Collected data could give healthcare providers and clinical laboratories a practical view of individuals’ oral microbiota and lead to new diagnostic assays
When people hear about microbiome research, they usually think of the study of gut bacteria which Dark Daily has covered extensively. However, this type of research is now expanding to include more microbiomes within the human body, including the oral microbiome—the microbiota living in the human mouth.
One example is coming from Genefitletics, a biotech company based in New Delhi, India. It recently launched ORAHYG, the first and only (they claim) at-home oral microbiome functional activity test available in Asia. The company is targeting the direct-to-consumer (DTC) testing market.
According to the Genefitletics website, the ORAHYG test can decode the root causes of:
“Using oral microbial gene expression sequencing technology and its [machine learning] model, [Genefitletics] recently debuted its oral microbiome gene expression solution, which bridges the gap between dentistry and systemic inflammation,” ETHealthworld reported.
“The molecular insights from this test would give an unprecedented view of functions of the oral microbiome, their interaction with gut microbiome and impact on metabolic, cardiovascular, cognitive, skin, and autoimmune health,” BioSpectrum noted.
“Microbes, the planet Earth’s original inhabitants, have coevolved with humanity, carry out vital biological tasks inside the body, and fundamentally alter how we think about nutrition, medicine, cleanliness, and the environment,” Sushant Kumar (above), founder and CEO of Genefitletics, told the Economic Times. “This has sparked additional research over the past few years into the impact of the trillions of microorganisms that inhabit the human body on our health and diverted tons of funding into the microbiome field.” Clinical laboratories may eventually see an interest and demand for testing of the oral microbiome. (Photo copyright: ETHealthworld.)
Imbalanced Oral Microbiome Can Trigger Disease
The term microbiome refers to the tiny microorganisms that reside on and inside our bodies. A high colonization of these microorganisms—including bacteria, fungi, yeast, viruses, and protozoa—live in our mouths.
“Mouth is the second largest and second most diverse colonized site for microbiome with 770 species comprising 100 billion microbes residing there,” said Sushant Kumar, founder and CEO of Genefitletics, BioSpectrum reported. “Each place inside the mouth right from tongue, throat, saliva, and upper surface of mouth have a distinctive and unique microbiome ecosystem. An imbalanced oral microbiome is said to trigger onset and progression of type 2 diabetes, arthritis, heart diseases, and even dementia.”
The direct-to-consumer ORAHYG test uses a saliva sample taken either by a healthcare professional or an individual at home. That sample is then sequenced through Genefitletics’ gene sequencing platform and the resulting biological data set added to an informatics algorithm.
Genefitletics’ machine-learning platform next converts that information into a pre-symptomatic molecular signature that can predict whether an individual will develop a certain disease. Genefitletics then provides that person with therapeutic and nutritional solutions that can suppress the molecules that are causing the disease.
“The current industrial healthcare system is really a symptom care [system] and adopts a pharmaceutical approach to just make the symptoms more bearable,” Kumar told the Economic Times. “The system cannot decode the root cause to determine what makes people develop diseases.”
Helping People Better Understand their Health
Founded in 2019, Genefitletics was created to pioneer breakthrough discoveries in microbial science to promote better health and increase longevity in humans. The company hopes to unravel the potential of the oral microbiome to help people fend off illness and gain insight into their health.
“Microorganisms … perform critical biological functions inside the body and transform our approach towards nutrition, medicine, hygiene and environment,” Kumar told CNBC. “It is important to understand that an individual does not develop a chronic disease overnight.
“It starts with chronic inflammation which triggers pro-inflammatory molecular indications. Unfortunately, these molecular signatures are completely invisible and cannot be measured using traditional clinical grade tests or diagnostic investigations,” he added. “These molecular signatures occur due to alteration in gene expression of gut, oral, or vaginal microbiome and/or human genome. We have developed algorithms that help us in understanding these alterations way before the clinical symptoms kick in.”
Genefitletics plans to utilize individuals’ collected oral microbiome data to determine their specific nutritional shortcomings, and to develop personalized supplements to help people avoid disease.
