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.
“We were surprised to see such large, clear groups of what we informally call ‘good’ and ‘bad’ microbes emerging from our analysis,” Nicola Segata, PhD (above), told News Medical. Segata is a professor and principal investigator at the Computational Metagenomics Lab at the University of Trento in Italy, and co-author of the study. “It is also exciting to see that microbiologists know so little about many of these microbes that they are not even named yet. This is now a big area of focus for us, as we believe they may open new insights in the future into how we could use the gut microbiome as a modifiable target to improve human metabolism and health,” he added. Pathologists and clinical laboratory scientists who read Dark Daily are already familiar with the plethora of ways the human microbiome is being studied for use in diagnostic testing and drug therapy. (Photo copyright: University of Trento.)
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.
Although there are healthcare providers who see the potential in microbiome testing, many clinical laboratories are not yet ready to embrace microbiome-based testing
In an unlikely string of events, no less than Nordstrom, the national department store chain, announced in September that it would offer microbiome-based test claimed to “check gut health.” Apparently, its customers were interested in this clinical laboratory test, as the Nordstrom website currently indicates that the “Health Intelligence Test Kit by Viome” is already sold out!
What does it say about consumer interest in clinical laboratory self-testing that Nordstrom has decided to offer at-home microbiome tests to its store customers? Can it be assumed that Nordstrom conducted enough marketing surveys of its customers to determine: a) that they were interested in microbiome testing; and b) they would buy enough microbiome tests that Nordstrom would benefit financially from either the mark-up on the tests or from the derived goodwill for meeting customer expectations?
Whatever the motivation, the retail giant recently announced it had partnered with Viome Life Sciences to sell Viome’s microbiome testing kits to its customers online, and in 2022, at some Nordstrom retail locations. These tests are centered around helping consumers understand the relationship between their microbiome and nutrition.
Pathologists and clinical laboratories will want to track Nordstrom’s success or failure in selling microbiome-based assays to its consumers. Microbiomics is in its infancy and remains a very unsettled area of diagnostics. Similarly, Viome, a self-described precision health and wellness company that conducts mRNA analysis at scale, will need to demonstrate that its strategy of developing precision medicine diagnostics and therapeutics based on the human microbiome has clinical relevance.
Helping Consumers with ‘Precision Nutrition’
In a September news release, Viome founder and CEO Naveen Jain, a serial entrepreneur, said, “Both Viome and Nordstrom believe that true health and beauty start from within. There is no such thing as a universal healthy food or healthy supplement. What is right for one person can be wrong for someone else, especially when it comes to nutrition which is key to human longevity and vitality. Precision nutrition is the future!”
“Precision medicine seeks to improve the personalized treatment of diseases, and precision nutrition is specific to dietary intake. Both develop interventions to prevent or treat chronic diseases based on a person’s unique characteristics like DNA, race, gender, health history, and lifestyle habits. Both aim to provide safer and more effective ways to prevent and treat disease by providing more accurate and targeted strategies.
“Precision nutrition assumes that each person may have a different response to specific foods and nutrients, so that the best diet for one individual may look very different than the best diet for another.
“Precision nutrition also considers the microbiome, trillions of bacteria in our bodies that play a key role in various daily internal operations. What types and how much bacteria we have are unique to each individual. Our diets can determine which types of bacteria live in our digestive tracts, and according to precision nutrition the reverse is also true: the types of bacteria we house might determine how we break down certain foods and what types of foods are most beneficial for our bodies.”
Medical Laboratory Testing, not Guessing
Viome Life Sciences is a microbiome and RNA analysis company based in Bellevue, Wash. The test kit that Nordstrom is selling is called the Health Intelligence Test. It is an at-home mRNA test that can provide users with some insights regarding their health. Consumers use the kit to collect blood and fecal samples, then return those samples to Viome for testing.
In a press release announcing its collaboration with Nordstrom, Viome said, “In a world overwhelmed by information relating to diet and supplement advice, Viome believes in testing, not guessing and empowering its users with actionable insights. To date, Viome has helped over 250,000 individuals improve their health through precision nutrition powered by microbial and human gene expression insights.”
