Maternal and neonatal metabolomes and their associations to immune maturation and allergy in early life
Doctoral thesis, 2022
Allergy, one of the most common chronic diseases worldwide, is caused by a dysregulated immune system reacting to normally harmless proteins. However, regulating mechanisms are not well understood. The aim of this thesis was to investigate if plasma and placenta metabolites associate prospectively to allergy development and immune maturation. The aim was further to explore differences between arterial and venous umbilical cord blood metabolomes, and if they associated with maternal or infant traits.
Placentas and plasma (maternal from pregnancy and delivery and from the umbilical cord) were obtained from the prospective NICE-cohort. Metabolites were measured by LC-MS and GC-MS.
None of the measured metabolomes associated with any of the investigated allergic outcomes (asthma, food allergy and eczema). Modest associations were observed between immune maturation (in particular memory B cells) and plasma and placenta metabolomes. Energy-related metabolites were higher in arterial cord blood, while amino acids were higher in venous cord blood. Amino acid and energy metabolites were higher in first born children compared to children with older siblings.
Overall, the results suggest that immunomodulatory metabolites might be transferred from mother to child during pregnancy, affecting the future production and maturation of immune cells. Studies involving umbilical cord should consider the differences in arterial and venous cord blood and the association of maternal parity in experimental design and data analysis.
Furthermore, algorithms for real-time quality monitoring in untargeted LC-MS metabolomics were developed to improve quality during data generation. Quality monitoring was based on general metrics (e.g. total intensity and number of peaks) and peak metrics from so-called landmark features (e.g. peak area and noise). Landmark features were discovered, validated and then extracted and used in procedures to automatically discover injections of poor data quality. The developed procedures show great promise for improved data generation in high-throughput metabolomics.
Placentas and plasma (maternal from pregnancy and delivery and from the umbilical cord) were obtained from the prospective NICE-cohort. Metabolites were measured by LC-MS and GC-MS.
None of the measured metabolomes associated with any of the investigated allergic outcomes (asthma, food allergy and eczema). Modest associations were observed between immune maturation (in particular memory B cells) and plasma and placenta metabolomes. Energy-related metabolites were higher in arterial cord blood, while amino acids were higher in venous cord blood. Amino acid and energy metabolites were higher in first born children compared to children with older siblings.
Overall, the results suggest that immunomodulatory metabolites might be transferred from mother to child during pregnancy, affecting the future production and maturation of immune cells. Studies involving umbilical cord should consider the differences in arterial and venous cord blood and the association of maternal parity in experimental design and data analysis.
Furthermore, algorithms for real-time quality monitoring in untargeted LC-MS metabolomics were developed to improve quality during data generation. Quality monitoring was based on general metrics (e.g. total intensity and number of peaks) and peak metrics from so-called landmark features (e.g. peak area and noise). Landmark features were discovered, validated and then extracted and used in procedures to automatically discover injections of poor data quality. The developed procedures show great promise for improved data generation in high-throughput metabolomics.
Untargeted Metabolomics
allergy
QC
quality control
plasma
umbilical cord
placenta
LC-MS
immune system
Author
Olle Hartvigsson
Chalmers, Biology and Biological Engineering, Food and Nutrition Science
Differences between Arterial and Venous Umbilical Cord Plasma Metabolome and Association with Parity
Metabolites,;Vol. 12(2022)
Journal article
Olle Hartvigsson, Malin Barman, Hardis Rabe, Anna Sandin, Agnes E. Wold, Carl Brunius, Ann-Sofie Sandberg. Associations of the placental metabolome with immune maturation up to one year of age in the Swedish NICE-cohort.
Associations of maternal and infant metabolomes with immune maturation and allergy development at 12 months in the Swedish NICE-cohort
Scientific Reports,;Vol. 11(2021)
Journal article
Olle Hartvigsson, Anton Ribbenstedt, Marina Armeni, Kristian Pirttilä, Rui Zheng, Otto Savolainen & Carl Brunius. Continuous Quality Monitoring for Non-target MS-based Analysis.
Allergi, en av världens vanligaste kroniska sjukdomar, orsakas av ett felreglerat immunsystem som reagerar på normalt ofarliga proteiner, men kunskap om underliggande mekanismer saknas. Placentor och blodplasma (från mammor under graviditet, förlossning och navelsträngar) erhölls från den svenska NICE-studien. Metaboliter i dessa uppmättes med LC-MS och GC-MS.
Inget av metabolomen (uppmätta metabolitprofiler) associerade med allergiutfall (astma, födoämnesallergi eller eksem). Måttliga samband observerades mellan immunmognad (särskilt minnes-B-celler) och metabolom från plasma och placenta. Energimetaboliter fanns i högre koncentration i navelsträngsblod från mamman till barnet (venöst), medan aminosyror var högre från barnet till mamman (arteriellt). Aminosyra- och energimetaboliter var högre hos förstfödda barn jämfört med icke-förstfödda. Sammantaget tyder resultaten på att immunpåverkande metaboliter kan överföras från mamma till barn under graviditeten, vilket påverkar framtida produktion och mognad av immunceller. Dessutom bör studier av navelsträngsblod ta hänsyn till skillnader mellan arteriellt och venöst navelsträngsblod samt om modern är förstföderska.
Dessutom utvecklades metoder för automatisk monitorering av instrumentkvalitet i realtid, för att adressera problemet med skiftande datakvalitet inom LC-MS-metabolomik. Utvecklade algoritmer visar lovande resultat för kvalitetskontroll, vilket förväntas ge förbättrad datakvalitet och resursutnyttjande.
Inget av metabolomen (uppmätta metabolitprofiler) associerade med allergiutfall (astma, födoämnesallergi eller eksem). Måttliga samband observerades mellan immunmognad (särskilt minnes-B-celler) och metabolom från plasma och placenta. Energimetaboliter fanns i högre koncentration i navelsträngsblod från mamman till barnet (venöst), medan aminosyror var högre från barnet till mamman (arteriellt). Aminosyra- och energimetaboliter var högre hos förstfödda barn jämfört med icke-förstfödda. Sammantaget tyder resultaten på att immunpåverkande metaboliter kan överföras från mamma till barn under graviditeten, vilket påverkar framtida produktion och mognad av immunceller. Dessutom bör studier av navelsträngsblod ta hänsyn till skillnader mellan arteriellt och venöst navelsträngsblod samt om modern är förstföderska.
Dessutom utvecklades metoder för automatisk monitorering av instrumentkvalitet i realtid, för att adressera problemet med skiftande datakvalitet inom LC-MS-metabolomik. Utvecklade algoritmer visar lovande resultat för kvalitetskontroll, vilket förväntas ge förbättrad datakvalitet och resursutnyttjande.
The role of prenatal diet- and microbiome- derived metabolome in childhood allergy development. Metabolic fingerprinting for allergy prediction
Swedish Research Council (VR) (2019-01317), 2020-01-01 -- 2023-12-31.
Infrastructure
Chalmers Infrastructure for Mass spectrometry
Subject Categories
Biological Sciences
Medical Biotechnology
Roots
Basic sciences
Areas of Advance
Health Engineering
Life Science Engineering (2010-2018)
ISBN
978-91-7905-713-8
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 5179
Publisher
Chalmers