Microbiologists and clinical laboratory professionals should play a key role in the ordering and use of microbiome testing
International experts in the field of microbiome testing recently published a consensus document that establishes guidelines for the use and distribution of microbiota diagnostics they claim are long overdue. Companies offering direct-to-consumer (DTC) microbiome test kits continue to increase in number and popularity. But some experts in the human microbiome field—including microbiologists and clinical laboratory professionals—remain apprehensive regarding the science behind this type of home testing.
A Gemelli University news release states, “The intestinal microbiota could perhaps one day become a routine tool for the early diagnosis of many diseases and treatment guidance, but at the moment there is a lack of solid scientific evidence to support these indications. Yet, day by day, the offers of commercial kits are multiplying to carry out do-it-yourself tests, at the moment completely devoid of scientific significance and solidity.”
It continues, “To put a stop to this drift, a panel of international experts, coordinated by Dr. Gianluca Ianiro, has drafted the ‘instructions for use’ for best practices related to microbiota testing and recommendations for its indications, analysis methods, presentation of results and potential clinical applications.”
“This document marks a decisive step towards a standardization that has become indispensable making the microbiota an increasingly integrated element in personalized medicine,” said gastroenterologist Antonio Gasbarrini, MD (above), dean of the faculty of medicine and surgery and full professor of internal medicine at Catholic University of the Sacred Heart. “In the clinical context, these guidelines will be essential to translate research progress into concrete applications, improving the management of many gastroenterological and systemic diseases related to the microbiota,” he added. Microbiologists and clinical laboratory managers may want to follow efforts to promote these guidelines, both within healthcare and as they relate to consumers ordering their own microbiome tests. (Photo copyright: Agostino Gemelli University.)
Our Second Brain
The gut microbiome consists of the microorganisms that reside in the human gut and the small and large intestines. This ecosystem plays a major role in an individual’s health as it aids in digestion and metabolism. It also helps control inflammation and can strengthen the immune system.
“[The gut microbiome] contains all the microbes that reside within our intestinal tract. And those microbes are comprised of bacteria, fungi, yeast and viruses,” said Gail Cresci, PhD, RD, Director, Nutrition Research Center for Human Nutrition at the Cleveland Clinic in a Health Essentials article.
“What we’ve learned over the years is that there’s a lot of crosstalk between your gut microbiome and your body,” she added.
A healthy gut microbiome is imperative for good human health. An unhealthy gut microbiome can lead to certain diseases and even have a negative effect on mental health and mood.
“Your gut health is so important because studies really do indicate that our gut health plays a huge role in our overall health,” stated Kristin Kirkpatrick, MS, RDN, a dietician at the Cleveland Clinic Department of Wellness and Preventative Medicine, in the article. “It impacts our risk of chronic conditions, our ability to manage our weight, even our immune system. … There is so much attention and research on the microbiome and gut health now that experts often refer to it as the ‘second brain.’”
Future of Microbiome Testing
In their consensus document, the scientists wrote, “We convened an international multidisciplinary expert panel to standardize best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field.”
The team’s intent is to provide guidelines and define quality standards and accuracy for microbiome testing to ensure consumers are receiving factual information.
“In recent years, the intestinal microbiota has taken on a key role as a diagnostic, prognostic and therapeutic tool,” said gastroenterology surgeon Serena Porcari, MD, of Gemelli University Hospital in Italy, in the Gemelli news release. “From this point of view, the first step, for a targeted modulation of the microbiota itself, is to obtain a standardization of its analysis, regulated according to the definition of minimum criteria for performing the test.”
The team also evaluated disparities between various tests and anticipated what lies ahead for the future of microbiome testing. In addition, they assessed ways to minimize inappropriate testing and established a framework for the development of evidence-based testing and the use of human microbiota diagnostics in clinical medicine.
“This consensus document represents a crucial step towards bringing order to the current panorama of diagnostic tests on the intestinal microbiota,” said Maurizio Sanguinetti, MD, director of the department of laboratory and hematological sciences at Gemelli Polyclinic Foundation, in the news release. “The diagnostic characterization of the intestinal microbiota must be based on rigorous standards, in order to guarantee reliable and clinically useful results. It is not a simple laboratory test, but a complex tool that requires a deep understanding of microbial dynamics and their impact on human health.
“This is why these analyses must be conducted by highly qualified personnel with specific expertise in clinical microbiology and bioinformatics,” he emphasized. “In our microbiology laboratory at the Fondazione Policlinico Gemelli, we already apply diagnostic tests on the intestinal microbiota following the principles and best practices outlined in the document.