The company also produces DTC kits that analyze gut and vaginal microbiomes as well as a test that is used to evaluate an infant’s microbiome.
“The startup wants to develop comparable models to forecast conditions like autism, PCOS [polycystic ovarian syndrome], IBD [Inflammatory bowel disease], Parkinson’s, chronic renal [kidney] disease, anxiety, depression, and obesity,” the Economic Times reported.
Time will tell whether the oral microbiome tests offered by this company prove to be clinically useful. Certainly Genefitletics hopes its ORAHYG test can eventually provide healthcare providers—including clinical laboratory professionals—with a useful view of the oral microbiome. The collected data might also help individuals become aware of pre-symptomatic conditions that make it possible for them to seek confirmation of the disease and early treatment by medical professionals.
Studying gut bacteria continues to intrigue investors, but can the results produce viable diagnostic data for healthcare providers?
Even as microbiologists and clinical pathologists closely watch research into the human microbiome and anticipate study findings that could lead to new medical laboratory tests based on microbiome testing, there are entrepreneurs ready to tout the benefits of microbiome testing to consumers. That’s the impetus behind an announced deal between a microbiome testing company and a national pharmacy chain.
That deal involves health startup Viome Life Sciences, which recently closed a $86.5 million Series C funding round to support research and development of its consumer health at-home test kits, and CVS, which will sell Viome’s Gut Intelligence Test at 200 of the pharmacy company’s retail locations nationwide, according to an August press release.
“Founded seven years ago by serial entrepreneur Naveen Jain, Viome sells at-home kits that analyze the microbial composition of stool samples and provide food recommendations, as well as supplements and probiotics. Viome says it is the first company to sell gut tests at CVS, both online and in-store. The tests will sell for $179,” GeekWire reported.
Investors appear to be intrigued by these types of opportunities. To date, Viome has raised a total of $175 million.
“In a world where healthcare has often been reactive, treating symptoms and targeting diseases only after they manifest, Viome is pioneering a transformative shift by harnessing the innate power of food and nutrition,” stated Naveen Jain (above), Founder and CEO of Viome, in a press release. “Our mission is not just to prolong life but to enrich it, enabling everyone to thrive in health and vitality.” But some microbiologists and clinical laboratory scientists would consider that the current state of knowledge about the human microbiome is not well-developed enough to justify offering direct-to-consumer microbiology tests that encourage consumers to purchase nutritional products. (Photo copyright: Viome Life Sciences.)
Empowering People to Make Informed Decisions about Their Health
Established in 2016, Bellevue, Washington-based Viome produces and sells, among other tests, its Gut Intelligence at-home test kit, which analyzes the microbial composition of stool samples. This kit relies on RNA sequencing to detect bacteria and other elements present in the gut, such as yeasts and viruses.
The genetic data is then entered into an artificial intelligence (AI) algorithm to provide individuals with information regarding their personal gut health. Viome partnered with Los Alamos National Laboratory to create their AI platform. The company has collected more than 600,000 test samples to date.
“We are the only company that looks at the gene expression and what these microbes are doing,” said Naveen Jain, Founder and CEO of Viome in the press release.
Viome uses technology combined with science to determine the optimal outcomes for each individual consumer based on his or her unique human and microbial gene expression. The data derived from the microbiome is also utilized to offer nutritional recommendations and supplement advice to test takers.
“At Viome, we’re empowering our customers with an individualized nutrition strategy, cutting through the noise of temporary trends and one-size-fits-all advice,” Jain added. “We’re on a journey to redefine aging itself, and we’re invigorated by the support of our investors and customers. Together, we’re building pathways to wellness that hold the potential to enhance the lives of billions of fellow humans across the globe.”
Manipulating Microbiome through Diet
Some scientists, however, are not sold on the idea of microbiome test kits and the data they offer to healthcare providers for treating illnesses.
