With further research, clinical laboratories may soon be performing macrobiotic testing to measure certain bacterial levels in patients’ gut bacteria
New insights from the University of Chicago (UChicago) into how human microbiota (aka, gut bacteria) play a role in food allergies has the potential to change the way a number of gastrointestinal health conditions are diagnosed and treated. This would give microbiologists and clinical laboratories a greater role in helping physicians diagnose, treat, and monitor patients with these health issues.
Past research has shown that certain gut bacteria can prevent antigens that trigger allergic reactions from entering the bloodstream. For example, Clostridium bacteria in the stomach produce a short-chain fatty acid known as butyrate, a metabolite that promotes the growth of healthy bacteria in the gut. This helps keep the microbiome in balance.
One way butyrate is created in the gut is through the fermentation of fiber. However, a lack of fiber in the diet can deplete the production of butyrate and cause the microbiome to be out of balance. When this happens, a state known as dysbiosis occurs that disrupts the microbiome and can lead to food allergies.
Without butyrate, the gut lining can become permeable and allow food to leak out of the gastrointestinal tract and into the body’s circulatory system. This reaction can trigger a potentially fatal anaphylactic response in the form of a food allergy. Thus, eating enough fiber is critical to the production of butyrate and to maintaining a balanced microbiome.
But today’s western diet can be dangerously low in soluble fiber. Therefore, the scientists at the University of Chicago have developed “a special type of polymeric molecule to deliver a crucial metabolite produced by these bacteria directly to the gut, where it helps restore the intestinal lining and allows the beneficial bacteria to flourish. … these polymers, called micelles, can be designed to release a payload of butyrate, a molecule that is known to help prevent food allergies, directly in the small and large intestines,” according to a UChicago news release.
This will be of interest to microbiologists, in particular. It’s another example of researchers connecting a specific species of bacteria in the human microbiome to a specific benefit.
“It’s very unlikely that butyrate is the only relevant metabolite, but the beauty of this platform is that we can make polymers with other microbial metabolites that could be administered in conjunction with butyrate or other therapies,” said Cathryn Nagler, PhD (above), Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at UChicago and a senior author of the study. “So, the potential for the polymer platform is pretty much wide open.” As further research validates these findings, clinical labs are likely to be doing microbiomic testing to monitor these therapies. (Photo copyright: University of Chicago.)
Restoring Butyrate in the Gut
One way to treat this anomaly has been through a microbiota transplant—also called a fecal biota transplant—where the administration of a solution of fecal matter is transplanted from a donor into the intestinal tract of the recipient. This transplant alters the recipient’s gut microbial composition to a healthier state, but it has had mixed results.
So, the UChicago researchers went in another direction (literally). They created an oral solution of butyrate and administered it to mice in the lab. The purpose of the solution was to thwart an allergic reaction when the mice were exposed to peanuts.
But there was a problem with their oral solution. It was repulsive.
The researchers developed a new configuration of polymers that masked the butyrate. They then delivered these polymer micelles directly into the digestive systems of mice that lacked healthy gut bacteria or a proper gut linings.
The treatment restored the microbiome by increasing the production of peptides that obliterate harmful bacteria. This allowed more of the beneficial butyrate-producing bacteria to emerge, which protected the mice from an anaphylactic reaction to peanuts and even reduced the symptom severity in an ulcerative colitis model.
“We were delighted to see that our drug both replenished the levels of butyrate present in the gut and helped the population of butyrate-producing bacteria to expand,” said Cathryn Nagler, PhD, Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at the University of Chicago and a senior author of the study, in the press release. “That will likely have implications not only for food allergy and inflammatory bowel disease (IBD), but also for the whole set of non-communicable chronic diseases that have been rising over the last 30 years, in response to lifestyle changes and overuse of antibiotics in our society.”
Future Benefits of UChicago Treatment
According to data from the Asthma and Allergy Foundation of America, about 20 million Americans suffered from food allergies in 2021. This includes approximately 16 million (6.2%) of adults and four million (5.8%) of children. The most common allergens for adults are shellfish, peanuts, and tree nuts, while the most common allergens for children are milk, eggs, and peanuts.
The best way to prevent an allergic reaction to a trigger food is strict avoidance. But this can be difficult to ensure outside of the home. Therefore, scientists are searching for ways to prevent food allergies from happening in the first place. The micelle technology could be adapted to deliver other metabolites and molecules which may make it a potential platform for treating allergies as well as other inflammatory gastrointestinal diseases.
