Author, as appears in the article.: Qi Q; Li J; Yu B; Moon JY; Chai JC; Merino J; Hu J; Ruiz-Canela M; Rebholz C; Wang Z; Usyk M; Chen GC; Porneala BC; Wang W; Nguyen NQ; Feofanova EV; Grove ML; Wang TJ; Gerszten RE; Dupuis J; Salas-Salvadó J; Bao W; Perkins DL; Daviglus ML; Thyagarajan B; Cai J; Wang T; Manson JAE; Martínez-González MA; Selvin E; Rexrode KM; Clish CB; Hu FB; Meigs JB; Knight R; Burk RD; Boerwinkle E; Kaplan RC
Department: Bioquímica i Biotecnologia
URV's Author/s: MERINO RIBAS, JORDI / Salas Salvadó, Jorge
Keywords: Genome-wide association Genetics Dietary factors Diabetes mellitus risk pathway kynurenine impact heart health design acid
Abstract: Objective: Tryptophan 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. Method: We 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. Results: Tryptophan, 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. Conclusion: Higher 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.
Thematic Areas: Medicina iii Medicina ii Medicina i General medicine Gastroenterology & hepatology Gastroenterology Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: jordi.salas@urv.cat
Author identifier: 0000-0003-2700-7459
Record's date: 2024-08-24
Papper version: info:eu-repo/semantics/submittedVersion
Link to the original source: https://gut.bmj.com/content/71/6/1095
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Gut. 71 (6): 1095-1105
APA: Qi Q; Li J; Yu B; Moon JY; Chai JC; Merino J; Hu J; Ruiz-Canela M; Rebholz C; Wang Z; Usyk M; Chen GC; Porneala BC; Wang W; Nguyen NQ; Feofanova EV; G (2022). 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, 71(6), 1095-1105. DOI: 10.1136/gutjnl-2021-324053
Article's DOI: 10.1136/gutjnl-2021-324053
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV