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.
Technology enables sampling of an individual’s microbiome over time to observe changes associated with different illnesses or different diets
There is now a pill-sized device that can non-invasively collect and deliver a sample of gut bacteria taken directly from specific areas of a person’s gastrointestinal (GI) tract. One benefit of this new technology is that it can collect samples from the upper digestive system. Although not ready for clinical use, this is the kind of technology that would enable microbiologists and clinical laboratory scientists to add more microbiome assays to their test menu.
Researchers at Stanford University, Envivo Bio, and the University of California, Davis (UC Davis) have developed a vitamin capsule-sized device—dubbed CapScan—that can measure the microbial, viral, and bile acid profiles contained in the human intestines as it passes through on its way to being expelled.
Currently, scientists rely on stool samples to collect similar data as they are easy to gather and readily available. However, stool samples may not provide the most accurate analysis of the various microorganisms that reside in the human gut.
“Measuring gut metabolites in stool is like studying an elephant by examining its tail,” said Dari Shalon, PhD, Founder and CEO at Envivo Bio, one of the authors of the study, in a UC Davis news release. “Most metabolites are made, transformed, and utilized higher up in the intestines and don’t even make it into the stool. CapScan gives us a fuller picture of the gut metabolome and its interactions with the gut microbiome for the first time.” Shalon is the inventor of the CapScan device.
This demonstrates how technological advancements are giving scientists new diagnostic tools to guide selection of therapies and to monitor a patient’s progress.
Microbiologists will take a special interest in this published study because, once confirmed by further studies, it would provide microbiology laboratories and clinical labs with a new way to collect samples. In clinical laboratories throughout the country, handling fecal specimens is considered an unpleasant task. Once cleared for clinical use, devices like CapScan would be welcomed because the actual specimen would be contained within the capsule, making it a cleaner, less smelly specimen to handle than conventional fecal samples.
“This capsule and reports are the first of their kind,” said Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis, in a news release. “All other studies on human gut microbiota focused on stool as a surrogate for colon metabolism. However, of course, the fact is that 90% of human digestion happens in the upper intestine, not the colon.” Clinical laboratories have long worked with stool samples to perform certain tests. If CapScan proves clinically viable, labs may soon have a new diagnostic tool. (Photo copyright: UC Davis.)
Collecting Small Intestine Microbiota
Human digestion occurs mostly in the small intestine where enzymes break down food particles so they can later be absorbed through the gut wall and processed in the body. Stool samples, however, only sample the lower colon and not the small intestine. This leaves out vital information about a patient.
“The small intestine has so far only been accessible in sedated people who have fasted, and that’s not very helpful,” Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis and one of the study authors, said in the news release.
According to their Nature paper, to perform their research the team recruited 15 healthy adults to participate in the study. Each participant swallowed four CapScan “pills,” either twice daily or on two consecutive days. The pills were designed to respond to different pH (potential of hydrogen) levels.
Each pill’s pH-sensitive outer coating enables scientists to select which area of the intestinal tract to sample. The outer coating dissolves at a certain point as it travels from the upper intestine to the colon. When this happens, a one-way valve gathers miniscule amounts of biofluids into a tiny, inflatable bladder. Once full, the bladder seals shut and the CapScan continues its journey until it is recovered in the stool. The researchers then genetically sequenced the RNA from the collected samples.
The scientists discovered that the microbiome varied substantially at distinctive sections of the GI tract. When compared to collected stool samples, the researchers determined that traditional stool sampling could not capture that variability.
“There’s enormous potential as you think about how the environment is changing as you go down the intestinal tract,” Kerwyn Huang, PhD, Professor of Bioengineering and of Microbiology and Immunology at Stanford, one of the authors of the study, told Drug Discovery News. “Identifying how something like diet or disease affects the variation in the individual microbiome may even provide the potential to start discovering these important health associations.”
The genetic sequencing also revealed which participants had taken antibiotics within one to five months before the study because their data was so incongruous with the other participants. Those individuals had distinctive differences in their microbiome and bile acid composition, which illustrates that antibiotics can potentially affect gut bacteria even months after being taken.
Researchers Use Multiple ‘Omics’ Approach
The researchers used “multiomics” to analyze the samples. They identified the presence of 2,000 metabolites and found associations between metabolites and diet.
According to the Envivo Bio website, the CapScan allows for the regional measurement of:
“Overall, this device can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease,” Fiehn said in the press release.
Future of Collecting Gut Bacteria
Using CapScan is a non-invasive procedure that makes it possible to sample an individual’s microbiome once, or to monitor it over time to observe changes associated with different illnesses or diets. Since it takes time for the device to pass through the digestive system, it is not a rapid test, but initial studies show it could be more accurate than traditional clinical laboratory testing.