“The best thing anybody can do for their microbiome is to eat a healthy diet. That’s the best way of manipulating your microbiome,” David Suskind, MD, a gastroenterologist at Seattle Children’s Hospital and Professor of Pediatrics at the University of Washington, told GeekWire.
Verdu, GeekWire reported, added that “there needs to be standardization of protocols and better understanding of microbiome function in health and disease.”
“Recommendations for such commercial kits would have to be based on evidence-based guidelines, which currently do not exist,” she told GeekWire.
Nevertheless, Jain remains positive about the value of microbiome testing. “The future of medicine will be delivered at home, not at the hospital. And the medicines of the future are going to come from a farm, not a pharmacy,” he told GeekWire.
Other Viome At-home Tests
According to a paper published in the journal Therapeutic Advances in Gastroenterology titled, “Role of the Gut Microbiota in Health and Chronic Gastrointestinal Disease: Understanding a Hidden Metabolic Organ,” the human gut contains trillions of microbes, and no two people share the exact same microbiome composition. This complex community of microbial cells influences human physiology, metabolism, nutrition and immune function, and performs a critical role in overall health.
CVS currently sells Viome’s “Gut Intelligence Health Insights Plus Personalized Nutrition Plan” on its website for $149.99. Prices may vary from online to in-store. The test is intended for individuals who want to monitor and address gut imbalances or health symptoms, such as:
Constipation
Diarrhea
Stomach pain
Bloating
Heartburn
Itchy skin
Trouble maintaining a healthy weight
Viome sells the Gut Intelligence Test for $179 on its own website, as well as the following health tests:
Viome also sell precision probiotics and prebiotics, as well as supplements and oral health lozenges.
Gut microbiome testing kits, such as the one from Viome, typically require the collection of a stool sample. Healthcare consumers have in the past been reluctant to perform such testing, but as more information regarding gut health is published, that reluctance may diminish.
Clinical laboratories also have a stake in the game. Dynamic direct to consumer at-home testing has the potential to generate revenue for clinical laboratories, while helping consumers who want to monitor different aspects of their health. But this would be an adjunct to the primary mission of medical laboratories to provide testing services to local physicians and their patients.
Technology enables sampling of an individual’s microbiome over time to observe changes associated with different illnesses or different diets
There is now a pill-sized device that can non-invasively collect and deliver a sample of gut bacteria taken directly from specific areas of a person’s gastrointestinal (GI) tract. One benefit of this new technology is that it can collect samples from the upper digestive system. Although not ready for clinical use, this is the kind of technology that would enable microbiologists and clinical laboratory scientists to add more microbiome assays to their test menu.
Researchers at Stanford University, Envivo Bio, and the University of California, Davis (UC Davis) have developed a vitamin capsule-sized device—dubbed CapScan—that can measure the microbial, viral, and bile acid profiles contained in the human intestines as it passes through on its way to being expelled.
Currently, scientists rely on stool samples to collect similar data as they are easy to gather and readily available. However, stool samples may not provide the most accurate analysis of the various microorganisms that reside in the human gut.
“Measuring gut metabolites in stool is like studying an elephant by examining its tail,” said Dari Shalon, PhD, Founder and CEO at Envivo Bio, one of the authors of the study, in a UC Davis news release. “Most metabolites are made, transformed, and utilized higher up in the intestines and don’t even make it into the stool. CapScan gives us a fuller picture of the gut metabolome and its interactions with the gut microbiome for the first time.” Shalon is the inventor of the CapScan device.
This demonstrates how technological advancements are giving scientists new diagnostic tools to guide selection of therapies and to monitor a patient’s progress.
Microbiologists will take a special interest in this published study because, once confirmed by further studies, it would provide microbiology laboratories and clinical labs with a new way to collect samples. In clinical laboratories throughout the country, handling fecal specimens is considered an unpleasant task. Once cleared for clinical use, devices like CapScan would be welcomed because the actual specimen would be contained within the capsule, making it a cleaner, less smelly specimen to handle than conventional fecal samples.
