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.
The study ‘shows that measurement using a urine test provides improved accuracy relative to other measurement methods, for example certain kinds of blood tests,’ a KI news release states
Researchers at the Karolinska Institute (KI) in Sweden have developed a non-invasive urine-based test that can identify what type of asthma a patient has and its severity. If developed into a clinical laboratory diagnostic, such a test also could give clinicians a better idea of what treatment is more likely to be effective—a core goal of precision medicine.
Another benefit of this methodology is that it is a non-invasive test. Should further studies conclude that this urine-based test produces accurate results acceptable for clinical settings, medical laboratories would certainly be interested in offering this assay, particularly for use in pediatric patients who are uncomfortable with the venipunctures needed to collect blood specimens. Also, given the incidence of asthma in the United States, there is the potential for a urine-based asthma test to generate a substantial number of test requests.
The objective of the study, according to the Karolinska Institute researchers, was “To test if urinary eicosanoid metabolites can direct asthma phenotyping.” The team used mass spectrometry to measured certain lipid biomarkers (prostaglandins and leukotrienes), which are known to play a key role in the inflammation that occurs during asthma attacks.
According to a KI news release, “The study is based on data from the U-BIOPRED study (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes), which was designed to investigate severe asthma. The study included 400 participants with severe asthma, which often requires treatment with corticosteroid tablets, nearly 100 individuals with milder forms of asthma, and 100 healthy control participants.”
“We discovered particularly high levels of the metabolites of the mast cell mediator prostaglandin D2 and the eosinophil product leukotriene C4 in asthma patients with what is referred to as Type 2 inflammation. Using our methodology, we were able to measure these metabolites with high accuracy and link their levels to the severity and type of asthma,” said Johan Kolmert, PhD (above), a post-doctoral researcher at the Institute of Environmental Medicine, Karolina Institute, and first author of the study, in the KI news release. If perfected, such accuracy could lead to effective precision medicine clinical laboratory tests. (Photo copyright: Karolinska Institute.)
More Accurate Testing Could Lead to Biomarker-guided Precision Medicine
In the US alone, 25,131,132 people currently suffer from asthma, about five million of which are children under the age of 18, according to 2019 CDC statistics. The World Health Organization (WHO) reports that worldwide, “Asthma affected an estimated 262 million people in 2019 and caused 461,000 deaths.”
People with mild asthma may have good success using steroid inhalers. However, for those with moderate to severe asthma where inhalers are not effective, oral corticosteroids may also be necessary. But corticosteroids have been associated with high blood pressure and diabetes, among other negative side effects.
“To replace corticosteroid tablets, in recent times several biological medicines have been introduced to treat patients with Type 2 inflammation characterized by increased activation of mast cells and eosinophils,” said Sven-Erik Dahlén, Professor at the Institute of Environmental Medicine, Karolinska Institute, in the news release.
Currently, there are no simple tests that show what type of asthma a patient has. Instead, clinicians rely on lung function tests, patient interviews, allergy tests, and blood tests.
Earlier this year, researchers at Brigham and Women’s Hospital and Exosome Diagnostics in Massachusetts investigated a non-invasive, urine-based test for transplant rejection. According to a news release, “Patients can spend up to six years waiting for a kidney transplant. Even when they do receive a transplant, up to 20% of patients will experience rejection.”
“If rejection is not treated, it can lead to scarring and complete kidney failure. Because of these problems, recipients can face life-long challenges,” said Jamil Azzi, MD, Director of the Kidney Transplantation Fellowship Program at Brigham and Women’s Hospital, and Associate Professor of Medicine at Harvard School of Medicine. “Our goal is to develop better tools to monitor patients without performing unnecessary biopsies. We try to detect rejection early, so we can treat it before scarring develops,” he said.
Detecting Bladder Cancer with Urine Testing
Another condition where urine tests are being investigated is bladder cancer. An article in Trends in Urology and Men’s Health states, “Several point-of-care urine tests have been developed to help identify patients who may be at higher risk of bladder cancer.” Those tests could have the potential for use in primary care, which could mean fewer people would need invasive, painful, and risk-carrying cystoscopies.
“New tests to help identify hematuria patients who are at a higher risk of cancer would help to improve the diagnostic pathway, reduce the number diagnosed by emergency presentation, lessen the burden on urology services, and spare those who do not have cancer an invasive and costly examination, such as cystoscopy,” the article’s authors wrote.
These urine-based tests are still under investigation by various research teams and more research is needed before clinical trials can be conducted and the tests can be submitted for regulatory approval. Though still in the early stages of development, urine-based diagnostic testing represents far less invasive, and therefore safer, ways to identify and treat various diseases.
Studies into how the elements in urine might be used as biomarkers for clinical laboratory tests may lead to improved non-invasive precision medicine diagnostics that could save many lives.
