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Role of maternal tryptophan metabolism in allergic diseases in the offspring

Role of maternal tryptophan metabolism in allergic diseases in the offspring
Role of maternal tryptophan metabolism in allergic diseases in the offspring
Background: nicotinamide (vitamin B3) is metabolite of tryptophan and a dietary precursor of enzymes involved in many regulatory processes, which may be influence fetal immune development.

Objective: we examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with risk of development of infant eczema, wheeze, rhinitis or allergic sensitization.

Methods: in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple timepoints and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured, and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method.

Results: tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis at 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitisation or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze.

Conclusions and Clinical Relevance: maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.
eczema, kynurenine pathway, nicotinamide, tryptophan metabolism, vitamin B3
0954-7894
1346-1360
Lau, Hui Xing
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El-Heis, Sarah
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Yap, Qai Ven
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Chan, Yiong Huak
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Tan, Cheryl Pei-Ting
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Karmani, Neerja
e1e6a7bb-c0d0-42ac-b740-429fa3895b43
Tan, Karen Mei Ling
f8c09297-2230-4125-80ca-409dbbe92d8e
Tham, Elizabeth Huiwen
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Goh, Anne Eng Neo
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Teoh, Oon Hoe
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Tan, Kok Hian
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Eriksson, Johan Gunnar
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Chong, Yap-Seng
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Chong, Mary F.F.
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van Bever, Hugo
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Lee, Bee Wah
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Shek, Lynette P.
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Godfrey, Keith
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Loo, Evelyn X.L.
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Lau, Hui Xing
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El-Heis, Sarah
6d7d2e03-3d63-4510-8b7e-fcbe4653db13
Yap, Qai Ven
ccb659a8-9154-46cd-8c86-57f3de54ff6e
Chan, Yiong Huak
6e604543-7616-48cc-a07e-86a80dfa5df0
Tan, Cheryl Pei-Ting
f7b59747-60ef-4616-9499-7c5397a282ec
Karmani, Neerja
e1e6a7bb-c0d0-42ac-b740-429fa3895b43
Tan, Karen Mei Ling
f8c09297-2230-4125-80ca-409dbbe92d8e
Tham, Elizabeth Huiwen
e22014ec-8242-478a-aafc-e4177164f814
Goh, Anne Eng Neo
9d869111-5368-420f-97dc-336f052bef41
Teoh, Oon Hoe
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Tan, Kok Hian
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Eriksson, Johan Gunnar
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Chong, Yap-Seng
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Chong, Mary F.F.
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van Bever, Hugo
967ee912-3ad6-4c7b-ab6c-bb50914ea687
Lee, Bee Wah
81ec0089-b824-4835-b908-1fc8e9f62249
Shek, Lynette P.
9a77403c-0e0c-4536-a5ad-628ce94b279a
Godfrey, Keith
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Loo, Evelyn X.L.
c21376cb-00e3-4c16-b6e4-1a81b66a7604

Lau, Hui Xing, El-Heis, Sarah, Yap, Qai Ven, Chan, Yiong Huak, Tan, Cheryl Pei-Ting, Karmani, Neerja, Tan, Karen Mei Ling, Tham, Elizabeth Huiwen, Goh, Anne Eng Neo, Teoh, Oon Hoe, Tan, Kok Hian, Eriksson, Johan Gunnar, Chong, Yap-Seng, Chong, Mary F.F., van Bever, Hugo, Lee, Bee Wah, Shek, Lynette P., Godfrey, Keith and Loo, Evelyn X.L. (2021) Role of maternal tryptophan metabolism in allergic diseases in the offspring. Clinical & Experimental Allergy, 51 (10), 1346-1360. (doi:10.1111/cea.13953). (In Press)

Record type: Article

Abstract

Background: nicotinamide (vitamin B3) is metabolite of tryptophan and a dietary precursor of enzymes involved in many regulatory processes, which may be influence fetal immune development.

Objective: we examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with risk of development of infant eczema, wheeze, rhinitis or allergic sensitization.

Methods: in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple timepoints and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured, and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method.

Results: tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis at 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitisation or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze.

Conclusions and Clinical Relevance: maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.

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Nicotinamide paper CEA submitted final clean 170521 - Accepted Manuscript
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Nicotinamide paper CEA final submitted supplementary tables 170521
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Nicotinamide Figure 1 vector 220421
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Nicotinamide graphical abstract 140521
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More information

Accepted/In Press date: 14 May 2021
Additional Information: Funding information: This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore—NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/ 2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. K.M Godfrey is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre and by the European Union's Seventh Framework Program (FP7/2007–2013), projects EarlyNutrition and ODIN under grant agreement numbers 289346 and 613977
Keywords: eczema, kynurenine pathway, nicotinamide, tryptophan metabolism, vitamin B3

Identifiers

Local EPrints ID: 449380
URI: http://eprints.soton.ac.uk/id/eprint/449380
ISSN: 0954-7894
PURE UUID: dc11e6a4-04d1-4197-a337-d3c263ecab24
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

Catalogue record

Date deposited: 26 May 2021 16:32
Last modified: 24 Nov 2021 02:33

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Contributors

Author: Hui Xing Lau
Author: Sarah El-Heis
Author: Qai Ven Yap
Author: Yiong Huak Chan
Author: Cheryl Pei-Ting Tan
Author: Neerja Karmani
Author: Karen Mei Ling Tan
Author: Elizabeth Huiwen Tham
Author: Anne Eng Neo Goh
Author: Oon Hoe Teoh
Author: Kok Hian Tan
Author: Johan Gunnar Eriksson
Author: Yap-Seng Chong
Author: Mary F.F. Chong
Author: Hugo van Bever
Author: Bee Wah Lee
Author: Lynette P. Shek
Author: Keith Godfrey ORCID iD
Author: Evelyn X.L. Loo

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