Nordstrom began offering Viome’s Health Intelligence Test kit for $199 on its website starting in September. As of this writing and noted above, the kits are sold out. Nordstrom plans to stock the kit in select stores starting in 2022.
Viome’s Health Intelligence Test kit (above) looks at the microbiome to determine gut health, cellular health, healthy aging, immune health, and stress responses. Test results offer consumers personalized nutritional suggestions and recommendations for supplements, probiotics, and prebiotics based on an individual’s biology. Test are performed by Viome’s own clinical laboratories and results sent directly to Nordstrom’s customers. (Photo copyright: Viome Life Sciences.)
Individuals who purchase the test submit blood and stool samples to Viome’s lab which performs an analysis of gene activity patterns in the user’s cells and microbiome. Viome provides the results to consumers within two to three weeks.
“This partnership is a giant step towards making our technology more accessible, so people can understand what’s right for their unique body,” Jain said in the news release. “We are inspired each day by the incredible changes our customers are seeing in their health including improvements in digestion, weight, stress, ability to focus, and more.”
According to the news release, Viome conducted blind studies earlier this year that revealed significant successes based on their precision nutritional approach to wellness. Study participants, Viome claims, improved their outcomes to four diseases through nutrition:
Is Microbiome Diagnostics Testing Ready for Clinical Use?
Microbiomics is a relatively new field of diagnostics research. Much more research and testing will be needed to prove its clinical value and efficacy in healthcare diagnostics. Nevertheless, companies are offering microbiomics testing to consumers and that has some healthcare providers concerned.
In the GeekWire article, David Suskind, MD, a gastroenterologist at Seattle Children’s Hospital and Professor of Pediatrics at the University of Washington, described Viome’s study methodology as “questionable,” adding, “I think this is a very interesting and exciting space and I do think there are definite potential implications, down the road. [However] we are not there in terms of looking at microbiome and making broad recommendation for individuals, as of yet.”
Will at-home clinical laboratory testing kits that analyze an individual’s microbiome someday provide data that help people lead healthier lives and ward off diseases? That’s Jain’s prediction.
In an article published in Well+Good, Jain said, “COVID-19 has, of course, been such a dark time, but one positive that did come from it is that more people are taking control of their own health. I really believe that the future of healthcare will be delivered not at the hospital, but at home.”
If this collaboration between Nordstrom and Viome proves successful, similar partnerships between at-home diagnostics developers and established retail chains may become even more common. And that should be on the radars of pathologists and clinical laboratories.
These new findings may affect how microbiology labs and physicians diagnose and treat several gastrointestinal conditions
Once again, a research effort has teased out new insights into the role the human microbiome plays in our digestive processes. Microbiologist and medical laboratory managers will be interested to learn that, according to the study team, specific microbes have a role in regulating how fast food moves through the digestive tract.
Researchers at the Dey Laboratory in Seattle recently examined the function of microbial bile acid metabolism in gut motility. They determined that “metabolites generated by the gut microbiome regulate gut transit,” according to a new paper published by the Fred Hutchinson Cancer Research Center (Fred Hutch).
“These findings have potential implications for the treatment of gastrointestinal conditions,” noted a Fred Hutch news release. This may mean new clinical laboratory tests to identify these strains of bacteria, along with new therapies for treating patients.
Gut motility (aka, Peristalsis) is the term used to describe the movement of food from the time it enters via the mouth until it leaves the body. This movement, the researchers found, is regulated by interactions between diet, the enteric nervous system (ENS) and the gut microbiota via processes that include bile acid metabolism.
Sex, Diet, and Lifestyle All Affect Treatment for Gastrointestinal Diseases
The Dey Laboratory researchers also discovered that sex was a significant variable in determining transit times with males having larger pro-motility effects.
“Our results suggest that strategies for treating or preventing gastrointestinal diseases may need to be tailored to sex and to biogeography of the gut,” they wrote. “While targeting the microbiome and the ENS is justified, our observation of significant transcriptional responses to defined interventions in a highly controlled gnotobiotic setting also highlights challenges to clinical translation.”