“It is essential to invest in the training of future physicians and microbiologists so that they acquire the necessary skills to correctly interpret the results of these tests and apply them effectively in clinical practice. This document provides a valuable basis to guide not only the current use of the tests, but also their future development, always with a view to evidence-based and personalized medicine,” Sanguinetti concluded.
With popularity of microbiome testing on the rise, it’s important that microbiologists and clinical laboratory professionals stay informed on the latest developments in the field of microbiome diagnostics to protect healthcare consumers and their patients.
Although it is a non-specific procedure that does not identify specific health conditions, it could lead to new biomarkers that clinical laboratories could use for predictive healthcare
Researchers from the Mayo Clinic recently used artificial intelligence (AI) to develop a predictive computational tool that analyzes an individual’s gut microbiome to identify how a person may experience improvement or deterioration in health.
Dubbed the Gut Microbiome Wellness Index 2 (GMWI2), Mayo’s new tool does not identify the presence of specific health conditions but can detect even minor changes in overall gut health.
Built on an earlier prototype, GMWI2 “demonstrated at least 80% accuracy in differentiating healthy individuals from those with any disease,” according to a Mayo news release. “The researchers used bioinformatics and machine learning methods to analyze gut microbiome profiles in stool samples gathered from 54 published studies spanning 26 countries and six continents. This approach produced a diverse and comprehensive dataset.”
“Our tool is not intended to diagnose specific diseases but rather to serve as a proactive health indicator,” said senior study author Jaeyun Sung, PhD (above), a computational biologist at the Mayo Clinic Center for Individualized Medicine: Microbiomics Program in the news release ease. “By identifying adverse changes in gut health before serious symptoms arise, the tool could potentially inform dietary or lifestyle modifications to prevent mild issues from escalating into more severe health conditions, or prompt further diagnostic testing.” For microbiologists and clinical laboratory managers, this area of new knowledge about the human microbiome may lead to multiplex diagnostic assays. (Photo copyright: Mayo Clinic.)
Connecting Specific Diseases with Gut Microbiome
Gut bacteria that resides in the gastrointestinal tract consists of trillions of microbes that help regulate various bodily functions and may provide insights regarding the overall health of an individual. An imbalance in the gut microbiome is associated with an assortment of illnesses and chronic diseases, including cardiovascular issues, digestive problems, and some cancers and autoimmune diseases.
To develop GMWI2, the Mayo scientists provided the machine-learning algorithm with data on microbes found in stool samples from approximately 8,000 people collected from 54 published studies. They looked for the presence of 11 diseases, including colorectal cancer and inflammatory bowel disease (IBS). About 5,500 of the subjects had been previously diagnosed with one of the 11 diseases, and the remaining people did not have a diagnosis of the conditions.
The scientists then tested the efficacy of GMWI2 on an additional 1,140 stool samples from individuals who were diagnosed with conditions such as pancreatic cancer and Parkinson’s disease, compared with those who did not have those illnesses.
The algorithm gives subjects a score between -6 and +6. People with a higher GMWI2 score have a healthier microbiome that more closely resembles individuals who do not have certain diseases.
Likewise, a low GMWI2 score suggests the individual has a gut microbiome that is similar to those who have specific illnesses.
Highly Accurate Results
According to their study, the researchers determined that “GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence,” they wrote in Nature Communications.
Launched in 2020, the original GMWI (Gut Microbiome Wellness Index) was trained on a much smaller number of samples but still showed similar results.
The researchers tested the enhanced GMWI2 algorithm across various clinical schemes to determine if the results were similar. These scenarios included individuals who had previous fecal microbiota transplants and people who had made dietary changes or who had exposure to antibiotics. They found that their improved tool detected changes in gut health in those scenarios as well.
“By being able to answer whether a person’s gut is healthy or trending toward a diseased state, we ultimately aim to empower individuals to take proactive steps in managing their own health,” Sung said in the news release.
The Mayo Clinic team is developing the next version of their tool, which will be known as the Gut Microbiome Wellness Index 3. They plan to train it on at least 12,000 stool samples and use more sophisticated algorithms to decipher the data.
More research and studies are needed to determine the overall usefulness of Mayo’s Gut Microbiome Wellness Index and its marketability. Here is a world-class health institution disclosing a pathway/tool that analyzes the human microbiome to identify how an individual may be experiencing either an improvement in health or a deterioration in health.
