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

被引：167

作者：

Qi, Qibin ^{[1
,2
]}

Li, Jun ^{[2
,3
]}

Yu, Bing ^{[4
]}

Moon, Jee-Young ^{[1
]}

Chai, Jin C. ^{[1
]}

Merino, Jordi ^{[5
,6
]}

Hu, Je ^{[7
]}

Ruiz-Canela, Miguel ^{[8
,9
]}

Rebholz, Casey ^{[10
]}

Wang, Zheng ^{[1
]}

Usyk, Mykhaylo ^{[11
,12
,13
,14
]}

Chen, Guo-Chong ^{[1
]}

Porneala, Bianca C. ^{[15
]}

Wang, Wenshuang ^{[4
,16
]}

Nguyen, Ngoc Quynh ^{[4
]}

Feofanova, Elena, V ^{[4
]}

Grove, Megan L. ^{[4
]}

Wang, Thomas J. ^{[17
]}

Gerszten, Robert E. ^{[18
,19
,20
]}

Dupuis, Josee ^{[21
]}

Salas-Salvado, Jordi ^{[9
,22
]}

Bao, Wei ^{[23
]}

Perkins, David L. ^{[24
]}

Daviglus, Mariha L. ^{[24
]}

Thyagarijan, Bharat ^{[25
]}

Cai, Jianwen ^{[26
]}

Wang, Tao ^{[1
]}

Manson, JoAnn E. ^{[3
,27
]}

Martinez-Gonzalez, Miguel A. ^{[8
,9
]}

Selvin, Elizabeth ^{[10
]}

Rexrode, Kathryn M. ^{[7
]}

Clish, Clary B. ^{[28
]}

Hu, Frank B. ^{[29
]}

Meigs, James B. ^{[6
,15
]}

Knight, Rob ^{[30
,31
]}

Burk, Robert D. ^{[1
,11
,12
,13
,14
]}

Boerwinkle, Eric ^{[4
]}

Kaplan, Robert C. ^{[1
,32
]}

机构：

[1] Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[2] Harvard Univ TH Chan Sch Publ Hlth, Dept Nutrt, Boston, MA USA

[3] Harvard Univ TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[4] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA

[5] Massachusetts Gen Hosp, Diabet Unit, Ctr Genom Med, Boston, MA 02114 USA

[6] Harvard Med Sch, Dept Med, Boston, MA USA

[7] Harvard Med Sch, Dept Med, Div Womens Hlth, Brigham & Womens Hosp, Boston, MA USA

[8] Univ Navarra, Dept Prevent Med & Publ Hlth, Pamplona, Spain

[9] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid, Spain

[10] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA

[11] Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA

[12] Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[13] Yeshiva Univ Albert Einstein Coll Med, Dept Gynecol, Bronx, NY 10461 USA

[14] Yeshiva Univ Albert Einstein Coll Med, Dept Womens Hlth, Bronx, NY 10461 USA

[15] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA USA

[16] Univ Houston, Dept Math, Houston, TX 77204 USA

[17] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX USA

[18] Eli & Edythe L Broad Inst Harvard & MIT, Program Metab & Med, Cambridge, MA USA

[19] Eli & Edythe L Broad Inst Harvard & MIT, Program Populat Genet, Cambridge, MA USA

[20] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA USA

[21] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA

[22] Univ Rovira & Virgili, Fac Med & Hlth Sci, Human Nutr Unit, Dept Med & Cirurgia, Reus, Spain

[23] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA

[24] Univ Illinois, Inst Minor Hlth Res, Coll Med, Chicago, IL USA

[25] Univ Minnesota, Dept Lab Med & Pathol, Med Ctr, Minneapolis, MN USA

[26] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[27] Harvard Med Sch, Dept Med, Div Prevent Med, Brigham & Womens Hosp, Boston, MA USA

[28] Eli & Edythe L Broad Inst Harvard & MIT, Metabol Platform, Cambridge, MA USA

[29] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA

[30] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[31] Univ Calif San Diego, Dept Comp Sci & Engn, Ctr Microbiome Innovat, Jacobs Sch Engn, La Jolla, CA 92093 USA

[32] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

来源：

GUT | 2022年 / 71卷 / 06期

基金：

欧盟地平线“2020”;

关键词：

GENOME-WIDE ASSOCIATION; HEALTH; RISK; KYNURENINE; PATHWAY; DESIGN; IMPACT; HEART; ACID;

D O I：

10.1136/gutjnl-2021-324053

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：1095 / 1105

页数：11

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