The researchers concluded that:
Gut microbiome-generated bile acids regulate colonic transit via TGR5 protein.
Lithocholic acid (LCA) had the largest colonic pro-motility effect.
Bile acids exert sex-biased effects on gut transit times.
Enteric nervous system (ENS) transcriptional responses are regional- and microbiome-specific.
“The human experience—which reflects the aggregate effects of the innumerable dietary ingredients that we consume daily, the hugely diverse metabolically dynamic microbes that inhabit our guts, our own digestive processes, and the interactions of all of the above that result in thousands of gut metabolites—entails significantly more complex and variable transcriptional responses to environmental cues,” the Dey Laboratory scientists concluded.
To perform their research, the scientists developed both high and low BSH (bile salt hydrolase) bacterial communities for germ-free mice, which are known to exhibit slower gut motility and less complex bile acid profiles than colonized animals. (See graphic above taken from the Dey Laboratory published paper.)
The spice turmeric and dyes were added to the diets of the mice to track gut motility. The mice that were given the BSH-high microbiota had higher fecal concentrations of unconjugated bile acids than those given the BSH-low form of the microbiota. The mice given the BSH-high version also experienced faster transit times, according to the researchers’ iScience paper.
The researchers also concluded that the BSH-high group had greater fecal concentrations of lithocholic acid (LCA) which indicates variations in bile acid metabolism might affect gut transit.
When the scientists infused bile acids directly into mouse colons, variable acids reacted differently with LCA having the fastest transit times. The researchers hypothesized that LCA might signal through a bile receptor known as TGR5 which blocked the effects of LCA on colonic transit times. TGR5, also called G protein-coupled bile acid receptor, functions as a cell surface receptor for bile acids.
The Dey Laboratory team developed a method to measure expression changes in ENS genes and found that neither BSH activity nor gut transit phenotypes were major drivers of gene expression changes. They found that the location of the gut segment, or biogeography, was the leading contributor to ENS signature variance between samples.
“We expected to see shared host transcriptional responses in mice harboring communities with similar metabolic profiles. However, we did not see this for the most part,” explained gastroenterologist Neelendu Dey, MD (above), a physician/scientist and Assistant Professor, Clinical Research Division, at Fred Hutchinson Cancer Research Center, in the press release. “If anything, shared responses were regional, and these signatures did not cluster by BSH/motility phenotypes.” (Photo copyright: Seattle Cancer Care Alliance.)
The scientists “identified consortium-specific transcriptional changes in genes involved in ENS signaling, development, maintenance, and bile acid metabolism, and these differed across regions of the GI tract. Together these findings indicate that ENS transcriptional responses are regional and microbiome-specific,” according to the Fred Hutch press release.
“This remains a confusing part of the story for us—how is it that we can see predictable host motility responses when colonizing the guts of gnotobiotic mice with phenotypically defined communities, but the middle-man (the host enteric nervous system) appears to have such varied responses?” the Dey Laboratory researchers noted in the press release.
“It suggests that gut motility phenotypes that appear similar may in fact represent (when we look under the hood) diverse host physiologic phenotypes that we are just beginning to understand,” they added.
The results of this study could have potential implications for the precision medicine diagnosis and treatment of gastrointestinal illnesses.
Blue Poop Challenge
Earlier this year, people were encouraged to participate in the “blue poop challenge” conducted by research company ZOE Global Limited (ZOE) to determine how long it takes food to travel through the body.
For the Blue Poop Challenge, individuals are asked to eat blue muffins and then report on the company’s website as to how long it took for the blue dye to appear in their stools.
The purpose of this ongoing study is to reveal pertinent information about an individual’s gut health and microbiome.
Since 2010, Dark Daily has reported on dozens of research studies and innovative developments involving human microbiome and gut bacteria and their critical importance in the development of clinical laboratory testing, drug therapies, and precision medicine.
These studies’ findings could lead to improved immune system therapeutics and associated clinical laboratory tests.
“All of this suggests the potential in the future for clinical laboratories and microbiologists to do microbiome testing in support of clinical care,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
More research is needed in these areas. But gut bacteria and the human microbiome are an integral part of our health and wellbeing. It is worth keeping an eye on new developments in those fields of study.
