Journal article
Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies
Gut, Vol.71(6), pp.1095-1105
06/14/2021
DOI: 10.1136/gutjnl-2021-324053
PMCID: PMC8697256
PMID: 34127525
Abstract
ObjectiveTryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.MethodWe analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.ResultsTryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals.ConclusionHigher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host–microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.
Details
- Title: Subtitle
- Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies
- Creators
- Qibin Qi - Harvard UniversityJun Li - Harvard UniversityBing Yu - The University of Texas Health Science Center at HoustonJee-Young Moon - Yeshiva UniversityJin C Chai - Yeshiva UniversityJordi Merino - Harvard UniversityJie Hu - Harvard UniversityMiguel Ruiz-Canela - Instituto de Salud Carlos IIICasey Rebholz - Johns Hopkins UniversityZheng Wang - Albert Einstein College of MedicineMykhaylo Usyk - Yeshiva UniversityGuo-Chong Chen - Yeshiva UniversityBianca C Porneala - Harvard UniversityWenshuang Wang - University of HoustonNgoc Quynh Nguyen - The University of Texas Health Science Center at HoustonElena V Feofanova - The University of Texas Health Science Center at HoustonMegan L Grove - The University of Texas Health Science Center at HoustonThomas J Wang - The University of Texas Southwestern Medical CenterRobert E Gerszten - Broad InstituteJosée Dupuis - Boston UniversityJordi Salas-Salvadó - Instituto de Salud Carlos IIIWei Bao - University of IowaDavid L Perkins - University of Illinois ChicagoMartha L Daviglus - University of Illinois ChicagoBharat Thyagarajan - University of Minnesota Medical CenterJianwen Cai - University of North Carolina at Chapel HillTao Wang - Yeshiva UniversityJoAnn E Manson - Harvard UniversityMiguel A Martínez-González - Instituto de Salud Carlos IIIElizabeth Selvin - Johns Hopkins UniversityKathryn M Rexrode - Harvard UniversityClary B Clish - Broad InstituteFrank B Hu - Harvard UniversityJames B Meigs - Harvard UniversityRob Knight - University of California San DiegoRobert D Burk - Yeshiva UniversityEric Boerwinkle - The University of Texas Health Science Center at HoustonRobert C Kaplan - Cancer Consortium
- Resource Type
- Journal article
- Publication Details
- Gut, Vol.71(6), pp.1095-1105
- DOI
- 10.1136/gutjnl-2021-324053
- PMID
- 34127525
- PMCID
- PMC8697256
- NLM abbreviation
- Gut
- ISSN
- 0017-5749
- eISSN
- 1468-3288
- Grant note
- DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: R01-DK119268
- Language
- English
- Date published
- 06/14/2021
- Academic Unit
- Epidemiology
- Record Identifier
- 9984363568402771
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