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European Researchers Discover Gut Bacteria That Can Help Create Universal O-Type Blood

Should further study validate these findings, clinical laboratories managing hospital blood banks would be among the first to benefit from an abundance of universal donor blood

In a surprising outcome for microbiome research, scientists at the Technical University of Denmark (DTU) and Sweden’s Lund University discovered that the bacteria Akkermansia muciniphila, which resides in the human gut, produces enzymes that can be used to process whole blood in ways that could help produce type-O blood. This “universal” blood type can be given to patients during transfusions when other blood types are in short supply.

Receiving the wrong type of blood via a transfusion could result in a fatal reaction where the immune system launches an attack on foreign antigens. As blood bankers and clinical laboratory scientists know, the A antigens in type A blood are not compatible with the B antigens in type B blood. Type-O blood completely lacks these antigens, which explains why it can be used for individuals of any blood type. 

The DTU/Lund discovery—still in its initial stages of development—could eventually give blood bankers in hospital laboratories a way to expand their supply of universal type-O blood. Although individuals with type-O blood are universal donors, often the available supply is inadequate to meet the demand.

“For the first time, the new enzyme cocktails not only remove the well-described A and B antigens, but also extended variants previously not recognized as problematic for transfusion safety,” said Maher Abou Hachem, PhD, Professor of Biotechnology and Biomedicine at DTU, one of the authors of the study, in a news release.

Discovering a way that ensures any blood type can donate blood for all blood types could increase the supply of donor blood while reducing the costs and logistics affiliated with storing four separate blood types. Additionally, the production of a universal blood type using gut microorganisms could reduce the waste associated with blood products nearing their expiration dates. 

Whole blood must be used within 42 days after being collected. Having more units of the universal donor blood type would be extremely beneficial in how blood banks manage their blood supply and may revolutionize transfusions. The scientists published their findings in the journal Nature Microbiology titled, “Akkermansia Muciniphila Exoglycosidases Target Extended Blood Group Antigens to Generate ABO-Universal Blood.”

“We are close to being able to produce universal blood from group B donors, while there is still work to be done to convert the more complex group A blood,” said Maher Abou Hachem, PhD (above), Professor of Biotechnology and Biomedicine at DTU in a news release. “Our focus is now to investigate in detail if there are additional obstacles and how we can improve our enzymes to reach the ultimate goal of universal blood production,” he added. Hospital clinical laboratories that manage blood banks will be among the first to benefit from this new process once it is developed and cleared for use in patient care. (Photo copyright: Technical University of Denmark.)

Creating Universal Donor Blood

The bacterium Akkermansia muciniphila is abundant in the guts of healthy humans. It produces valuable compounds, and it is able to break down mucus in the gut and can have significant, positive effects on body weight and metabolic markers.

“What is special about the mucosa is that bacteria, which are able to live on this material, often have tailor-made enzymes to break down mucosal sugar structures, which include blood group ABO antigens. This hypothesis turned out to be correct,” Hachem noted in the DTU news release.

“Instead of doing the work ourselves and synthesizing artificial enzymes, we’ve asked the question: What looks like a red [blood] cell surface? The mucus in our gut does. So, we simply borrowed the enzymes from the bacteria that normally metabolize mucus and then applied them to the red [blood] cells,” Martin Olsson MD, PhD, professor of hematology and transfusion medicine at Lund University, told Live Science. “If you think about it, it’s quite beautiful.”

The researchers successfully identified long strings of sugar structures known as antigens that render one blood type incompatible with another. These antigens define the four blood types: A, B, AB and O. They then used a solution of gut bacteria enzymes to remove the sugar molecules present on the surface of red blood cells (RBCs).

“We biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions,” the study authors wrote in Nature Microbiology. “Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analysis of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module.”

“Universal blood will create a more efficient utilization of donor blood, and also avoid giving ABO-mismatched transfusions by mistake, which can otherwise lead to potentially fatal consequences in the recipient. When we can create ABO-universal donor blood, we will simplify the logistics of transporting and administering safe blood products, while at the same time minimizing blood waste,” Olsson said in the news release.

Future Progress

The researchers have applied for a patent for the enzymes and their method of enzyme treatment. The two educational institutions hope to make further progress on this joint project over the next three years. They eventually hope to test their theory in controlled patient trials and make it available for commercial production and clinical use.