“It’s a very flexible chemistry that allows us to target different parts of the gut,” said Jeffrey Hubbell, PhD, Eugene Bell Professor in Tissue Engineering and Vice Dean and Executive Officer at UChicago’s Pritzker School of Molecular Engineering and one of the project’s principal investigators, in the UChicago news release. “And because we’re delivering a metabolite like butyrate, it’s antigen-agnostic. It’s one agent for many different allergic indications, such as peanut or milk allergies. Once we begin working on clinical trials, that will be a huge benefit.”
Nagler and Hubbell have co-founded a company called ClostraBio to further the development of butyrate micelles into a commercially available treatment for peanut and other food allergies. They hope to begin clinical trials within the next 18 months and expand the technology to other applications as well.
Further research and clinical trials are needed to prove the validity of using polymer micelles in the treatment of diseases. But it is possible that clinical laboratories will be performing microbiomic testing in the future to help alleviate allergic reactions to food and other substances.
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.
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.
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.
One key finding of interest to clinical laboratory scientists is that this research study indicates that the human microbiome may more closely correlate with blood markers of metabolic disease than the genome of individuals
In the search for more sensitive diagnostic biomarkers (meaning the ability to detect disease with smaller samples and smaller quantities of the target biomarker), an international team of researchers has teased out a finding that a panel of multiple biomarkers in the human microbiome is more closely correlated with metabolic disease than genetic markers.
The team also discovered that the foods an individual ate had a more powerful impact on their microbiomes than their genes. The study participants included several sets of identical twins. The researchers found that identical twins shared only about 34% of the same gut microbes. People who were unrelated shared 30% of the same gut microbes.
This is a fascinating insight for pathologists and microbiologists involved in the study of the human microbiome for use in development of precision medicine clinical laboratory testing and drug therapies.
Microbiome Markers for Obesity, Heart Disease, and More
The study began in 2018, when an international team of researchers analyzed the gut microbiomes, diets, and blood biomarkers for cardiometabolic health obtained from 1,100 mostly healthy adults in the United Kingdom (UK) and the United States (US). They collected blood samples from the participants before and after meals to examine blood sugar levels, hormones, cholesterol, and inflammation levels. Sleep and activity levels also were monitored. Participants had to wear a continuous glucose monitor for two weeks during the research period.
The scientists discovered that the composition of a healthy gut microbiome is strongly linked to certain foods, food groups, nutrients, and diet composition. They identified markers for obesity, impaired glucose tolerance, and cardiovascular disease in the gut bacteria.
“When you eat, you’re not just nourishing your body, you’re feeding the trillions of microbes that live inside your gut,” genetic epidemiologist Tim Spector, MD, FmedSCi, told Labroots. Spector is a professor of genetic epidemiology at King’s College London and one of the authors of the study.
The scientists found that a diet rich in nutrient-dense, whole foods was more beneficial to a healthy gut microbiome, which can be an indicator of good health. Individuals who ate minimally processed foods, such as vegetables, nuts, eggs, and seafood were more likely to have healthy gut bacteria than individuals who consumed large amounts of highly processed foods, like juices and other sweetened beverages, processed meats, and refined grains and foods that were high in added sugars and salt.
“It goes back to the age-old message of eating as many whole and unprocessed foods as possible,” Sarah Berry, PhD, a nutrition scientist at King’s College London and a co-author of the study told The New York Times. “What this research shows for the first time is the link between the quality of the food we’re eating, the quality of our microbiomes, and ultimately our health outcomes,” she added.
The researchers concluded that heavily processed foods tend to contain very minimal amounts of fiber, a macronutrient that helps promote good bacteria in the gut microbiome and leads to better metabolic and cardiovascular health.
They found that people who had healthy blood sugar levels following a meal had higher levels of good bacteria called Prevotella copri, a genus of gram-negative bacteria, and Blastocystis, a genus of single-celled heterokont parasites, present in their guts. These bacteria are associated with lower levels of visceral fat, which accumulates around internal organs and increases risk of heart disease.
These “good” microbes also are affiliated with lower levels of inflammation, better blood sugar control, and lower spikes in blood fat and cholesterol levels after meals.
The study also found that different people have wildly varying metabolic responses to the same foods, partially due to the types of bacteria residing in their gut microbiome. The consumption of some foods is better for overall health than other foods, but there is no definitive, one-size-fits-all diet that works for everyone.
“What we found in our study was that the same diet in two different individuals does not lead to the same microbiome, and it does not lead to the same metabolic response. There is a lot of variation,” Andrew Chan, MD, Professor of Medicine at Harvard Medical School, told The New York Times. Chan is also Chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital and co-author of the study.