“This capsule and reports are the first of their kind,” said Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis, in a news release. “All other studies on human gut microbiota focused on stool as a surrogate for colon metabolism. However, of course, the fact is that 90% of human digestion happens in the upper intestine, not the colon.” Clinical laboratories have long worked with stool samples to perform certain tests. If CapScan proves clinically viable, labs may soon have a new diagnostic tool. (Photo copyright: UC Davis.)
Collecting Small Intestine Microbiota
Human digestion occurs mostly in the small intestine where enzymes break down food particles so they can later be absorbed through the gut wall and processed in the body. Stool samples, however, only sample the lower colon and not the small intestine. This leaves out vital information about a patient.
“The small intestine has so far only been accessible in sedated people who have fasted, and that’s not very helpful,” Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis and one of the study authors, said in the news release.
According to their Nature paper, to perform their research the team recruited 15 healthy adults to participate in the study. Each participant swallowed four CapScan “pills,” either twice daily or on two consecutive days. The pills were designed to respond to different pH (potential of hydrogen) levels.
Each pill’s pH-sensitive outer coating enables scientists to select which area of the intestinal tract to sample. The outer coating dissolves at a certain point as it travels from the upper intestine to the colon. When this happens, a one-way valve gathers miniscule amounts of biofluids into a tiny, inflatable bladder. Once full, the bladder seals shut and the CapScan continues its journey until it is recovered in the stool. The researchers then genetically sequenced the RNA from the collected samples.
The scientists discovered that the microbiome varied substantially at distinctive sections of the GI tract. When compared to collected stool samples, the researchers determined that traditional stool sampling could not capture that variability.
“There’s enormous potential as you think about how the environment is changing as you go down the intestinal tract,” Kerwyn Huang, PhD, Professor of Bioengineering and of Microbiology and Immunology at Stanford, one of the authors of the study, told Drug Discovery News. “Identifying how something like diet or disease affects the variation in the individual microbiome may even provide the potential to start discovering these important health associations.”
The genetic sequencing also revealed which participants had taken antibiotics within one to five months before the study because their data was so incongruous with the other participants. Those individuals had distinctive differences in their microbiome and bile acid composition, which illustrates that antibiotics can potentially affect gut bacteria even months after being taken.
Researchers Use Multiple ‘Omics’ Approach
The researchers used “multiomics” to analyze the samples. They identified the presence of 2,000 metabolites and found associations between metabolites and diet.
According to the Envivo Bio website, the CapScan allows for the regional measurement of:
“Overall, this device can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease,” Fiehn said in the press release.
Future of Collecting Gut Bacteria
Using CapScan is a non-invasive procedure that makes it possible to sample an individual’s microbiome once, or to monitor it over time to observe changes associated with different illnesses or diets. Since it takes time for the device to pass through the digestive system, it is not a rapid test, but initial studies show it could be more accurate than traditional clinical laboratory testing.
“This technology makes it natural to think about sampling from many places and many times from one person, and it makes that straightforward and inexpensive,” Huang said.
Advancements in technology continue to provide microbiology and clinical laboratories with new, innovative tools for diagnosing and monitoring diseases, as well as guiding therapy selection by medical professionals. Though more research and clinical studies are needed before a device like the CapScan can be commonly used by medical professionals, it may someday provide a cutting-edge method for collecting microbiome samples.
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.
As scientists gain new insights into the human microbiome and how it influences our health, microbiology labs may gain new diagnostic biomarkers
In a study that took more than five years to complete, researchers from Stanford University have successfully created the first synthetic microbiome model from scratch. The goal of the study was to create a baseline microbiome model so that future studies will have a better understanding of which clinical laboratory tests and medical interventions could be useful for treating specific ailments and improving patient care.
To create their synthetic human microbiome, the Stanford researchers combined 119 species of bacteria, The New York Times reported, adding that “the new synthetic microbiome can even withstand aggressive pathogens and cause mice to develop a healthy immune system, as a full microbiome does.”