The developers believe it will eventually help physicians determine how patients’ conditions are improving or worsening by comparing the patients’ microbiomes to the profiles of other healthy and unhealthy microbiomes. As this happens, it would create a new opportunity for clinical laboratories to perform the studies on the microbiomes of patients being assayed in this way by their physicians.
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.
“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 Akkermansiaglycosyl 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.
Is it possible that there is a connection between an individual’s gut microbiota and the ability to fight off gastrointestinal (GI) cancer? Findings from a preliminary research study performed by researchers in South Korea suggest that a link between the two may exist and that fecal microbiota transplants (FMTs) may enhance the efficacy of immunotherapies for GI cancer patients.
The proof-of-concept clinical trial, conducted at the Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea, analyzed how an FMT could help 13 patients with metastatic solid tumors that were resistant to the anti-PD-1 antibody drug known as nivolumab (Opdivo). Anti-PD-1 drugs are immunotherapies that help treat cancer by improving an individual’s immune response against cancer cells.
Four of the trial participants had gastric cancer, five had esophageal cancer, and the remaining four had hepatocellular carcinoma. The patients were given a colonoscopy to implant the FMTs. The recipients also received antibiotics to reduce the response of their existing microbiotas.
The FMT donors also had gastric cancer, esophageal cancer, or hepatocellular carcinoma. Prior to donating their fecal matter, the donors experienced complete or partial response to the anti-PD-1 drugs nivolumab or pembrolizumab (Keytruda) for at least six months after receiving initial treatments.
“This research highlights the complex interplay between beneficial and detrimental bacteria within the gut microbiota in determining treatment outcomes,” co-senior study author Hansoo Park, MD, PhD, Assistant Professor, Biomedical Science and Engineering, Gwangju Institute of Science and Technology, told The ASCO Post. “While the connection between gut microbiota and immune response to cancer therapy has been a growing area of interest, our study provides concrete evidence and new avenues for improving treatment outcomes in a broader range of cancers,” he added. Further studies may confirm the need for microbiome testing by clinical laboratories to guide clinicians treating patients with colon cancers. (Photo copyright: Gwangju Institute of Science and Technology.)
Surprising Results
Fecal material for an FMT procedure combines donated fecal matter with a sterile saline solution which is then filtered to produce a liquid solution. That solution is then administered to the recipient via colonoscopy, upper GI endoscopy, enema, or an oral capsule. The solution may also be frozen for later use.
Upon analyzing the recipients, the scientists found that six of the patients (46.2%) who had experienced resistance to immunotherapies for their cancers, benefitted from the FMTs.
“Both donors were long-lasting, good responders to anti-PD-1 inhibitors, but because we did not yet know the causative bacteria responsible for the [FMT] response, we could not predict whether the treatment would be effective,” she added.
The researchers also determined that the presence of a bacterial strain known as Prevotella merdae helped to improve the effectiveness of the FMTs, while two strains of bacteria—Lactobacillus salivarius and Bacteroides plebeius (aka, Phocaeicola plebeius)—had a detrimental impact on the transplants.
Challenges to Widespread Adoption of FMTs
The researchers acknowledge there are challenges in widespread acceptance and use of FMTs in treating cancers but remain optimistic about the possibilities.
“Developing efficient and cost-effective methods for production and distribution is necessary for widespread adoption,” Sook Ryun Park told The ASCO Post. “Addressing these challenges through comprehensive research and careful planning will be essential for integrating FMT into the standard of care for cancer treatment.”
More research and clinical trials are needed before this use of FMTs can be utilized in clinical settings. However, the study does demonstrate that the potential benefits of FMTs may improve outcomes in patients with certain cancers. As this happens, microbiologists may gain a new role in analyzing the microbiomes of patients with gastrointestinal cancers.
“By examining the complex interactions within the microbiome, we hope to identify optimal microbial communities that can be used to enhance cancer treatment outcomes,” Hansoo Park told The ASCO Post. “This comprehensive approach will help us understand how the microbial ecosystem as a whole contributes to therapeutic success.”
Clinical laboratory scientists and microbiologists could play a role in helping doctors explain to patients the potential dangers of do-it-yourself medical treatments
Be careful what you wish for when you perform do-it-yourself (DIY) medical treatments. That’s the lesson learned by a woman who was seeking relief for irritable bowel syndrome (IBS). When college student Daniell Koepke did her own fecal transplant using poop from her brother and her boyfriend as donors her IBS symptoms improved, but she began to experience medical conditions that afflicted both fecal donors.
