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.
“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.
“On-a-chip” devices continue to advance and medical laboratories will be natural repositories for patient data as the technology continues to improve
Dark Daily has predicted that the future of clinical laboratory testing will include highly complex multi-analyte test panels. The biomarkers, however, could number in the hundreds or thousands. So, it’s interesting to see new research by a Massachusetts Institute of Technology (MIT) team currently developing a multi-biomarker organ test device for clinical purposes.
Motivated by the costly failure of animal testing efforts to develop drug safety and efficacy in humans, the MIT research engineers created a microfluidic platform technology they dubbed “physiome-on-a-chip,” or more colloquially, “body-on-a-chip.” Their goal is to identify drug reaction in different cell groups within the body (in vivo).
They acknowledged contributions of in vitro microphysiological systems (MPSs), AKA “organ-on-a-chip” (OOC) systems. They note, however, in their paper published in Scientific Reports, that more complex systems that interconnect and receive data from multiple MPSs are needed due to increasing limitations arising from drugs’ “lack of efficacy” rather than toxicity.
“Here we describe the development and implementation of multi-MPS platforms, AKA physiome-on-a-chip, supporting four-way, seven-way, and 10-way MPS interactions for several weeks,” the MIT engineers wrote.
Though MIT’s new technology needs further research and development time, as well as clinical trials, this type of chip design and its ability to scale is a positive development and progress toward Dark Daily’s prediction. Once finalized, it could be adopted in medical laboratories for many types of diagnostic testing purposes.
Researchers Motivated to Improve Drug Efficacy
According to an MIT news release, “MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.”
The “body-on-a-chip” technology, MIT says, is aimed at determining how drugs may affect one organ while also having side effects on others.
“Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic. With our chip, you can distribute a drug and then look for the effects on other tissues and measure the exposure and how it is metabolized,” said Linda Griffith, PhD, Professor of Teaching Innovation at MIT’s School of Engineering, and a senior author of the study, in the news release.
According to MIT, factors affecting the effectiveness of pharmaceuticals may include:
Genetics;
Environment;
Personal lifestyles; and,
Interactions with other drugs.
TechCrunch called the study “unprecedented,” pointing to the platform’s connection of so many tissues and the technology’s ability to keep them stable for weeks.
“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” Linda Griffith, PhD, MIT Professor, MIT School of Engineering, told Science Daily. “I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.” (Photo copyright: MacArthur Foundation.)
How “Body-on-a-Chip” Works
“Body-on-a-chip” is about the size of a tablet computer and links 10 organ types, including: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle.
Using microfluidic platform technology, the researchers placed one- to two-million cells from human tissue samples into the device and then pushed fluid through the chip to resemble blood flow, the Daily Mail reported, adding that MIT’s MPS platform design features:
Compartments made from a plastic block;
Passages for fluid to move (as a circulatory system does) between the compartments;
A water reservoir to limit fluid evaporation; and,
Ability to monitor flow of molecular exchanges and drug distribution.
Essentially, using the MIT device, a drug can be introduced to one organ, processed normally, and then passed to other organs for processing and use in other ways, TechCrunch summarized.
The physiome-on-a-chip system (above schematic) comprises bioengineered devices that nurture many interconnected 3D MPSs representing specified functional behaviors of each organ of interest, designed to capture essential features of in vivo physiology based on quantitative systems models tailored for individual applications such as drug fate or disease modeling. This technology could eventually be utilized for clinical laboratory and anatomic pathology testing. (Image and caption copyright: Victor O. Leshyk/Scientific Reports.)
Drug Delivery, Effects on Multiple Tissues Noted in MIT Study
The MIT researcher engineers reported these findings and accomplishments:
Delivering a drug to the gastrointestinal tissue;
Replicating digesting a drug;
Observing as a drug was transported to other tissues and metabolized;
Measuring a drug’s path; and,
Noting effects of a drug on different tissues and how drugs break down.
“The huge potential of MPS technology is revealed by connecting multiple organ chips in an integrated system for in vitropharmacology. This study beautifully illustrates that multi-MPS ‘physiome-on-a-chip’ approaches, which combine the genetic background of human cells with physiologically relevant tissue-to-media volumes, allow accurate prediction of drug pharmacokinetics and drug absorption, distribution, metabolism, and excretion,” said Kevin Healy, PhD, Professor of Bioengineering and Materials Science and Engineering, at University of California Berkeley in the MIT news release. Healy was not involved in the research.
Unique Device Design
In addition to making it possible to study so many different tissue types, the device design, according to MIT, is unique for these reasons:
Its open microfluidic system, rather than a closed system, means the lid can be removed to manipulate tissue samples;
Instead of external pumps common in closed systems, the MIT team used “on-board pumps” to control flow of liquid between the organs; and,
The pumps used enabled larger engineered tissues, such as those from tumors in an organ, to be assessed.
The MIT engineers next plan to focus on specific organs—including the brain, liver, and gastrointestinal tissue—to model Parkinson’s disease, Digital Trends reported.
As healthcare providers and medical laboratories adopt precision medicine, MIT’s contributions are both timely and important. The ability to accommodate many different configurations in one platform is impressive, and something Dark Daily has been anticipating.
Goal is to shift glucose testing away from medical laboratories and make it easier for diabetics to do their own testing, while capturing glucose test results in patient records
Because of the tremendous volume of glucose tests performed daily throughout the world, many companies are developing non-invasive methods for glucose testing. Their goal is a patient-friendly technology that does not require a needle stick or venipuncture and may even eliminate the need to send specimens to a medical laboratory.
What is intriguing about these initiatives is that, in their final form, they may create a flow of useful diagnostic data reported to clinical laboratories in real time. This would create the opportunity for pathologists and lab scientists to consult with the patients’ physicians, while archiving this test result data in the laboratory information system (LIS).
These glucose monitoring methods would also ensure that a complete longitudinal record of patient tests results is available to all the physicians practicing in an accountable care organization (ACO), medical home, or hospital. (more…)