Researchers found that early in life intestinal microorganisms “educate” the thymus to develop T cells; findings could lead to improved immune system therapeutics and associated clinical laboratory tests
The researchers published their findings in Nature. They used engineered mice as the test subjects and say the study could lead to a greater understanding of human conditions such as Type 1 and Type 2 diabetes and inflammatory bowel disease (IBD). In turn, this new knowledge could lead to new diagnostic tests for clinical laboratories.
“From the time we are born, our immune system is set up so that it can learn as much as it can to distinguish the good from the bad,” Matthew Bettini, PhD, Associate Professor of Pathology said in a University of Utah news release.
Does Gut Bacteria ‘Educate’ the Immune System?
The researchers were attempting to learn how the body develops T cells specific to intestinal microorganisms. T cells, they noted, are “educated” in the thymus, an organ in the upper chest that is key to the adaptive immune system.
“Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection,” they wrote in their study. “Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen, while limiting inflammatory anti-commensal responses.”
Matthew Bettini, PhD (left), Associate Professor of Pathology at the University of Utah, co-authored the study along with Gretchen Diehl, PhD (right), an immunologist at Sloan Kettering Institute. The team also included researchers from the Baylor College of Medicine in Houston and the Washington University School of Medicine in St. Louis. “Our studies make clear that there is a window in which gut microbiota have access to the immune education process. This opens up possibilities for designing therapeutics that can influence the trajectory of the immune system during this early time point,” Bettini said in the University of Utah news release. (Photo copyright: University of Utah/Sloan Kettering Institute.)
Findings Challenge Earlier Assumptions about Microbiota’s Influence on Immunity
The researchers began by seeding the intestines of mice with segmented filamentous bacteria (SFB), which they described as “one of the few commensal microorganisms for which a microorganism-specific T-cell receptor has been identified.” In addition, SFB-specific T cells can be tracked using a magnetic enrichment technique, they wrote in Nature.
They discovered that in young mice, microbial antigens from the intestines migrated to the thymus, resulting in an expansion of T cells specific to SFB. But they did not see an expansion of T cells in adult mice, suggesting that the process of adapting to microbiota happens early.
“Our study challenges previous assumptions that potential pathogens have no influence on immune cells that are developing in the thymus,” Bettini said in the news release. “Instead, we see that there is a window of opportunity for the thymus to learn from these bacteria. Even though these events that shape which T cells are present happen early in life, they can have a greater impact later in life.”
For example, T cells specific to microbiota can also protect against closely related harmful bacteria, the researchers found. “Mice populated with E. coli at a young age were more than six times as likely to survive a lethal dose of Salmonella later in life,” the news release noted. “The results suggest that building immunity to microbiota also builds protection against harmful bacteria the body has yet to encounter.”
According to the researchers, in addition to protecting against pathogens, “microbiota-specific T cells have pathogenic potential.” For example, “defects in these mechanisms could help explain why the immune system sometimes attacks good bacteria in the wrong place, causing the chronic inflammation that’s responsible for inflammatory bowel disease,” they suggested.
Other Clinical Laboratory Research into the Human Microbiome
All of this suggests the potential in the future “for clinical laboratories and microbiologists to do microbiome testing in support of clinical care,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report. Of course, more research is needed in these areas.
“We believe that our findings may be extended to areas of research where certain bacteria have been found to be either protective or pathogenic for other conditions, such as Type 1 and Type 2 diabetes,” Bettini said in the University of Utah news release. “Now we’re wondering, will this window of bacterial exposure and T cell development also be important in initiating these diseases?”
By analyzing ancient poop, researchers have discovered how much the human microbiome has changed over the past millennium, what may have brought about the change, and how those changes formed today’s human microbiome
Two thousand year-old human poop has yielded new insights into the evolution of the microbial cells (microbiota) inhabiting today’s human gut—collectively known as the human microbiome—that could help pathologists and clinical laboratories better understand diseases that may be linked to gut bacteria.
