TY - JOUR AU - Klier, Kristin AU - Mehrjerd, Ameneh AU - Fässler, Daniel AU - Franck, Maximilien AU - Weihs, Antoine AU - Budde, Kathrin AU - Bahls, Martin AU - Frost, Fabian AU - Henning, Ann-Kristin AU - Heinken, Almut AU - Völzke, Henry AU - Dörr, Marcus AU - Nauck, Matthias AU - Grabe, Hans Jörgen AU - Friedrich, Nele AU - Hertel, Johannes TI - Integrating population-based metabolomics with computational microbiome modelling identifies methanol as a urinary biomarker for protective diet-microbiome-host interactions. JO - Food & function VL - 16 IS - 18 SN - 2042-6496 CY - Cambridge PB - RSC M1 - DZNE-2025-01106 SP - 7067 - 7081 PY - 2025 AB - Background: Diet-microbiome interactions are core to human health, in particular through bacterial fibre degradation pathways. However, biomarkers reflective of these interactions are not well described. Methods: Using the population-based SHIP-START-0 cohort (n = 4017), we combined metabolome-wide screenings with elastic net machine learning models on 33 food items captured using a food frequency questionnaire (FFQ) and 43 targeted urine nuclear magnetic resonance (NMR) metabolites, identifying methanol as a marker of plant-derived food items. We utilised the independent SHIP-START-0 cohort for the replication of food-metabolite associations. Moreover, constraint-based microbiome community modelling using the Human Microbiome data (n = 149) was performed to predict and analyse the contribution of the microbiome to the human methanol pools through bacterial fibre degradation. Finally, we employed prospective survival analysis in the SHIP-START-0 cohort, testing urinary methanol on its predictive value for mortality. Results: Among 21 metabolites associated with 17 dietary FFQ variables after correction for multiple testing, urinary methanol emerged as the top hit for a range of plant-derived food items. In line with this, constraint-based community modelling demonstrated that gut microbiomes can produce methanol via pectin degradation with the genera Bacteroides (68.9 KW - Humans KW - Biomarkers: urine KW - Methanol: urine KW - Methanol: metabolism KW - Metabolomics KW - Male KW - Gastrointestinal Microbiome: physiology KW - Female KW - Middle Aged KW - Diet KW - Adult KW - Host Microbial Interactions KW - Aged KW - Biomarkers (NLM Chemicals) KW - Methanol (NLM Chemicals) LB - PUB:(DE-HGF)16 C6 - pmid:40856313 DO - DOI:10.1039/D5FO00761E UR - https://pub.dzne.de/record/281359 ER -