Diets rich in certain plant-based foods are linked with the presence of gut microbes that are associated with a lower risk of developing disorders such as obesity, type 2 diabetes, and cardiovascular disease (CVD), according to recent results from a large-scale international study that included researchers from King’s College London, the Harvard T.H. Chan School of Public Health, Massachusetts General Hospital (MGH), the University of Trento, Italy, and health science start-up company ZOE.
Through what they claim is the most detailed study of its kind, the researchers applied metagenomics and blood chemical profiling techniques to uncover a panel of 15 gut microbes associated with lower risks (and 15 with higher risks) for a number of common diseases. Their findings included some novel microbes that have not yet even been named.
The investigators suggest that their results could be used to provide personalized dietary advice for better health, based on gut microbiome testing. “This study demonstrates a clear association between specific microbial species in the gut, certain foods, and risk of some common diseases,” said gastroenterologist Andrew T. Chan, who is chief of the clinical and translational epidemiology unit at Massachusetts General Hospital, and professor of medicine at Harvard Medical School. “We hope to be able to use this information to help people avoid serious health problems by changing their diet to personalize their gut microbiome.” Chan is co-senior author of the team’s published paper in Nature Medicine, which is titled, “Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals.”
Dietary contributions to health and chronic disorders, such as obesity, metabolic syndrome, cancer, and cardiovascular disease, are of “universal importance,” the authors noted. But while obesity and associated mortality/morbidity have risen dramatically over the past few decades, the team continued, and the gut microbiome has been implicated as one of several potentially causal human-environment interactions, “… the details of the microbiome’s role in obesity and cardiometabolic health have proven difficult to define reproducibly in large human populations ….”
To help address and overcome existing challenges associated with large-scale human studies, the international team launched the Personalized Responses to Dietary Composition Trial (PREDICT 1) study of diet-microbiome interactions in metabolic health, involving subjects in the United States and in the U.K. “PREDICT 1 included >1,000 participants profiled pre- and post-standardized dietary challenges using intensive in-clinic biometric and blood measures, habitual dietary data collection, continuous glucose monitoring, and stool metagenomics,” they explained in the Nature Medicine paper.
For the reported study the researchers carried out deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals in the PREDICT 1 trial, for whom detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements, were available. “Studying the interrelationship between the microbiome, diet, and disease involves a lot of variables because peoples’ diets tend to be personalized and may change quite a bit over time,” said Chan. “Two of the strengths of this trial are the number of participants and the detailed information we collected.”
The results of their analyses provided evidence that the subjects’ gut microbiome was strongly linked with specific nutrients, food groups, and dietary composition, and that, in turn, certain microbes in the gut are linked to biomarkers of metabolic disease. Surprisingly, the microbiome appears to have a greater association to these markers than other factors, such as genetics.
The overall findings indicated that participants who ate a diet rich in healthy, plant-based foods were more likely to have high levels of “good” gut microbes. Conversely, diets containing more highly processed plant-based foods were more likely to be associated with the “bad” gut microbes. The results identified robust microbiome-based biomarkers of obesity, as well as markers for cardiovascular disease and impaired glucose tolerance, which are key risk factors for COVID-19. The results more specifically revealed that having a microbiome rich in Prevotella copri and Blastocystis species was associated with maintaining a favorable blood sugar level after a meal. Other species were linked to lower post-meal levels of blood fats and markers of inflammation.
The trends uncovered were so consistent, the researchers believe that their microbiome data can be used to help determine the risk of cardiometabolic disease among people who do not yet have symptoms, and possibly to prescribe a personalized diet that is designed specifically to improve someone’s health. “The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease,” the team noted.
“We were surprised to see such large, clear groups of ‘good’ and ‘bad’ microbes emerging from our analysis,” stated Nicola Segata, PhD, professor and principal investigator of the computational metagenomics lab at the University of Trento, Italy, and coordinator of the analysis of the microbiome data in the study. “And it is intriguing to see that microbiologists know so little about many of these microbes that they are not even named yet.” As the authors noted, “… these new contributions of the gut microbiome to human dietary responses may help to explain some of the heterogeneity seen among previous population studies.”
Curtis Huttenhower, PhD, a co-senior author who co-directs the Harvard T.H. Chan Microbiome in Public Health Center, added, “Both diet and the gut microbiome are highly personalized. PREDICT is one of the first studies to begin unraveling this complex molecular web at scale. Segata added: “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.”
The authors further concluded, “Overall, this is the first study to identify a shared diet–metabolic health microbial signature, segregating favorable and unfavorable taxa with multiple measures of both dietary intake and cardiometabolic health. As a resource, these results will aid both in the utilization of the gut microbiome as a biomarker for cardiometabolic risk and in strategies for reshaping the microbiome to improve personalized dietary health.”
The PREDICT study program was started by epidemiologist Tim Spector, PhD, from King’s College London, who is scientific founder of ZOE. He said, “When you eat, you’re not just nourishing your body, you’re feeding the trillions of microbes that live inside your gut.” PREDICT 2 completed its primary investigations in 2020 with a further 1,000 U.S participants, and PREDICT 3 launched a few months ago.
As a co-founder of ZOE, Spector further commented, “I am very excited that we have been able to translate this cutting-edge science into an at-home test in the time it has taken for the research to be peer-reviewed and published. Through ZOE, we can now offer the public an opportunity to discover which of these microbes they have living in their gut. After taking ZOE’s at-home test, participants will receive personalized recommendations for what to eat, based on comparing their results with the thousands of participants in the PREDICT studies. By using machine learning, we can then share with you our calculations of how your body will respond to any food, in real-time through an app.”