“This technology makes it natural to think about sampling from many places and many times from one person, and it makes that straightforward and inexpensive,” Huang said.
Advancements in technology continue to provide microbiology and clinical laboratories with new, innovative tools for diagnosing and monitoring diseases, as well as guiding therapy selection by medical professionals. Though more research and clinical studies are needed before a device like the CapScan can be commonly used by medical professionals, it may someday provide a cutting-edge method for collecting microbiome samples.
Research could lead to new microbiome assays that clinical laboratories could use to identify genetic and other health conditions in developing baby
It would seem to be common sense, but now a study conducted by the Broad Institute of MIT and Harvard confirms that a pregnant mother’s microbiome has an effect on the development of her baby’s own gut microbiota. These findings could create opportunities for clinical laboratories to help in diagnosing a broader range of health conditions by testing the gut bacteria of pregnant mothers.
The Broad Institute’s study suggests the mother’s gut microbiome helps form the baby’s gut bacteria not only during pregnancy and birth, but into the baby’s first year of life as well.
“This study helps us better understand how the rich community of microbes in the gut initially forms and how it develops during infancy,” said Tommi Vatanen, PhD, a co-first author on the study who is now a researcher and associate professor at the University of Helsinki, in a Broad Institute news release. “The microbiome is very dynamic and develops along with other systems, so there’s a lot going on in the first years of life.”
“We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said gastroenterologist and senior study author Ramnik Xavier, MD, of the Broad Institute. Clinical laboratories and microbiologists may soon have new tools for testing a mother’s microbiome during pregnancy. (Photo copyright: Maria Nemchuk, Broad Institute.)
Study Highlights Physiological Connection Between Mother and Child
This study, according to the Broad Institute news release, is the “first to uncover large-scale horizontal gene transfer events between different species of maternal and infant gut bacteria.” The researchers also found that the bacteria in the mother’s microbiome “donate” genes that go into the bacteria of her unborn child. The mother’s genes help the baby in other ways as well during pregnancy and after birth.
“Benign bacteria in the maternal gut share genes with the child’s intestinal microbes during early life, potentially contributing to immune and cognitive development,” states the news release, adding, “The microbiomes of the mother and baby change during pregnancy and the first year of life … some bacteria in the mother’s gut donate hundreds of genes to bacteria in the baby’s gut. These genes are involved in the development of the immune and cognitive systems and help the baby to digest a changing diet as it grows.”
The study also sheds light on a baby’s unique metabolites (chemicals produced by bacteria) and how they connect with the mother’s microbiome.
“This is the first study to describe the transfer of mobile genetic elements between maternal and infant microbiomes,” gastroenterologist Ramnik Xavier, MD, Core Institute Member, Director of the Immunology Program, and Co-Director of the Infectious Disease and Microbiome Program at the Broad Institute, told Neuroscience News.
“Our study also, for the first time, integrated gut microbiome and metabolomics profiles from both mothers and infants and discovered links between gut metabolites, bacteria, and breastmilk substrates,” he added.
Researchers Use Multiomics
The human microbiome influences health in many ways. For several years, Broad Institute scientists have been trying to better understand the human microbiome and the role it plays in diseases like type 1 diabetes, cancer, and inflammatory bowel disease.
According to the organization’s website, the scientists recently began using multiomics techniques in their research that include:
Xavier and his colleagues were particularly interested in the development of the microbiome during the first year of the baby’s life.
“The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites,” the researchers wrote in Cell. “Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to one year of age using longitudinal multiomics data.”
The researchers deployed bacterial DNA sequencing from stool samples of 70 mother and child pairs.
They found “hundreds of genes” in the infant gut bacterial genome that originated in the mother. According to the scientists, this suggests a mother does not transfer her genes all at once during childbirth. Instead, it likely occurs in an “ongoing” gene transfer from mother to baby through the baby’s first year of life, the news release explains.
Here are details on the study findings, according to Neuroscience News:
Genes associated with diet were involved in the “mother-to-infant interspecies transfer of mobile genetic elements.”
Infant gut metabolomes were less diverse than maternal metabolomes.
Infants had 2,500 unique metabolites not detected in the mothers.
Infants that received baby formula had distinct metabolites and cytokine signatures as compared to those receiving breast milk.
A link between pregnancy and an increase in steroid compounds could be due to impaired glucose tolerance in mothers.
“We also found evidence that prophages—dormant bacteriophages (viruses that reside on bacterial genomes)—contribute to the exchange of mobile genetic elements between maternal and infant microbiomes,” Xavier told Neuroscience News.
Research Could Lead to New Clinical Laboratory Assays
Microbiologists and clinical laboratory scientists are gaining a deeper understanding of the role gut bacteria play in many aspects of human life. But how a mother’s microbiome influences a baby’s development during and after birth is particularly intriguing.