“It’s possible that the bacteria in the stool can influence inflammation in the recipient’s body, by affecting their metabolism and activating their immune response,” microbial ecologist Jack Gilbert, PhD, Professor and Associate Vice Chancellor at University of California San Diego (UC San Diego) told Business Insider. “This would cause shifts in their hormonal activity, which could promote the bacteria that can cause acne on the skin. We nearly all have this bacterium on skin, but it is often dormant,” he added.
A Fecal Microbiota Transplant (FMT) is a procedure where stool from a healthy donor is transplanted into the microbiome of a patient plagued by a certain medical condition.
Our guts are home to trillions of microorganisms (aka, microbes), known as the gut microbiota, that serve many important functions in the body. The microbiome is a delicate ecosystem which can be pushed out of balance when advantageous microbes are outnumbered by unfavorable ones. An FMT is an uncomplicated and powerful method of repopulating the microbiome with beneficial microbes.
“With fecal microbiome transplants there is really compelling evidence, but the science is still developing. We’re still working on if it actually has benefits for wider populations and if the benefit is long-lasting,” said Gilbert in a Netflix documentary titled, “Hack Your Health: The Secrets of Your Gut.”
“The microbial community inside our gut can have surprising influences on different parts of our body,” microbial ecologist Jack Gilbert, PhD (above), of the Gilbert Lab at University of California San Diego told Business Insider. “Stools are screened before clinical FMTs, and anything that could cause major problems, such as certain pathogens, would be detected. When you do this at home, you don’t get that kind of screening.” Doctors and clinical laboratories screening patients for IBS understand the dangers of DIY medical treatments. (Photo copyright: University of California San Diego.)
Changing Poop Donors
When Koepke began experiencing symptoms of IBS including indigestion, stabbing pains from trapped gas and severe constipation, she initially turned to physicians for help.
In the Netflix documentary, Koepke stated that she was being prescribed antibiotics “like candy.” Over the course of five years, she completed six rounds of antibiotics per year, but to no avail.
She also changed her diet, removing foods that were making her symptoms worse. This caused her to lose weight and she eventually reached a point where she could only eat 10 to 15 foods.
“It’s really hard for me to remember what it was like to eat food before it became associated with anxiety and pain and discomfort,” she said.
In an attempt to relieve her IBS symptoms, Koepke made her own homemade fecal transplant pills using donated stool from her brother. After taking them her IBS symptoms subsided and she slowly gained weight. But she developed hormonal acne just like her brother.
Koepke then changed donors, using her boyfriend’s poop to make new fecal transplant pills. After she took the new pills, her acne dissipated but she developed depression, just like her boyfriend.
“Over time, I realized my depression was worse than it’s ever been in my life,” Koepke stated in the documentary.
She believes the microbes that were contributing to her boyfriend’s depression were also transplanted into her via the fecal transplant pills. When she reverted to using her brother’s poop, her depression abated within a week.
Gilbert told Business Insider his research illustrates that people who suffer from depression are lacking certain bacteria in their gut microbiome.
“She may have had the ‘anti-depressant’ bacteria in her gut, but when she swapped her microbiome with his, her anti-depressant bacteria got wiped out,” he said.
FDA Approves FMT Therapy for Certain Conditions
Typically, the fecal material for an FMT procedure performed by a doctor comes from fecal donors who have been rigorously screened for infections and diseases. The donations are mixed with a sterile saline solution and filtered which produces a liquid solution. That solution is then administered to a recipient or frozen for later use.
On November 30, 2022, the US Food and Drug Administration (FDA) approved the first FMT therapy, called Rebyota, for the prevention of Clostridioides difficile (C. diff.) in adults whose symptoms do not respond to antibiotic therapies. Rebyota is a single-dose treatment that is administered rectally into the gut microbiome at a doctor’s office.
Then, in April of 2023, the FDA approved the use of a medicine called Vowst, which is the first oral FMT approved by the FDA.
According to the Cleveland Clinic, scientists are exploring the possibility that fecal transplants may be used as a possible treatment for many health conditions, including:
Doctors and clinical laboratories know that do-it-yourself medicine is typically not a good idea for obvious reasons. Patients seldom appreciate all the implications of the symptoms of an illness, nor do they fully understand the potentially dangerous consequences of self-treatment. Scientists are still researching the benefits of fecal microbiota transplants and hope to discover more uses for this treatment.
