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.
As this therapeutic approach gains regulatory approval, clinical laboratory tests to determine condition of patient’s gut microbiota and monitor therapy will be needed
Some developments in the clinical laboratory industry are less about diagnostic tests and more about novel approaches to therapy. Such is the case with a new carbon bead technology developed by researchers from University College London (UCL) and the Royal Free Hospital intended to remove harmful bacteria toxins from the gut before they leak to the liver. The macroporous beads, which come in small pouches, are delivered orally and could be utilized in the future to treat a number of diseases.
Why is this relevant? Once a new treatment is accepted for clinical use, demand increases for a clinical laboratory test that confirms the therapy will likely work and to monitor its progress.
In collaboration with Yaqrit, a UK-based life sciences company that develops treatments for chronic liver disease, the UCL and Royal Free Hospital scientists engineered the carbon beads—known as CARBALIVE—to help restore gut health. They measured the technology’s impact on liver, kidney, and brain function in both rats and mice.
“The influence of the gut microbiome on health is only just beginning to be fully appreciated,” said Rajiv Jalan, PhD, Professor of Hepatology at UCL in a press release. “When the balance of the microbiome is upset, ‘bad’ bacteria can proliferate and out-compete the ‘good’ bacteria that keeps the gut healthy.
“One of the ways [the ‘bad’ bacteria] do this is by excreting endotoxin, toxic metabolites, and cytokines that transform the gut environment to make it more favorable to them and hostile to good bacteria,” he continued. “These substances, particularly endotoxin, can trigger gut inflammation and increase the leakiness of the gut wall, resulting in damage to other organs such as the liver, kidneys, and brain.”
“I have high hopes that the positive impact of these carbon beads in animal models will be seen in humans, which is exciting not just for the treatment of liver disease but potentially any health condition that is caused or exacerbated by a gut microbiome that doesn’t work as it should,” said Rajiv Jalan, PhD (above), Professor of Hepatology, University College London, in a press release. “This might include conditions such as irritable bowel syndrome (IBS), for example, which is on the rise in many countries.” Though not a clinical laboratory diagnostic test, new therapies like CARBALIVE could be a boon to physicians treating patients with IBS and other gastrointestinal conditions.
Developing the Carbon Beads
The team discovered CARBALIVE is effective in the prevention of liver scarring and injury in animals with cirrhosis when ingested daily for several weeks. They also found a reduced mortality rate in test animals with acute-on-chronic-liver-failure (ACLF).
After achieving success with CARBALIVE in animals, the researchers tested the technology on 28 cirrhosis patients. The carbon beads proved to be safe for humans and had inconsequential side effects.
“In cirrhosis, a condition characterized by scarring of the liver, it is known that inflammation caused by endotoxins can exacerbate liver damage,” Jalan explained. “Part of the standard treatment for cirrhosis is antibiotics aimed at controlling bad bacteria, but this comes with the risk of antibiotic resistance and is only used in late-stage disease.”
The beads, which are smaller than a grain of salt, contain an exclusive physical structure that absorbs large and small molecules in the gut. They are intended to be taken with water at bedtime as harmful bacteria is more likely to circulate through the body at night which could result in damage. The carbon beads do not kill bacteria, which decreases the risk of antibiotic resistance. They eventually pass through the body as waste.
“They work by absorbing the endotoxins and other metabolites produced by ‘bad’ bacteria in the gut, creating a better environment for the good bacteria to flourish and helping to restore microbiome health,” said Michal Kowalski, M.Sc.Eng, Director and VP of Operations at Yaqrit, in the UCL news release.
“This prevents these toxins from leaching into other areas of the body and causing damage, as they do in cirrhosis,” he added. “The results in animal models are very positive, with reduction in gut permeability, liver injury, as well as brain and kidney dysfunction.”
Additional Research
The researchers plan to perform further clinical trials in humans to determine if the carbon beads are effective at slowing the progression of liver disease. If the benefits that were observed in lab animals prove to be compelling in humans, the technology may become an invaluable tool for the treatment of liver disease and other diseases associated with poor microbiome health in the future.
According to the American Liver Foundation, 4.5 million adults in the US have been diagnosed with liver disease. However, it is estimated that 80 to 100 million adults have some form of fatty liver disease and are unaware of it. Liver disease was the 12th leading cause of death in the US in 2020 with 51,642 adults perishing from the disease that year.
According to BMC Public Health, globally there were 2.05 million new cases of liver cirrhosis diagnosed in 2019. In that year, 1.47 million people around the world died from the disease.
More research and clinical studies are needed before this novel technology can be used clinically. When and if that happens, the demand for clinical laboratory tests that measure microbiome deficiencies and monitor patient progress during therapy will likely be high.
