Do diet and microbes really ‘PREDICT’ cardiometabolic risks?
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Dietary habits are associated with the development of obesity and/or type 2 diabetes mellitus (T2DM), which are common risk factors for cardiovascular disease (CVD). Moreover, when diet is involved, the gut microbiota is complicit. Considerable interest has therefore focused on the role of human gut microbiota in health, CVD and metabolic disorders.

Accumulating evidence from in vivo experiments in rodents has revealed that intestinal microbiota has an important role in health and metabolic disorders; however, when it comes to humans, the role of the microbiota in (metabolic) diseases is unclear.

Contrary to studies using rodents, defining interrelationships between diet, the microbiome and disease in large-scale human studies has proved difficult and faces problems of reproducibility. Notably, human studies are burdened with many confounding factors that are continuous sources of variability, which make it difficult to disentangle cause and effect.

In an impressive effort to overcome these issues, researchers took nutritional investigation to the next level with their Personalized Responses to Dietary Composition Trial (PREDICT 1). This study aimed to quantify and predict individual variations in metabolic responses to standardized meals by deciphering diet–microbiome interactions in metabolic health.

The researchers used in-depth nutritional assessments with standardized dietary challenges over 14 days, intensive in-clinic biometric and blood measures, habitual dietary data collection, continuous glucose monitoring and stool shotgun metagenomics sequencing for taxonomic and functional profiling of the microbiota. More than 1,000 participants have been recruited, with a UK discovery cohort (n?=?1,002) and a validation population from the USA (n?=?100). The study also included 480 identical and non-identical twins.

Among the numerous results, the study confirms that genetics have only a minor role in determining an individual nutritional response and that this response is very personalized. In 56 of the 295 tested correlations, a statistically significant association was found between the structure of the microbiome and diet, personal characteristics and metabolic parameters. As previously observed in other human studies, microbiota species richness was inversely associated with BMI, visceral adipose tissue mass and predicted hepatic steatosis.

By contrast, species richness was positively correlated with cardiometabolic risk factors such as HDL cholesterol. In addition, PREDICT 1 also uncovered associations between microbiome richness and some emerging cardiometabolic biomarkers, including lipoprotein particle size and glycoprotein acetyl (an inflammatory biomarker).

A strength of this study is that, rather than focusing on single nutrients, different diets were divided into four categories, based on whether they are plant-based or animal-based and on whether they are considered ‘healthy’. A healthy diet was defined as one that contained a mix of foods associated with a decreased risk of chronic disease. The authors found tight correlations between microbial composition and the different categories of diet.

They also identified a panel of 15 gut microorganisms associated with decreased risks and 15 with increased risks for certain diseases, such as obesity and T2DM. Surprisingly, the strongest microbiome–habitual diet associations were driven by poorly characterized microorganisms, which strongly suggests that our knowledge of the bacteria — and their metabolic functions — that can contribute to health is still far from complete.