000281359 001__ 281359 000281359 005__ 20251008102405.0 000281359 0247_ $$2doi$$a10.1039/D5FO00761E 000281359 0247_ $$2pmid$$apmid:40856313 000281359 0247_ $$2ISSN$$a2042-6496 000281359 0247_ $$2ISSN$$a2042-650X 000281359 037__ $$aDZNE-2025-01106 000281359 041__ $$aEnglish 000281359 082__ $$a610 000281359 1001_ $$00009-0003-3098-5867$$aKlier, Kristin$$b0 000281359 245__ $$aIntegrating population-based metabolomics with computational microbiome modelling identifies methanol as a urinary biomarker for protective diet-microbiome-host interactions. 000281359 260__ $$aCambridge$$bRSC$$c2025 000281359 3367_ $$2DRIVER$$aarticle 000281359 3367_ $$2DataCite$$aOutput Types/Journal article 000281359 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1759835871_17321 000281359 3367_ $$2BibTeX$$aARTICLE 000281359 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000281359 3367_ $$00$$2EndNote$$aJournal Article 000281359 520__ $$aBackground: 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%) and Faecalibacterium (20.6%) being primarily responsible. Moreover, microbial methanol production capacity was a marker of high microbiome diversity. Finally, prospective survival analysis in SHIP-START-0 revealed that higher urinary methanol is associated with lower all-cause mortality in fully adjusted Cox regressions. Conclusion: Integrating population-based metabolomics and computational microbiome modelling identified urinary methanol as a promising biomarker for protective diet-microbiome interactions linked to microbial pectin degradation. 000281359 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000281359 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000281359 650_7 $$2NLM Chemicals$$aBiomarkers 000281359 650_7 $$0Y4S76JWI15$$2NLM Chemicals$$aMethanol 000281359 650_2 $$2MeSH$$aHumans 000281359 650_2 $$2MeSH$$aBiomarkers: urine 000281359 650_2 $$2MeSH$$aMethanol: urine 000281359 650_2 $$2MeSH$$aMethanol: metabolism 000281359 650_2 $$2MeSH$$aMetabolomics 000281359 650_2 $$2MeSH$$aMale 000281359 650_2 $$2MeSH$$aGastrointestinal Microbiome: physiology 000281359 650_2 $$2MeSH$$aFemale 000281359 650_2 $$2MeSH$$aMiddle Aged 000281359 650_2 $$2MeSH$$aDiet 000281359 650_2 $$2MeSH$$aAdult 000281359 650_2 $$2MeSH$$aHost Microbial Interactions 000281359 650_2 $$2MeSH$$aAged 000281359 7001_ $$aMehrjerd, Ameneh$$b1 000281359 7001_ $$aFässler, Daniel$$b2 000281359 7001_ $$aFranck, Maximilien$$b3 000281359 7001_ $$0P:(DE-2719)9002604$$aWeihs, Antoine$$b4$$udzne 000281359 7001_ $$aBudde, Kathrin$$b5 000281359 7001_ $$aBahls, Martin$$b6 000281359 7001_ $$aFrost, Fabian$$b7 000281359 7001_ $$aHenning, Ann-Kristin$$b8 000281359 7001_ $$aHeinken, Almut$$b9 000281359 7001_ $$aVölzke, Henry$$b10 000281359 7001_ $$aDörr, Marcus$$b11 000281359 7001_ $$aNauck, Matthias$$b12 000281359 7001_ $$0P:(DE-2719)2811781$$aGrabe, Hans Jörgen$$b13$$udzne 000281359 7001_ $$aFriedrich, Nele$$b14 000281359 7001_ $$aHertel, Johannes$$b15 000281359 773__ $$0PERI:(DE-600)2578152-2$$a10.1039/D5FO00761E$$gVol. 16, no. 18, p. 7067 - 7081$$n18$$p7067 - 7081$$tFood & function$$v16$$x2042-6496$$y2025 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106%20SUP1.pdf 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106%20SUP2.xlsx 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106.pdf$$yOpenAccess 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106%20SUP2.csv 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106%20SUP2.ods 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106%20SUP2.xls 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106%20SUP1.pdf?subformat=pdfa$$xpdfa 000281359 8564_ $$uhttps://pub.dzne.de/record/281359/files/DZNE-2025-01106.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000281359 909CO $$ooai:pub.dzne.de:281359$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000281359 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002604$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE 000281359 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811781$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE 000281359 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0 000281359 9141_ $$y2025 000281359 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-07 000281359 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-01-07 000281359 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000281359 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFOOD FUNCT : 2022$$d2025-01-07 000281359 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-01-07 000281359 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-01-07 000281359 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000281359 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bFOOD FUNCT : 2022$$d2025-01-07 000281359 915__ $$0StatID:(DE-HGF)0430$$2StatID$$aNational-Konsortium$$d2025-01-07$$wger 000281359 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-07 000281359 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-01-07 000281359 9201_ $$0I:(DE-2719)1510600$$kAG Hoffmann$$lTranslational Health Care Research$$x0 000281359 9201_ $$0I:(DE-2719)5000001$$kAG Grabe$$lBiomarkers of Dementia in the General Population$$x1 000281359 980__ $$ajournal 000281359 980__ $$aVDB 000281359 980__ $$aUNRESTRICTED 000281359 980__ $$aI:(DE-2719)1510600 000281359 980__ $$aI:(DE-2719)5000001 000281359 9801_ $$aFullTexts