More research and clinical studies are needed to prove the effectiveness of this discovery. Clinical laboratory professionals—particularly those who manage hospital blood banks—will want to follow DTU’s research. It could someday lead to the availability of a more abundant supply of universal donor blood for transfusions.

—JP Schlingman

Related Information:

Akkermansia Muciniphila Exoglycosidases Target Extended Blood Group Antigens to Generate ABO-universal Blood

Enzymes Open New Path to Universal Donor Blood

Gut Bacteria Can Help Create Artificial Group O Blood

Lab-made Universal Blood Could Revolutionize Transfusions. Scientists Just Got One Step Closer to Making It

Universal Donor Blood Significantly Closer Thanks to Enzymes Found in Gut Bacteria

A Gut Bacteria Could Hold the Key to Universal Blood, Revolutionizing Transfusion Medicine

How Gut Enzymes Could Make Universal Donor Blood Possible

Linköping University/University of Florida Study Finds Gut Bacteria May Affect Developing Neurodevelopmental Disorders in Infants

Further research could eventually lead to clinical laboratory biomarkers and screening tests to identify infants whose gut bacteria may predispose them to neurodevelopment disorders later in life

Microbiologists and clinical laboratory scientists working with gut bacteria will be intrigued to learn that a study conducted by scientists from Linköping University in Sweden and the Department of Microbiology and Cell Science at the University of Florida (UFL) recently found that gut microbiota (aka, gut flora) in infancy can be correlated with developing a neurodevelopmental disorder (ND) later in life.

The researchers analyzed patient records from the 20-year All Babies in Southeast Sweden (ABIS) prospective cohort study into the etiology of obesity, diabetes, and other diseases. They found that “disturbances” in the microbiomes of children during the first years of life could be linked to later ND diagnoses, according to Neuroscience News.

Such ND diagnoses include autism spectrum disorder (autism), Attention Deficit Hyperactivity Disorder (ADHD), communication disorders, and intellectual disability.

“We’ve found associations with some factors that affect gut bacteria, such as antibiotic treatment during the child’s first year, which is linked to an increased risk of these diseases,” stated pediatrician Johnny Ludvigsson, MD, PhD, Senior Professor, Department of Biomedical and Clinical Sciences at Linköping University, who co-led the study, in a Linköping University news release.

“Analyzing over 16,000 children from the ABIS study, researchers identified significant biomarkers in cord blood and stool samples that correlate with future diagnoses of these disorders,” Neuroscience News reported.

This study adds evidence to the growing theory that every individual’s microbiome has much to do with his/her state of health and specific health conditions.

The scientists published their findings in the journal Cell titled, “Infant Microbes and Metabolites Point to Childhood Neurodevelopmental Disorders.”

“We can see in the study that there are clear differences in the intestinal flora already during the first year of life between those who develop autism or ADHD and those who don’t,” said pediatrician and study co-author Johnny Ludvigsson, MD, PhD (above), Senior Professor, Department of Biomedical and Clinical Sciences at Linköping University, in a news release. Clinical laboratory scientists and microbiologists who work with gut microbiota will find these observations intriguing. (Photo copyright: Linköping University.)

Analysis of the ABIS Study

To conduct their study, the researchers analyzed the health records of 16,440 children born between 1997 and 1999 who participated in the ABIS study. The subjects were a close representation of the general Swedish population and were followed from birth into their twenties. 

Research showed that 1,197 of the 16,440 children (7.28%) had been diagnosed with either autism, ADHD, communication disorders, or an intellectual disability. 

The researchers also surveyed the ABIS study participants concerning their lifestyles and environmental factors during childhood. They analyzed substances found in the umbilical cord blood and stool bacteria collected at age one in some of the study participants. Cord blood remains in the placenta and umbilical cord after birth and is rich in stem cells

“The remarkable aspect of the work is that these biomarkers are found at birth in cord blood or in the child’s stool at one year of age over a decade prior to the diagnosis,” said Eric Triplett, PhD, Professor and Chair of the Department of Microbiology and Cell Science at UFL and a co-leader of the study, in the Linköping University news release.

The investigation found that children who had numerous ear infections during the first year of life were more prone to receiving a diagnosis of a neurodevelopmental disorder later in life. The scientists surmised that it was not the infections that caused the issues. Rather, it was that repeated antibiotic treatments had disturbed the balance of healthy gut bacteria.

“We’re not trying to say that antibiotics are necessarily a bad thing,” stated Angelica Ahrens, PhD, Assistant Research Scientist in the Triplett Research Group at the University of Florida and first author of the study, in a UFL blog. “But perhaps overuse can be detrimental to the microbiome, and for some children, for whatever reason, their microbiome might not recover as readily.”