“We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said Xavier in the Broad Institute news release. “This may be yet another benefit of prolonged bonding between mother and child, providing more chances for these beneficial gene transfer events to occur.”
Pediatricians, microbiologists, and clinical laboratories may one day have new microbiome assays to help identify a broad range of health conditions in mothers and infants and explore gut bacteria’s effects on a baby’s developing health.
If this technology proves viable on large scale, medical laboratories in hospitals that manage blood banks could have larger supplies of universal blood units
Once again, the amazing human microbiome is
at the heart of a new scientific breakthrough that could offer new tools for clinical
laboratories and provide much needed resources to emergency departments and
hospitals.
Canadian researchers at the University
of British Columbia (UBC) in Vancouver have discovered a microbe in the human gut
they believe is capable of converting donor blood into “universal” type-O blood.
“We have been particularly interested in enzymes that allow
us to remove the A or B antigens from red blood cells. If you can remove those
antigens, which are just simple sugars, then you can convert A or B to O blood,”
Stephen
Withers, PhD, a professor and biochemist at UBC explained in an American
Chemical Society (ACS) news release.
Such a breakthrough would be game-changing not only for
emergency departments that rely on much-needed supplies of universal-donor
blood, but also for the medical
laboratories that run most hospital blood banks.
Uncovering a method to transform type A blood into type O
would greatly enlarge the current blood supply because type-O blood can be
donated to patients regardless of which of the four main blood groups they
belong to—O, A, B, or AB.
This is yet another addition to a growing list of
discoveries involving human gut bacteria that Dark Daily has reported on in past years.
UBC scientists relied on metagenomics—a technique
that enables researchers to study microbial communities using DNA sequencing—to investigate
enzymes that potentially could destroy all the A and B antigens from red blood cells,
thereby converting type A and B blood into Type O universal blood.
“With metagenomics, you take all of the organisms from an
environment and extract the sum total DNA of those organisms all mixed up
together,” Withers said in the ACS news release.
Withers’ team considered sampling DNA from mosquitoes and
leaches but ultimately turned to the human body, where they found successful
candidate enzymes in the gut
microbiota. They focused on glycosylated proteins
called mucins that line the
gut wall, providing sugars that serve as attachment points for gut bacteria,
while also feeding them as they aid in digestion, the ACS report noted.
“By honing in on the bacteria feeding on those sugars, we
isolated the enzymes the bacteria use to pluck off the sugar molecules,”
Withers said in a UBC
statement. “We then produced quantities of those enzymes through cloning
and found that they were capable of performing a similar action on blood
antigens.”
Although enzymes long have been considered a key to transforming
donated blood to a common type, the gut enzymes the UBC team identified are 30
times more efficient at removing red blood cell antigens than previously
studied enzymes, the ACS news release noted. Their findings demonstrate once
again how the human microbiome is intertwined with many processes happening
within the body, opening the possibility of future novel uses of enzymes.
“Researchers have been studying the use of enzymes to modify blood as far back as 1982. However, these new enzymes can do the job 30 times better,” Stephen Withers, PhD (above), Professor and biochemist at the University of British Columbia, noted in the UBC statement. Should his technique for converting A and B blood types to type O prove successful on a large scale, emergency departments and medical laboratories that manage blood banks could finally gain a dependable source of blood. (Photo copyright: University of British Columbia.)
Zuri
Sullivan, an immunologist and PhD candidate at Yale University, believes the blood-converting
enzymes discovered by the USB team may be the first of many discoveries
revealed as researchers investigate the untapped potential of the gut
microbiome to solve medical challenges.
“The premise here is really powerful. There’s an untapped
genetic resource in the [genes] encoded by the gut microbiome,” she told Smithsonian Magazine.
Researchers Have High
Hopes but More Testing Is Needed
According to the UBC statement, Withers and UBC colleagues microbiologist
Steven Hallam,
PhD, and pathologist Jay
Kizhakkedathu, PhD, of the UBC Center for
Blood Research, are applying for a patent on the new enzymes, while working
to validate the enzymes and test them on a larger scale in preparation for
clinical testing.
In addition, the ACS news release notes that the UBC team “plans
to carry out directed
evolution, a protein engineering technique that simulates natural
evolution, with the goal of creating the most efficient sugar-removing enzyme.”
“I am optimistic that we have a very interesting candidate
to adjust donated blood to a common type,” Withers said in the ACS statement.
“Of course, it will have to go through lots of clinical trials to make sure
that it doesn’t have any adverse consequences, but it is looking very
promising.”
Fortune health journalist Sy Mukherjee praised the
UBC discovery, but warned against “coming to any overhyped conclusions” until
more testing is done.
