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.
Human microbiota is linked to many diseases but could hold the key for advanced clinical laboratory tests and targeted precision medicine therapies Study of the human microbiome continues to provide understanding and knowledge regarding gut bacteria and its many benefits, and incites development into new clinical laboratory tests. However, a new study reveals that our bodies might also put gut bacteria under stress leading to better health. Traditionally, scientists believe the human gut is a...
Microbiome is once again leading scientists toward a new understanding of how human gut bacteria can impact the efficacy and side-effects of certain cancer therapies
Anatomic pathology researchers already know that a person’s genetics can affect the results of cancer treatments. Now it is becoming clear that a patient’s microbiome—which includes gut bacteria—may also impact the efficacy of particular cancer treatments. A recent study showed that gut bacteria can be used to determine whether a cancer drug will work for a certain individual and also if the patient might suffer side effects from certain cancer treatments.
Working with this knowledge, diagnostic test companies may possibly develop new clinical laboratory tests designed to help physicians better diagnose and treat cancer patients. This, in turn, advances personalized medicine and treatments for chronic diseases tailored to patients’ specific physiologies and conditions. This is a healthcare trend where medical laboratories can expect to play a critical role.
Gut Bacteria as Important as Genetics in Cancer Treatments
Libusha Kelly, PhD, Assistant Professor in the Departments of Systems and Computational Biology, and Microbiology and Immunology, led researchers from the Albert Einstein College of Medicine located in Bronx, N.Y., in conducting the study.
“We’ve known for some time that people’s genetic makeup can affect how they respond to a medication,” noted Kelly in an Einstein news release. “Now, it’s becoming clear that variations in one’s gut microbiome—the population of bacteria and other microbes that live in the digestive tract—can also influence the effects of treatment.”
Irinotecan is administered intravenously to colorectal cancer patients in an inactive form and is metabolized to an active form by liver enzymes. The drug is later converted back to an inactive form by other liver enzymes and the addition of a Glucuronidase chemical group. The irinotecan then enters the intestine for expulsion by the body.
Taken from the Einstein College of Medicine published study, the graph above illustrates “Two distinct metabolizer phenotypes or ‘metabotypes’ based on % SN-38 formation during a time course incubation of SN-38G with fecal samples from 20 individuals quantified by LC-MS/MS. Participants were sub-grouped into low (n = 16) and high (n = 4) metabolizer phenotypes. All samples were run in triplicate and values are the mean ± sem.” (Graphic copyright: Nature/Albert Einstein College of Medicine.)
However, bacteria residing in the digestive tract of some individuals prevent the medication from metabolizing properly and reactivates the medication, which transforms the irinotecan into a toxic substance that can cause side effects.
To perform the research, Kelly and her team collected fecal samples from 20 healthy individuals and treated those samples with inactive irinotecan. The samples were then examined and categorized by whether or not they were able to metabolize or reactivate the drug.
Identifying Potential for Side Effects in Patients a Powerful Tool for Medical Laboratories
Irinotecan can cause severe diarrhea and dehydration in up to 40% of patients who take the medication. By focusing on the presence of beta-glucuronidase (enzymes that are used to catalyze the breakdown of complex carbohydrates) the researchers found that gut bacteria can also be used to distinguish which patients will encounter side effects from the drug.
“As you can imagine, such patients are already quite ill, so giving them a treatment that causes intestinal problems can be very dangerous,” said Kelly in the news release. “At the same time, irinotecan is an important weapon against this type of cancer.”
Four of the 20 subjects in the study were determined to be high metabolizers. Due to differences in the composition of their microbiomes, the team concluded that the high metabolizers were more likely to experience side effects from irinotecan.
The research also demonstrated that beta-glucuronidase enzymes in the gut may adversely interact with some commonplace drugs, such as ibuprofen and other nonsteroidal anti-inflammatory medications (NSAIDs), morphine, and Tamoxifen, a drug that is prescribed mainly to breast cancer patients.
“In these cases, the issue for patients may not be diarrhea,” states Kelly in the news release. “Instead, if gut bacteria reactivate those drugs, then patients might be exposed to higher-than-intended doses. Our study provides a broad framework for understanding such drug-microbiome interactions.”
Microbiome Takes Center Stage in Pathology Research
As Dark Daily previously reported, from extending life to developing more powerful treatments for chronic diseases, the human microbiome is quickly becoming an important subject of research studies. The findings from such studies will trigger advances in precision medicine. And, the clinical laboratory assays developed from this research will give physicians the knowledge needed to select the most appropriate drug therapies and treatments for individual patients.
