Vegans have distinct profiles of their gut microbiome and multi-compartment metabolome that align with markers of metabolic health

Adherence to a vegan diet is associated with improved cardiometabolic health. Here, we relate the outcome of shotgun sequencing of faecal DNA, serum, faecal and urine metabolomics, and systemic cytokine profiling with measures of clinical and biochemical markers of cardiometabolic health in 75 vegans and 75 omnivores without known diseases. Compared with omnivorous, the diet of vegans was enriched in fibres and digestible carbohydrates and lower in protein and fat. Vegans displayed favourable cardiometabolic phenotypes including lower measures of glycaemia, atherogenic plasma lipids and systemic inflammation. Despite a lower alpha-diversity, the vegan gut bacteriome exhibited distinct signatures with an enrichment of bacterial taxa that associated directly with intake of dietary fibres, and which were positively linked to health-related cardiometabolic scores based on the ZOE Microbiome Ranking 2024. In addition, within vegans, measures of bacterial diversity correlated positively with dietary protein intake. Omnivore-enriched bacterial species that associated with favourable metabolic health outcomes according to the ZOE ranking were also enriched in those vegans who had a high-protein intake compared to vegans with a low-protein intake. Further, the vegan gut microbiome was featured by a lower abundance of virulent bacteriophages and viral auxiliary metabolic genes as well as a higher prevalence of the eukaryotic Blastocystis protist that associated with a lower systolic blood pressure. In omnivores, the abundance of several gut bacteriome-derived metabolites including trimethylamine-N-oxide and p -cresyl sulphate associated with markers of adverse metabolic and renal outcomes. We show how a vegan diet is associated with a coordinated restructuring of the gut bacteriome, virome, Blastocystis prevalence and the multi-component metabolome, findings that provide insights into potential mechanisms underlying the associations between diet and human cardiometabolic health. Video Abstract