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Clinical Laboratories and Pathology Groups

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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

Orchid Health Announces Release of First Commercially-Available Whole Genome Sequencing Service for Certain Diseases in Preimplantation Embryos

Clinical laboratory managers should note that this company’s new diagnostic offering involving screening embryos for specific genetic conditions is not without controversy

Is the world ready for whole genome sequencing (WGS) of preimplantation embryos to help couples undergoing in vitro fertilization (IVF) treatments know if their embryos  have potential genetic health problems? Orchid Health, a clinical preimplantation genetic testing (PGT) laboratory that conducts genetic screening in San Francisco, believes the answer is yes! But the cost is high, and the process is not without controversy.

According to an article in Science, Orchid’s service—a sequencings of the whole human genome of preimplantation embryos at $2,500 per embryo tested—“will look not just for single-gene mutations that cause disorders such as cystic fibrosis, but also more extensively for medleys of common and rare gene variants known to predispose people to neurodevelopmental disorders, severe obesity, and certain psychiatric conditions such as schizophrenia.”

However, Science also noted that some genomics researchers “claim the company inappropriately uses their data to generate some of its risk estimates,” adding that the “Psychiatric Genomics Consortium (PGC), an international group of more than 800 researchers working to decode the genetic and molecular underpinnings of mental health conditions, says Orchid’s new test relies on data [PGC] produced over the past decade, and that the company has violated restrictions against the data’s use for embryo screening.”

There are some who assert that a whole genome sequence of an embryo—given today’s state of genetic technology and knowledge—could generate information that cannot be interpreted accurately in ways that help parents and doctors make informed prenatal testing decisions. At the same time, criticisms expressed by the PGC raise reasonable points.

Perhaps this is a sign of the times. Orchid Health is the latest genetic testing company that is looking to get ahead of genetic testing competitors with its diagnostics offerings. Meanwhile, knowledgeable and credible experts question the appropriateness of this testing, given the genetic knowledge that exists today.

Noor Siddiqui

“This is a major advance in the amount of information parents can have,” Orchid’s founder and CEO Noor Siddiqui (above) told CNBC. “The way that you can use that information is really up to you, but it gives a lot more control and confidence into a process that, for all of history, has just been totally left to chance.” Should Orchid Health’s analysis prove useful, pediatricians could order further clinical laboratory prenatal testing to confirm and diagnose potential genetic diseases for parents. (Photo copyright: General Assembly.)

Orchid Receives World-class Support

Regardless of the pushback from some genetic researchers, Orchid has attracted several world-class geneticists and genetics investors to its board of advisors. They include:

The WGS test, according to Orchid, detects genetic errors in embryos that are linked to severe illnesses before a pregnancy even begins. And by sequencing 99% of an embryo’s DNA, the test can spot potential health risks that could affect a future baby.

According to its website, the PGT lab company uses the WGS data to identify both monogenic (single-gene) and polygenic (multiple-gene) diseases, including:

The company also claims its genetic screening can predict the risk of brain health issues in the unborn, such as Alzheimer’s disease, bipolar disorder, and schizophrenia, as well as heart health issues such atrial fibrillation and coronary artery disease.

Other health problems such as celiac disease and Type I/II diabetes also can be forecasted with the test, Orchid claims. 

Not all Genetics Experts Agree

Orchid is not without its critics. Knowledgeable, credible experts have questioned the appropriateness of this type of genetic testing. They fear it could become a modern-day form of eugenics.

Andrew McQuillin, PhD, Professor of Molecular Psychiatry at University College London, has concerns about Orchid’s preimplantation genetic testing. He maintains that it is difficult to control how such data is used, and that even the most accurate sequencing techniques do not predict disease risk very well. 

“[Polygenic risk scores are] useful in the research context, but at the individual level, they’re not actually terribly useful to predict who’s going to develop schizophrenia or not,” McQuillin told Science. “We can come up with guidance on how these things should be used. The difficulty is that official guidance like that doesn’t feature anywhere in the marketing from these companies.”

McQuillin also stated that researchers must have an extensive discussion regarding the implications of this type of embryo screening.

“We need to take a look at whether this is really something we should be doing. It’s the type of thing that, if it becomes widespread, in 40 years’ time, we will ask, ‘What on Earth have we done?’” McQuillin emphasized.

Redefining Reproduction

It takes about three weeks for couples to receive their report back from Orchid after completing the whole genome sequence of a preimplantation embryo. A board-certified genetic counselor then consults with the parents to help them understand the results. 

Founder and CEO Noor Siddiqui hopes Orchid will be able to scale up its operations and introduce more automation to the testing process to the cost per embryo.

“We want to make this something that’s accessible to everyone,” she told CNBC.

“I think this has the potential to totally redefine reproduction,” she added. “I just think that’s really exciting to be able to make people more confident about one of the most important decisions of their life, and to give them a little bit more control.”

Clinical laboratories have long been involved in prenatal screening to gain insight into risk levels associated with certain genetic disorders. Even some of that testing comes with controversy and ambiguous findings. Whether Orchid Health’s PGT process delivers accurate, reliable diagnostic insights regarding preimplantation embryos remains to be seen.

—JP Schlingman

Related Information:

Genetics Group Slams Company for Using Its Data to Screen Embryos’ Genomes

Reproductive Startup Launches Test to Identify an Embryo’s Genetic Defects Before an IVF Pregnancy Begins

What Is the Difference Between Monogenic and Polygenic Diseases?

First Clinical Validation of Whole Genome Screening on Standard Trophectoderm Biopsies of Preimplantation Embryos

Orchid Tests Embryos for Genetic Diseases. It Just Raised $12 Million with This 11-Slide Pitch Deck

Whole-Genome Sequencing, Aided by Bioinformatics Analytical Software, Offers Quick, Accurate Test for Diagnosing Diseases Caused by Single-Gene Mutations

A new approach to genetic testing of critically ill children, developed by researchers at Children’s Mercy Hospital, can be a road map other medical laboratories can follow  

In Kansas City, a medical team at Children’s Mercy Hospital has demonstrated that rapid whole human genome sequencing, when combined with interpretative software, can return clinically actionable answers quickly enough to be of value to physicians who are diagnosing patients showing symptoms of genetic conditions.

As many pathologists and clinical laboratory managers know, childrens’ hospitals across the nation are often at the vanguard of using molecular diagnostics and genetic tests to guide diagnosis and treatment of pediatric patients. Having the capability to make fast and accurate diagnoses of genetic conditions gives physicians at these institutions the ability to significantly improve the outcomes of their patients.

A report published by Medpagetoday.com reported the findings of researchers at Children’s Mercy Hospital. (more…)

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