Deficits in Important Bacteria

The researchers discovered that the presence of Citrobacter bacteria increased the risk of a future ND diagnosis. According to ScienceDirect, “organisms of the genus Citrobacter are gram-negative bacilli that are occasional inhabitants of the gastrointestinal tract and are responsible for disease in neonates [newborns that are four weeks or younger] and debilitated or immunocompromised patients.”

They also discovered that the absence of Coprococcus bacteria increased the risk of getting an ND as well. One of the main producers of butyrate, Coprococcus is known to support gut barrier function, suppress harmful bacteria, and contain anti-inflammatory properties.

Coprococcus and Akkermansia muciniphila have potential protective effects,” said Ahrens in the Linköping University news release. “These bacteria were correlated with important substances in the stool, such as vitamin B and precursors to neurotransmitters which play vital roles orchestrating signaling in the brain. Overall, we saw deficits in these bacteria in children who later received a developmental neurological diagnosis.”

Environmental/Behavioral Findings of the ABIS Study

Through the analysis of toxins present in study participants’ cord blood, the researchers confirmed that risk of developing an ND increases when babies are exposed to parents who smoke. The scientists also found that breastfeeding offers a protective effect against NDs.

More research is needed to determine whether gut flora in infants can have an effect on developing NDs later in life, and it is not yet known if similar findings will be detected in other populations. Nevertheless, the findings that many biomarkers for NDs can be observed in infancy may enable scientists to create clinical laboratory screening protocols, preventative measures, and innovative treatments for neurodevelopmental disorders. 

Further research and studies linking certain microbiome factors to specific health conditions will create opportunities for microbiologists and clinical laboratories as well, to perform diagnostic testing that identifies if a patient—in this case a newborn or infant—has a microbiome that will lead to immediate or later neurological health conditions.   

—JP Schlingman

Related Information:

Autism and ADHD Are Linked to Disturbed Gut Flora Very Early in Life

Early Gut Flora Imbalance May Predict Autism and ADHD

Disturbed Gut Flora in Early Years Linked to Autism

Infant Microbes and Metabolites Point to Childhood Neurodevelopmental Disorders

All Babies in Southeast Sweden (ABIS) – ABIS-II. A Prospective Cohort Study of the Aetiology of Obesity, Diabetes and Other Diseases.

UF and Swedish Researchers Connect Childhood Microbiome with Development of Autism, ADHD

University of Ghent Belgium Research Team Finds Stool Transplants Improve Motor Symptoms in Early-stage Parkinson’s Disease Patients

Findings could lead to clinical laboratory tests that help physicians identify microbes lacking in the microbiomes of their Parkinson patients

Microbiologists and clinical laboratory scientists know that gut microbiome can be involved in the development of Parkinson’s disease, a progressive neurological disorder that affects the nervous system due to damage caused to nerve cells in the brain. There is no cure for the illness. But a new treatment developed by researchers at the VIB Center for Inflammation Research at the University of Ghent in Belgium, may help to alleviate the symptoms.

During a clinical trial, VIB Center for Inflammation Research (VIB-IRC) scientists discovered that fecal microbiota transplantation (FMT), also known as a stool transplant, can improve motor skills in some Parkinson’s patients, according to Neuroscience News.

Parkinson’s disease (PD) develops when a protein called alpha-synuclein misfolds and forms into bundled clusters damaging nerve cells in the brain that produce dopamine. These formations, which are believed to appear in the gastrointestinal wall in the early stages of PD, then reach the brain via the vagus nerve leading to typical PD symptoms in patients.

Dopaminergic medication, deep brain stimulation, and speech and occupational therapy are some of the treatments currently available to people with Parkinson’s disease, but researchers are constantly on the lookout for more and better treatments,” Medical News Today reported.

The scientists published their findings in eClinicalMedicine titled, “Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Mild to Moderate Parkinson’s Disease (GUT-PARFECT): A Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial.”

“Our study provides promising hints that FMT can be a valuable new treatment for Parkinson’s disease,” Roosmarijn Vandenbroucke, PhD (above), Principal Investigator, VIB-UGent Center for Inflammation Research and full professor, UGent Department of Biomedical molecular biology, Faculty of Sciences, told Neuroscience News. “More research is needed, but it offers a potentially safe, effective, and cost-effective way to improve symptoms and quality of life for millions of people with Parkinson’s disease worldwide.” Clinical laboratories will likely be involved in identifying the best microbes for the FMT treatments. (Photo copyright: University of Ghent.)