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.
Though smartphone apps are technically not clinical laboratory tools, anatomic pathologists and medical laboratory scientists (MLSs) may be interested to learn how health information technology (HIT), machine learning, and smartphone apps are being used to assess different aspects of individuals’ health, independent of trained healthcare professionals.
The issue that the Cedars Sinai researchers were investigating is the accuracy of patient self-reporting. Because poop can be more complicated than meets the eye, when asked to describe their bowel movements patients often find it difficult to be specific. Thus, use of a smartphone app that enables patients to accurately assess their stools in cases where watching the function of their digestive tract is relevant to their diagnoses and treatment would be a boon to precision medicine treatments of gastroenterology diseases.
“This app takes out the guesswork by using AI—not patient input—to process the images (of bowel movements) taken by the smartphone,” said gastroenterologist Mark Pimentel, MD (above), Executive Director of Cedars-Sinai’s Medically Associated Science and Technology (MAST) program and principal investigator of the study, in a news release. “The mobile app produced more accurate and complete descriptions of constipation, diarrhea, and normal stools than a patient could, and was comparable to specimen evaluations by well-trained gastroenterologists in the study.” (Photo copyright: Cedars-Sinai.)
Pros and Cons of Bristol Stool Scale
In their paper, the scientists discussed the Bristol Stool Scale (BSS), a traditional diagnostic tool for identifying stool forms into seven categories. The seven types of stool are:
Type 1: Separate hard lumps, like nuts (difficult to pass).
Type 2: Sausage-shaped, but lumpy.
Type 3: Like a sausage, but with cracks on its surface.
Type 4: Like a sausage or snake, smooth and soft (average stool).
Type 5: Soft blobs with clear cut edges.
Type 6: Fluffy pieces with ragged edges, a mushy stool (diarrhea).
Type 7: Watery, no solid pieces, entirely liquid (diarrhea).
But even with the BSS, things can get murky for patients. Inaccurate self-reporting of stool forms by people with IBS and diarrhea can make proper diagnoses difficult.
“The problem is that whenever you have a patient reporting an outcome measure, it becomes subjective rather than objective. This can impact the placebo effect,” gastroenterologist Mark Pimentel, MD, Executive Director of Cedars-Sinai’s Medically Associated Science and Technology (MAST) program and principal investigator of the study, told Healio.
Thus, according to the researchers, AI algorithms can help with diagnosis by systematically doing the assessments for the patients, News Medical reported.
30,000 Stool Images Train New App
To conduct their study, the Cedars-Sinai researchers tested an AI smartphone app developed by Dieta Health. According to Health IT Analytics, employing AI trained on 30,000 annotated stool images, the app characterizes digital images of bowel movements using five parameters:
BSS,
Consistency,
Edge fuzziness,
Fragmentation, and
Volume.
“The app used AI to train the software to detect the consistency of the stool in the toilet based on the five parameters of stool form, We then compared that with doctors who know what they are looking at,” Pimentel told Healio.
AI Assessments Comparable to Doctors, Better than Patients
According to Health IT Analytics, the researchers found that:
AI assessed the stool comparable to gastroenterologists’ assessments on BSS, consistency, fragmentation, and edge fuzziness scores.
AI and gastroenterologists had moderate-to-good agreement on volume.
AI outperformed study participant self-reports based on the BSS with 95% accuracy, compared to patients’ 89% accuracy.
Additionally, the AI outperformed humans in specificity and sensitivity as well:
Specificity (ability to correctly report a negative result) was 27% higher.
Sensitivity (ability to correctly report a positive result) was 23% higher.
“A novel smartphone application can determine BSS and other visual stool characteristics with high accuracy compared with the two expert gastroenterologists. Moreover, trained AI was superior to subject self-reporting of BSS. AI assessments could provide more objective outcome measures for stool characterization in gastroenterology,” the Cedars-Sinai researchers wrote in their paper.
“In addition to improving a physician’s ability to assess their patients’ digestive health, this app could be advantageous for clinical trials by reducing the variability of stool outcome measures,” said gastroenterologist Ali Rezaie, MD, study co-author and Medical Director of Cedars-Sinai’s GI Motility Program in the news release.
The researchers plan to seek FDA review of the mobile app.
Opportunity for Clinical Laboratories
Anatomic pathologists and clinical laboratory leaders may want to reach out to referring gastroenterologists to find out how they can help to better serve gastro patients. As the Cedars-Sinai study suggests, AI smartphone apps can perform BSS assessments as good as or better than humans and may be useful tools in the pursuit of precision medicine treatments for patient suffering from painful gastrointestinal disorders.