Small Changes in Diet, Big Impact to Health
The team is now planning a clinical trial to test whether changes in diet can alter levels of good and bad microbes in the gut. If proven to be true, such information could help clinicians design personalized nutritional plans that would enable individuals to improve their gut microbiome and their overall health.
“As a nutritional scientist, finding novel microbes that are linked to specific foods, as well as metabolic health, is exciting,” Berry told News Medical. “Given the highly personalized composition of each individual’s microbiome, our research suggests that we may be able to modify our gut microbiome to optimize our health by choosing the best foods for our unique biology.
“We think there are lots of small changes that people can make that can have a big impact on their health that might be mediated through the microbiome,” Berry told The New York Times.
More research and clinical trials are needed before diagnostic tests that use microbiome biomarkers to detect metabolic diseases can be developed. But these early research findings are a sign to pathologists and clinical laboratory managers that microbiome-based assays may come to play a more significant role in the early detection of several metabolic diseases.
CDC reports more than 93-million US adults are obese, and health issues related to obesity include heart disease, stroke, type 2 diabetes, and cancers
In recent years, the role of the human microbiome in weight loss or weight gain has been studied by different research groups. There is keen interest in this subject because of the high rates of obesity, and diagnostic companies know that development of a clinical laboratory test that could assess how an individual’s microbiome affects his/her weight would be a high-demand test.
This is true of a study published this year in Mayo Clinic Proceedings. Researchers at Mayo Clinic looked at obese patients who were in an active lifestyle intervention program designed to help them lose weight. It was determined that gut microbiota can have a role in both hindering weight loss and supporting weight loss.
Gut Microbiota More Complicated than Previously Thought
The Mayo researchers determined “an increased abundance of Phascolarctobacterium was associated with [successful weight loss]. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was associated with failure to [lose] body weight. A gut microbiota with increased capability for carbohydrate metabolism appears to be associated with decreased weight loss in overweight and obese patients undergoing a lifestyle intervention program.”
How do bacteria impede weight loss? Vandana Nehra, MD, Mayo Clinic Gastroenterologist and co-senior author of the study, explained in a news release.
“Gut bacteria have the capacity to break down complex food particles, which provides us with additional energy. And this is normally is good for us,” she says. “However, for some individuals trying to lose weight, this process may become a hindrance.”
Put another away: people who more effectively metabolized carbohydrates were the ones who struggled to drop the pounds, New Atlas pointed out.
Vandana Nehra, MD (left), and Purna Kashyap, MBBS (right), are Mayo Clinic Gastroenterologists and co-senior authors of the Mayo study. “While we need to replicate these findings in a bigger study, we now have an important direction to pursue in terms of potentially providing more individualized strategies for people who struggle with obesity,” Nehra noted in the news release. Thus, precision medicine therapy for obese individuals could be based on Mayo Clinic’s research. (Photo copyright: Mayo Clinic.)
Mayo Study Provides Clues to Microbiota Potential in Weight Loss
The Mayo researchers wanted to know how gut bacteria behave in people who are trying to lose weight.
They recruited 26 people, ranging in age from 18 to 65, from the Mayo Clinic Obesity Treatment Research Program. Fecal stool samples, for researchers’ analysis, were collected from participants at the start of the three-month study period and at the end. The definition of successful weight loss was at least 5% of body weight.
Nine people were successful, losing an average of 17.4 lbs.;
17 people did not meet the goal, losing on average just 3.3 lbs.; and,
More gut bacterial genes that break down carbohydrates were found in stool samples of the unsuccessful weight loss group, as compared to the successful dieters.
The researchers concluded that “An increased abundance of microbial genes encoding carbohydrate-active enzyme pathways and a decreased abundance of Phascolarctobacterium in the gut microbiota of obese and overweight individuals are associated with failure to lose at least 5% weight following a 3-month comprehensive lifestyle intervention program.”
Purna Kashyap, MBBS, Mayo Clinic Gastroenterologist and co-senior author of the study, told Live Science, “The study suggests there is a need to take the microbiome into account in clinical studies (on weight loss), and it also provides an important direction to pursue in terms of providing individualized care in obesity.” The very basis of precision medicine.
Future Weight-Loss Plans Based on Patient’s Microbiota
The Mayo Clinic researchers acknowledged the small sample size and need for more studies with larger samples over a longer time period. They also noted in their paper that Dialister has been associated with oral infections, such as gingivitis, and its role in energy expenditure and metabolism is unclear.
Still, the study suggests that it may soon be possible to give people individualized weight loss plans based on their gut bacteria. Clinical laboratory professionals and pathologists will want to stay abreast of follow-up studies and replication of findings by other research teams. A future medical laboratory test to analyze patients’ microbiomes could help obese people worldwide as well as lab business volume.