A recent study conducted by an international team of scientists reveals that the gut bacteria of today’s humans may have been altered by the onset of modern processed foods, sanitation, and the use of antibiotics.
In “Reconstruction of Ancient Microbial Genomes from the Human Gut,” published in the journal Nature, the researchers wrote, “In this study, we establish that palaeofaeces [Paleofeces in the US] with well-preserved DNA are abundant sources of microbial genomes, including previously undescribed microbial species, that may elucidate the evolutionary histories of human microbiomes. Similar future studies tapping into the richness of palaeofaeces will not only expand our knowledge of the human microbiome but may also lead to the development of approaches to restore present-day gut microbiomes to their ancestral state.”
Ancient Poop Is a ‘Time Machine’ into the Human Microbiome
To perform the research for this study, scientists analyzed Deoxyribonucleic acid (DNA) from eight preserved, fossilized feces (coprolites) to gain insight into the gut bacteria of ancient communities. The samples used in the research were originally found in rock formations in Utah and Mexico and were preserved by dryness and stable temperatures. The coprolites were between 1,000 and 2,000 years old.
“These paleofeces are the equivalent of a time machine,” Justin Sonnenburg, PhD, Associate Professor, Microbiology and Immunology at Stanford University and co-author of the study, told Science. Tiny bits of food found in the coprolites indicated that the diet of the ancient people included:
The dried-out poop samples were first radiocarbon dated. Then, tiny fragments of the coprolites were rehydrated which allowed researchers to recover longer DNA strands than those found in previous, similar studies. This study compared the microbiome of the ancient populations to that of present-day individuals. The authors of the study suggest that during the past millennium, the human microbiome has lost dozens of bacterial species and has become less diverse.
Other research studies have linked lower diversity among gut bacteria to higher rates of modern diseases, such as diabetes, obesity, and allergies, Science noted.
“We really wanted to be able to go back in time and see when those changes [in the modern gut microbiome] came about, and what’s causing them,” Archeological Geneticist Christina Warinner, PhD, Assistant Professor of Anthropology at Harvard University and one of the authors of the study, told Science. “Is it food itself? Is it processing, is it antibiotics, is it sanitation?” Warinner is the Sally Starling Seaver Assistant Professor at the Radcliffe Institute, and a group leader in the Department of Archaeogenetics at the Max Planck Institute for Evolutionary Anthropology and affiliated with the faculty of biological sciences at the Friedrich Schiller University in Jena, Germany. (Photo copyright: The Game Changers.)
Ancient versus Modern Microbiome
The ancient microbiomes lacked markers for antibiotic resistance and included dozens of bacterial species that were previously unknown. According to the study, “a total of 181 of the 498 reconstructed microbial genomes were classified as gut derived and had extensive DNA damage, consistent with an ancient origin, and 39% of the ancient genomes offered evidence of being newly discovered species.”
The scientists also discovered that the gut bacteria of present-day people living in non-industrialized societies is more like that of the ancient people when compared to present-day humans living in industrialized societies. But there are still vast differences between the ancient and the modern microbiome.
For example, a bacteria known as Treponema is virtually unknown in the microbiome of current humans, even those living in non-industrialized societies. However, according to Kostic, “They’re present in every single one of the paleofeces, across all the geographic sites. That suggests it’s not purely diet that’s shaping things,” he told Science.
What Can Clinical Laboratories Learn from Ancient Poop?
The ancient poop study scientists hope that future research on coprolites from the past will reveal more information regarding when shifts in the microbiome occurred and what events or human activities prompted those changes.
Research on the human microbiome has been responsible for many discoveries that have greatly impacted clinical pathology and diagnostics development.
Microbiologists and other medical laboratory scientists may soon have more useful biomarkers that aid in earlier, more accurate detection of disease, as well as guiding physicians to select the most effective therapies for specific patients, a key component of Precision Medicine.
The findings of this study are another step forward in understanding the composition and functions of gut bacteria. The study of the microbiome could prove to be a growth area for clinical laboratories and microbiology labs as well. It is probable that soon, labs will be performing more microbiome testing to help with the diagnosis, and treatment selection and monitoring of patients.