Correlation between Gut Microbiome and Neurogenerative Disease

To perform their clinical study—referred to as GUT-PARFECT—the IRC researchers first recruited patients with early-stage PD and healthy donors who provided stool samples to the Ghent Stool Bank. The PD patients received the healthy stool via a tube inserted into the nose which led directly into the small intestine.

The FMT procedures were performed on 46 patients with PD between December 2020 and December 2021. The participants in this group ranged in ages from 50 to 65. There were 24 PD patients in the placebo group, and a total of 22 donors provided the healthy stool. Clinical evaluations were performed at baseline, three, six, and 12 months.

After 12 months, the group that received the transplants showed a reduction in symptoms compared to the placebo group. Their motor score on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) improved by a mean of 5.8 points. The improvement registered on the same scale for the placebo group was 2.7 points.

Developed in the 1980s, the MDS-UPDRS is a scale utilized to evaluate various aspects of PD by measuring patient responses via a questionnaire rating several issues (such as cognitive impairment, apathy, depression, and anxiousness) common in PD patients from normal to severe. It is divided into four parts:

  • Part I: Non-motor experiences of daily living.
  • Part II: Motor experiences of daily living.
  • Part III: Motor examination.
  • Part IV: Motor complications.

During the final six months of the research, the improvement in motor symptoms became even greater. To the VIB-IRC researchers this implied that an FMT may have long-lasting effects on PD patients. The FMT study group also experienced less constipation, a condition that can be bothersome for some PD patients.

“Our results are really encouraging!” said the study’s first author, Arnout Bruggeman, MD, PhD student, VIB-UGent Center for Inflammation Research, in a UGent News release. “After twelve months, participants who received the healthy donor stool transplant showed a significant improvement in their motor score, the most important measure for Parkinson’s symptoms.”

Findings Could Lead to Other Targeted Therapies for PD

The VIB-IRC researchers believe there is a correlation between the gut microbiome and Parkinson’s disease.

“Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages,” the IRC researchers wrote in eClinicalMedicine.  

“Our next step is to obtain funding to determine which bacteria have a positive influence. This could lead to the development of a ‘bacterial pill’ or other targeted therapy that could replace FMT in the future,” Debby Laukens, PhD, Associate Professor, Ghent University, told Neuroscience News.

According to the Parkinson’s Foundation website, nearly one million people in the US live with PD. It is second only to Alzheimer’s disease in the category of neurodegenerative diseases.

More research and studies are needed before the VIB-IRC’s stool transplant treatment can be used in clinical care. As researchers learn more about which specific strains of bacteria are doing the beneficial work in PD patients, that data could eventually lead to clinical laboratory tests performed to help physicians identify which microbes are lacking in the microbiomes of their PD patients, and if fecal transplants could help those patients.

—JP Schlingman

Related Information:

Fecal Bacteria Transplant May Improve Parkinson’s Symptoms

Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Mild to Moderate Parkinson’s Disease (GUT-PARFECT): A Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial

Stool Transplantation Shows Promise For Parkinson’s Disease

Fecal Microbiota Transplant Eases Parkinson’s Symptoms in Trial

Stool Transplant Could Improve Motor Symptoms in Parkinson’s Disease

In Conversation: Why Parkinson’s Research is Zooming in on the Gut

At the University of Michigan, Research Study Indicates how Composition of Gut Microbiome May Serve as Complementary, Noninvasive Screening Tool for Colon Cancer

If validated by additional research, microbiologists, pathologists, and medical laboratory professionals might soon find analysis of the human microbiome to be a useful marker in screening for colon cancer

Microbiologists may play a greater role in the early detection of colorectal cancer, if the findings of a research study at the University of Michigan (UMich) are confirmed with additional clinical studies.

Combining gut microbiome analysis with traditional risk factors for colorectal cancer—such as body mass index (BMI), age, and race—significantly improved the ability of pathologists to distinguish healthy people from those with precancerous or cancerous lesions, wrote researchers from the UMich in a scholarly paper published in the November 2014 issue in Cancer Prevention Research.

Research findings indicate that gut microbiomes may be a major factor in development of colorectal cancer. However, more research is required to determine if this microbial community has the potential to be clinically useful as screening tool for early-stage disease. (more…)

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