Person:

Nguyen, Long

Few studies have formally tested the interaction between diet and the gut microbiome in the context of cardiometabolic health, particularly with the microbiome considered as a potential mediator rather than a target of dietary effects. Here, we investigated 307 male participants in the Health Professionals Follow-Up Study who provided up to four stool samples each, yielding 925 shotgun metagenomes and 340 metatranscriptomes, long-term dietary information, and biomarkers of glucose homeostasis, lipid metabolism, and inflammation from blood samples. We demonstrate that a healthy Mediterranean-style dietary pattern is associated with functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary, depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings represent a step forward in the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.

The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. 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.