Role of maternal tryptophan metabolism in allergic diseases in the offspring

Role of maternal tryptophan metabolism in allergic diseases in the offspring

Clinical & Experimental Allergy

10.1111/cea.13953

http://dx.doi.org/10.1111/cea.13953

Hui Xing Lau, Sarah El‐Heis, Qai Ven Yap, Yiong Huak Chan, Cheryl Pei Ting Tan, Neerja Karnani, Karen Mei Ling Tan, Elizabeth Huiwen Tham, Anne Eng Neo Goh, Oon Hoe Teoh, Kok Hian Tan, Johan Gunnar Eriksson, Yap Seng Chong, Mary Foong‐Fong Chong, Hugo Van Bever, Bee Wah Lee, Lynette P. Shek, Keith M. Godfrey, Evelyn Xiu Ling Loo

Eczema, kynurenine pathway, Nicotinamide, tryptophan metabolism, vitamin B3

25 May 2021

Lau, H. X., El‐Heis, S., Yap, Q. V., Chan, Y. H., Tan, C. P. T., Karnani, N., Tan, K. M. L., Tham, E. H., Goh, A. E. N., Teoh, O. H., Tan, K. H., Eriksson, J. G., Chong, Y. S., Chong, M. F., Van Bever, H., Lee, B. W., Shek, L. P., Godfrey, K. M., & Loo, E. X. L. (2021). Role of maternal tryptophan metabolism in allergic diseases in the offspring. Clinical & Experimental Allergy, 51(10), 1346–1360. Portico. https://doi.org/10.1111/cea.13953

Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development.ObjectiveWe examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization.MethodsIn 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 of gestation and allergic outcomes collected through interviewer‐administered questionnaires at multiple time‐points 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.ResultsTryptophan 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 by 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 sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze.Conclusions and Clinical RelevanceMaternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.

Publisher Copyright

This research / project is supported by the National Medical Research Council - Translational and Clinical Research (TCR) Flagship Program
Grant Reference no. : NMRC/TCR/004-NUS/2008

This research / project is supported by the National Medical Research Council - Translational and Clinical Research (TCR) Flagship Program
Grant Reference no. : NMRC/TCR/012-NUHS/2014

This research is supported by core funding from: Singapore Institute for Clinical Sciences
Grant Reference no. : NA

This research / project is supported by the National Institute for Health Research - NIHR Southampton Biomedical Research Centre
Grant Reference no. : NA

This research / project is supported by the European Union - Seventh Framework Program
Grant Reference no. : FP7/2007–2013

This research / project is supported by the EarlyNutrition and ODIN - NA
Grant Reference no. : 289346

This research / project is supported by the EarlyNutrition and ODIN - NA
Grant Reference no. : 613977

This is the peer reviewed version of the following article: Lau, H. X., El‐Heis, S., Yap, Q. V., Chan, Y. H., Tan, C. P. T., Karnani, N., Tan, K. M. L., Tham, E. H., Goh, A. E. N., Teoh, O. H., Tan, K. H., Eriksson, J. G., Chong, Y. S., Chong, M. F., Van Bever, H., Lee, B. W., Shek, L. P., Godfrey, K. M., & Loo, E. X. L. (2021). Role of maternal tryptophan metabolism in allergic diseases in the offspring. Clinical &Experimental Allergy, 51(10), 1346–1360. Portico., which has been published in final form at https://doi.org/10.1111/cea.13953. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited

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