“But if it’s a sustainable technique, the implications are
multifold,” he noted. “Especially given the nature of the technique itself,
which involves lopping off certain antigens (which are, in essence, simple
sugars) from particular red blood cells. The question is whether it can be used
on a wide-scale in a safe and efficient manner to create larger blood supplies
in times of need.”
That certainly is the question. For decades, scientists have
searched for the secret to creating universal blood and now it appears the
answer may have been lurking inside our bodies all along. Clinical laboratories
may soon see human microbiome become linked to even more discoveries that lead
to new tests and diagnostic tools.
Clinical laboratories could soon have new tests for determining how fast a patient’s digestive system is aging as part of a precision medicine treatment protocol
When it comes to assessing human age and longevity, much research has focused on telomeres in recent years. Now clinical laboratory managers and pathologists will be interested to learn that provocative new research demonstrates that the human microbiome may also contain useful information about aging. Microbes that can be diagnostic biomarkers may be one result of this research.
From preventing weight loss to improving cancer treatments to stopping aging, human microbiome—especially gut bacteria—are at the heart of many near miraculous discoveries that have greatly impacted clinical pathology and diagnostics development. Dark Daily has reported on so many recent studies and new diagnostic tools involving human gut bacteria it’s a wonder there’s anything left to be discovered. Apparently, however, there is!
Using artificial intelligence (AI) and deep-learning algorithms, researchers at Insilico Medicine in Rockville, Md., have developed a method involving gut bacteria that they say can predict the age of most people to within a few years. Located at Johns Hopkins University, Insilico develops “artificial intelligence for drug discovery, biomarker development, and aging research” notes the company’s website.
According to a paper published on bioRxiv, an online biomedical publications archive operated by Cold Spring Harbor Laboratory, the Insilico scientists have “developed a method of predicting [the] biological age of the host based on the microbiological profiles of gut microbiota” as well an “approach [that] has allowed us to define two lists of 95 intestinal biomarkers of human aging.”
“This microbiome aging clock could be used as a baseline to test how fast or slow a person’s gut is aging and whether things like alcohol, antibiotics, probiotics, or diet have any effect on longevity,” Alex Zhavoronkov, PhD (above), one of the study’s authors and founder of Insilico Medicine, told Science. (Photo copyright: Insilico Medicine.)
Clinical Laboratories
Might Be Able to Use AI and Gut Bacteria to Predict Age
To perform the study, the researchers collected 3,663 gut bacteria samples from 10 publicly available data sets containing age metadata and then analyzed the samples using a machine learning algorithm. The samples originated from 1,165 healthy individuals who were between the ages of 20 and 90. The individuals used for the study were from Austria, China, Denmark, France, Germany, Kazakhstan, Spain, Sweden, and the US.
The researchers divided the samples equally among three age
groups:
20 to 39 years old (young);
40 to 59 years old (middle aged); and,
60 to 90 years old (old).
The samples were then randomly separated into training and
validation sets with 90% of the samples being used for training and the
remaining 10% making up the validation set.
The scientists trained a deep neural network regressor to predict the age of the sample donors by looking at 95 different species of bacteria in the microbiome of the 90% training set. The algorithm was then asked to predict the ages of the remaining 10% of the donors by looking only at their gut bacteria.
They discovered that their computer program could accurately
predict an individual’s age within four years based on their microbiome. They also
were able to determine that 39 of the 95 species of bacteria examined were most
beneficial in predicting a person’s age.
In addition, the researchers found that certain bacteria in
the gut increase with age, while other bacteria decrease as people age. For
example, the bacterium Eubacterium
hallii, which is associated with metabolism in the intestines, was found to
increase with age. On the other hand, one of the most plentiful micro-organisms
in the gut, Bacteroides
vulgatus, which has been linked to ulcerative colitis,
decreases with age.
Understanding
Microbiome’s Link to Disease
The human microbiome consists of trillions of cells
including bacteria, viruses, and fungi, and its composition varies from
individual to individual. Scientific research, like that being conducted at
Insilico Medicine, expands our understanding of how gut bacteria affects human
health and how diseases such as inflammatory bowel disease, arthritis, autism, and obesity, are linked to the
microbiome.
This type of research could be used to determine how the
microbiomes of people living with certain illnesses deviate from the norm, and
possibly reveal unique and personalized ways to create healthier gut bacteria.
It also could help researchers and physicians determine the best interventions,
drugs, and treatments for individual patients dealing with diseases related to
aging. Such advancements would be a boon to precision medicine.
“Age is such an important parameter in all kinds of diseases.
Every second we change,” Zhavoronkov told Science. “You
don’t need to wait until people die to conduct longevity experiments.”
Further research is needed to develop these findings into
diagnostic tests acceptable for use in patient care. However, such tests could
provide microbiologists and clinical laboratories with innovative tools and
opportunities to help physicians diagnose patients and make optimal treatment
decisions.
