Medical School Study Finds ‘Staggering’ Amounts of Genetic Diversity in Human Microbiome; Might Be Useful in Diagnostics and Precision Medicine,” Dark Daily reported on a study from Harvard Medical School and Joslin Diabetes Center that unveiled a “staggering microbial gene diversity” in the microbiome and the potential for identification of more-useful biomarkers for disease detection.

And a study from the University of Nebraska-Lincoln and the Ocean Road Cancer Institute in Tanzania raised the possibility that bacteria in the cervical microbiome could lead to new tests for cervical cancer. (See Dark Daily, “University Study Suggests Cervical Microbiome Could Be Used by Medical Laboratories as Biomarker in Determining Women’s Risk for Cervical Cancer.”

All of this suggests the potential in the future “for clinical laboratories and microbiologists to do microbiome testing in support of clinical care,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report. Of course, more research is needed in these areas.

“We believe that our findings may be extended to areas of research where certain bacteria have been found to be either protective or pathogenic for other conditions, such as Type 1 and Type 2 diabetes,” Bettini said in the University of Utah news release. “Now we’re wondering, will this window of bacterial exposure and T cell development also be important in initiating these diseases?”

—Stephen Beale

Related Information

How the Body Builds a Healthy Relationship With ‘Good’ Gut Bacteria

Thymic Development of Gut-Microbiota-Specific T Cells

International Study into Ancient Poop Yields Insight into the Human Microbiome, May Produce Useful Insights for Microbiologists

Harvard Medical School Study Finds ‘Staggering’ Amounts of Genetic Diversity in Human Microbiome; Might Be Useful in Diagnostics and Precision Medicine

University Study Suggests Cervical Microbiome Could Be Used by Medical Laboratories as Biomarker in Determining Women’s Risk for Cervical Cancer

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