Faecal metabolites as a readout of habitual diet capture dietary interactions with the gut microbiome
The interplay between diet and gut microbiome composition is complex. Faecal metabolites, the end products of human and microbial metabolism, provide insights into these interactions. Here, we integrate faecal metabolomics, metagenomics, and habitual dietary data from 1810 individuals from the TwinsUK and 837 from the ZOE PREDICT1 cohorts. Using machine learning models, we find that faecal metabolites accurately predict reported intakes of 20 food groups (area under the curve (AUC) > 0.80 for meat, nuts and seeds, wholegrains, tea and coffee, and alcohol) and adherence to seven dietary patterns (AUC from 0.71 for the Plant-based Diet Index to 0.83 for the Dietary Approaches to Stop Hypertension score). Notably, the faecal metabolome is a stronger predictor of atherosclerotic cardiovascular disease risk (AUC = 0.86) than the Dietary Approaches to Stop Hypertension score (AUC = 0.66). We identify 414 associations between 19 food groups and 211 metabolites, that significantly correlate with microbial α-diversity and 217 species. Our findings reveal that faecal metabolites capture mediations between diet and the gut microbiome, advancing our understanding of diet-related disease risk and informing metabolite-based interventions.
Authors
- Tim D. Spector (ORCID: https://orcid.org/0000-0002-9795-0365)
- Panayiotis Louca (ORCID: https://orcid.org/0000-0001-5956-1433)
- Mario Falchi (ORCID: https://orcid.org/0000-0002-5646-1004)
- Francesco Asnicar (ORCID: https://orcid.org/0000-0003-3732-1468)
- Kate Bermingham (ORCID: https://orcid.org/0000-0002-2530-1614)
- Xinyuan Zhang (ORCID: https://orcid.org/0000-0002-4636-1202)
- Jonathan Wolf (ORCID: https://orcid.org/0000-0002-0530-2257)
- Andrei-Florin Baleanu
- Rachel Gibson (ORCID: https://orcid.org/0000-0002-5823-6468)
- Sarah Berry (ORCID: https://orcid.org/0000-0002-5819-5109)
- Emily R. Leeming (ORCID: https://orcid.org/0000-0002-0531-4901)
- Alessia Visconti (ORCID: https://orcid.org/0000-0003-4144-2019)
- Gregory Michelotti (ORCID: https://orcid.org/0000-0002-3936-4675)
- Nicola Segata (ORCID: https://orcid.org/0000-0002-1583-5794)
- Cristina Menni (ORCID: https://orcid.org/0000-0001-9790-0571)
- Yu Lin (ORCID: https://orcid.org/0000-0003-4720-6260)
- Kari E. Wong
- Richard S. Pope (ORCID: https://orcid.org/0009-0009-2786-6924)
Institutions
- King's College London (GB)
- University of Milan (IT)
- University of Trento (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Triangle (US)
- ZOE (United Kingdom) (GB)
- Metabolon (United States) (US)
- University of Turin (IT)
- University of Newcastle Australia (AU)
- Newcastle University (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1038/s41467-025-66046-7
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Wellcome Trust
- Dipartimenti di Eccellenza
- National Institute for Health and Care Research
- King's College London
- European Commission
- Ministero della Salute
- Versus Arthritis
- Medical Research Council