%0 Journal Article %A Klier, Kristin %A Mehrjerd, Ameneh %A Fässler, Daniel %A Franck, Maximilien %A Weihs, Antoine %A Budde, Kathrin %A Bahls, Martin %A Frost, Fabian %A Henning, Ann-Kristin %A Heinken, Almut %A Völzke, Henry %A Dörr, Marcus %A Nauck, Matthias %A Grabe, Hans Jörgen %A Friedrich, Nele %A Hertel, Johannes %T Integrating population-based metabolomics with computational microbiome modelling identifies methanol as a urinary biomarker for protective diet-microbiome-host interactions. %J Food & function %V 16 %N 18 %@ 2042-6496 %C Cambridge %I RSC %M DZNE-2025-01106 %P 7067 - 7081 %D 2025 %X 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 %K Humans %K Biomarkers: urine %K Methanol: urine %K Methanol: metabolism %K Metabolomics %K Male %K Gastrointestinal Microbiome: physiology %K Female %K Middle Aged %K Diet %K Adult %K Host Microbial Interactions %K Aged %K Biomarkers (NLM Chemicals) %K Methanol (NLM Chemicals) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:40856313 %R 10.1039/D5FO00761E %U https://pub.dzne.de/record/281359