Scientists Map 661 Gut Microbes Linked to Heart and Metabolic Health in 34,000 People

Cardiometabolic diseases, including cardiovascular disease and type 2 diabetes, are the leading causes of death in Western countries, and both poor diet and gut microbiome composition have been implicated in their development. Yet large-scale, multi-national studies systematically linking specific microbial species to health markers across diverse populations have been lacking—until now.

This study assembled and harmonized five of the largest gut metagenomic cohorts to date from the ZOE PREDICT programme, encompassing 34,694 participants from the United States and United Kingdom. Each participant provided stool samples for shotgun metagenomic sequencing alongside detailed dietary records, anthropometric measurements (including BMI), and a comprehensive panel of 37 clinical markers spanning glycemia, lipid profiles, inflammatory markers such as GlycA, blood pressure, and atherosclerotic cardiovascular disease (ASCVD) risk scores.

Using a systematic machine learning approach—including random forest classifiers and regression models trained on species-level relative abundances—the researchers found consistent, moderately strong associations between the microbiome and surrogate health markers across all five cohorts. Key predicted markers included fasting and postprandial glycemia, triglycerides, cholesterol, and inflammatory indices, with AUC values ranging from 0.64 to 0.73 and Spearman correlations of 0.30–0.46. Dietary quality indices such as the Healthy Eating Index and the Healthful Plant-Based Diet Index also correlated meaningfully with microbiome composition.

To distil actionable insight, the team computed partial Spearman's correlations (adjusted for sex, age, and BMI) between each of 661 prevalent microbial species and all 37 health markers, then averaged and ranked species across cohorts. This produced the 'ZOE Microbiome Health Ranking 2025,' a reproducible summary ranking microbes from most favourably to most unfavourably associated with host health. The majority of top-ranked species—both favourably and unfavourably—belonged to the Firmicutes phylum and Clostridia class, particularly the Lachnospiraceae family, highlighting that beneficial and harmful microbes can coexist within the same taxonomic group. The ranking was independently validated in over 7,800 publicly available metagenomic samples and showed strong associations with BMI and disease conditions in those external datasets.

Critically, in two separate dietary intervention clinical trials totalling 746 participants, adherence to healthier dietary patterns led to increases in the abundance and prevalence of favourably ranked species and reductions in unfavourably ranked ones—providing preliminary interventional support for the ranking's biological relevance. The authors emphasise, however, that these are observational associations and that establishing causality requires prospective cohort studies and rigorously designed interventional trials. The ZOE Microbiome Health Ranking 2025 is nonetheless positioned as a principled, large-scale foundation for guiding future mechanistic and causal research into gut microbiome-targeted dietary interventions for cardiometabolic health.