According to the National Institute of Health (NIH), the human gut contains trillions of microbes, and no two people share the exact same microbiome composition. This complex community of microbial cells influences human physiology, metabolism, nutrition and immune function, and performs a critical role in overall health.
The Stanford scientists believe researchers now have a common microbiome foundation for future microbial studies.
“We were looking for the Noah’s Ark of bacteria species in the human gut, trying to find the ones that were almost always there in any individual,” said Michael Fischbach, PhD, Associate Professor in the Departments of Bioengineering and Microbiology and Immunology at Stanford University. Future microbial studies that use Stanford’s synthetic human microbiome may develop improved clinical laboratory tests and microbiome therapies. (Photo copyright: Stanford University.)
Creating the ‘Human Community One’ Microbiome
The researchers began their study by examining the gut bacteria makeup of adults involved in the Human Microbiome Project (HMP), an NIH initiative created to sequence the full microbial genomes of more than 300 adults.
The scientists then selected bacterial strains that were present in at least 20% of the HMP individuals. They focused on 104 bacterial species that they grew in individual stocks, and then mixed them into one combined culture to create what they named “Human Community One” (hCom1).
The researchers had to ensure that the final mixture had the stability to maintain a balance where no single species overpowered the rest and could perform all the actions of a natural microbiome.
After being satisfied that the bacterial strains could coexist in a lab situation, the scientists set out to determine if their community would colonize in the gut. To do this, they introduced hCom1 to germ-free mice that are designed to have no natural microbiome.
When transplanted into the mice, the researchers discovered hCom1 was an extremely stable ecosystem, with 98% of the species taking root in the guts of the mice, and the levels of each bacterial species remaining constant over a two-month period.
“We colonized germ-free mice with hCom1 and found that it was stable over time. Its species span six orders of magnitude of relative abundance: from ~10% to less than one in 1,000,000,” Michael Fischbach, PhD, Associate Professor in the Departments of Bioengineering and Microbiology and Immunology at Stanford University and one of the authors of the study, explained on Twitter.
Based on a theory called colonization resistance, the team then introduced a human fecal sample to hCom1 to ensure that all vital microbiome functions would be performed by one or more species. Colonization resistance is the phenomenon where the normal gut microbiome protects itself against invasion by new and often harmful microorganisms. This theory hypothesizes that any bacterium introduced into an existing colony will only survive if it can fill a niche that is not already occupied.
Creating a Second New Microbiome
Some researchers involved in the project were skeptical that introducing human fecal matter to hCom1 would work. They believed it would overtake the synthetic microbiome model.
“The bacterial species in hCom1 had lived together for only a few weeks,” Fischbach explained in a Stanford press release. “Here we were introducing a community that had coexisted for a decade. Some people thought they would decimate our colony.”
However, the scientists found that hCom1 thrived with only about 10% of the cells in the final community originating from the fecal transplant. A few of the original bacterial species died off and approximately 20 new bacterial species were able to successfully colonize hCom1. They ultimately catalogued 119 bacterial strains present in the colony after the transplant and dubbed the new microbiome “Human Community Two” (hCom2).
To further prove the functionality of their synthetic microbiome, the team then introduced an Escherichia coli (E. coli) sample to mice colonized with hCom2 and found that they were able to resist infection.
“Mice colonized by hCom2 look normal immunologically, have similar microbiome-derived metabolites, and exert colonization resistance against E. coli,” said Fischbach on Twitter, “There are improvements to make, but we think hCom2 (in its current form) is a good model system of the microbiome.”
Future Microbial Studies
The Stanford team hopes its synthetic microbiome model will allow researchers around the world to have a common foundation for future studies and provide them with the ability to create engineered microbiome-based therapies.
“We built this consortium for the broader research community,” said Fischbach in the press release. “We want to get this into as many hands as possible to have an impact on the field.”
While direct links to new clinical laboratory tests and microbiome therapies have not yet been established, research like the Stanford study demonstrates the increasing value of the human microbiome as a source of diagnostic information that can guide decisions on better ways to treat patients.
