Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation

SysPharmPediA Consortium; Mahmoud I Abdel-Aziz; Simone Hashimoto; Anne H Neerincx; Eric G Haarman; Alexander Cecil; Jutta Lintelmann; Michael Witting; Stefanie M Hauck; Nikki Kerssemakers; Joris C Verster; Corinna Bang; Andre Franke; Barbara S Dierdorp; Tamara Dekker; Nariman K A Metwally; Jan Willem Duitman; René Lutter; Mario Gorenjak; Antoaneta A Toncheva; Parastoo Kheiroddin; Susanne Harner; Susanne Brandstetter; Christine Wolff; Paula Corcuera-Elosegui; Leyre López-Fernández; Javier Perez-Garcia; Mario Martin-Almeida; Olaia Sardón-Prado; Maria Pino-Yanes; Uroš Potočnik; Michael Kabesch; Susanne J H Vijverberg; Aletta D Kraneveld; Anke H Maitland-van der Zee

doi:10.1016/j.jaci.2025.04.017

Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation

SysPharmPediA Consortium, Mahmoud I Abdel-Aziz^*, Simone Hashimoto, Anne H Neerincx, Eric G Haarman, Alexander Cecil, Jutta Lintelmann, Michael Witting, Stefanie M Hauck, Nikki Kerssemakers, Joris C Verster, Corinna Bang, Andre Franke, Barbara S Dierdorp, Tamara Dekker, Nariman K A Metwally, Jan Willem Duitman, René Lutter, Mario Gorenjak, Antoaneta A TonchevaParastoo Kheiroddin, Susanne Harner, Susanne Brandstetter, Christine Wolff, Paula Corcuera-Elosegui, Leyre López-Fernández, Javier Perez-Garcia, Mario Martin-Almeida, Olaia Sardón-Prado, Maria Pino-Yanes, Uroš Potočnik, Michael Kabesch, Susanne J H Vijverberg, Aletta D Kraneveld, Anke H Maitland-van der Zee

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.

OBJECTIVE: We sought to identify phenotypes (metabotypes) in children with moderate to severe asthma through integrative fecal and serum metabolome analysis.

METHODS: Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step 3 or higher were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomic profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity network fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.

RESULTS: Integrative fecal and serum metabolome analysis of 92 children with moderate to severe asthma (median age, 11.5 years, 34% female) revealed 3 metabotypes. Metabotype 1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype 2 had higher odds of asthma control, the highest percentage of children with 4 or more months of breast-feeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and elevated serum acylcarnitines and ω-3 fatty acids. Metabotype 3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.

CONCLUSIONS: Metabotypes in children with moderate to severe asthma are linked to asthma control, distinct fecal microbiota, and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.

Original language	English
Journal	Journal of Allergy and Clinical Immunology
DOIs	https://doi.org/10.1016/j.jaci.2025.04.017
Publication status	E-pub ahead of print - 23 Apr 2025

Bibliographical note

Publisher Copyright:
© 2025 The Authors

Keywords

Moderate to severe childhood asthma
gut microbiota
inflammatory markers
metabotyping
precision medicine

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SysPharmPediA Consortium, Abdel-Aziz, M. I., Hashimoto, S., Neerincx, A. H., Haarman, E. G., Cecil, A., Lintelmann, J., Witting, M., Hauck, S. M., Kerssemakers, N., Verster, J. C., Bang, C., Franke, A., Dierdorp, B. S., Dekker, T., Metwally, N. K. A., Duitman, J. W., Lutter, R., Gorenjak, M., ... Maitland-van der Zee, A. H. (2025). Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation. Journal of Allergy and Clinical Immunology. Advance online publication. https://doi.org/10.1016/j.jaci.2025.04.017

@article{1910e4b0b521429dbd0d17320667c02d,

title = "Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation",

abstract = "BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.OBJECTIVE: We sought to identify phenotypes (metabotypes) in children with moderate to severe asthma through integrative fecal and serum metabolome analysis.METHODS: Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step 3 or higher were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomic profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity network fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.RESULTS: Integrative fecal and serum metabolome analysis of 92 children with moderate to severe asthma (median age, 11.5 years, 34% female) revealed 3 metabotypes. Metabotype 1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype 2 had higher odds of asthma control, the highest percentage of children with 4 or more months of breast-feeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and elevated serum acylcarnitines and ω-3 fatty acids. Metabotype 3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.CONCLUSIONS: Metabotypes in children with moderate to severe asthma are linked to asthma control, distinct fecal microbiota, and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.",

keywords = "Moderate to severe childhood asthma, gut microbiota, inflammatory markers, metabotyping, precision medicine",

author = "{SysPharmPediA Consortium} and Abdel-Aziz, {Mahmoud I} and Simone Hashimoto and Neerincx, {Anne H} and Haarman, {Eric G} and Alexander Cecil and Jutta Lintelmann and Michael Witting and Hauck, {Stefanie M} and Nikki Kerssemakers and Verster, {Joris C} and Corinna Bang and Andre Franke and Dierdorp, {Barbara S} and Tamara Dekker and Metwally, {Nariman K A} and Duitman, {Jan Willem} and Ren{\'e} Lutter and Mario Gorenjak and Toncheva, {Antoaneta A} and Parastoo Kheiroddin and Susanne Harner and Susanne Brandstetter and Christine Wolff and Paula Corcuera-Elosegui and Leyre L{\'o}pez-Fern{\'a}ndez and Javier Perez-Garcia and Mario Martin-Almeida and Olaia Sard{\'o}n-Prado and Maria Pino-Yanes and Uro{\v s} Poto{\v c}nik and Michael Kabesch and Vijverberg, {Susanne J H} and Kraneveld, {Aletta D} and {Maitland-van der Zee}, {Anke H}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = apr,

day = "23",

doi = "10.1016/j.jaci.2025.04.017",

language = "English",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

}

SysPharmPediA Consortium, Abdel-Aziz, MI, Hashimoto, S, Neerincx, AH, Haarman, EG, Cecil, A, Lintelmann, J, Witting, M, Hauck, SM, Kerssemakers, N, Verster, JC, Bang, C, Franke, A, Dierdorp, BS, Dekker, T, Metwally, NKA, Duitman, JW, Lutter, R, Gorenjak, M, Toncheva, AA, Kheiroddin, P, Harner, S, Brandstetter, S, Wolff, C, Corcuera-Elosegui, P, López-Fernández, L, Perez-Garcia, J, Martin-Almeida, M, Sardón-Prado, O, Pino-Yanes, M, Potočnik, U, Kabesch, M, Vijverberg, SJH, Kraneveld, AD & Maitland-van der Zee, AH 2025, 'Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2025.04.017

TY - JOUR

T1 - Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation

AU - SysPharmPediA Consortium

AU - Abdel-Aziz, Mahmoud I

AU - Hashimoto, Simone

AU - Neerincx, Anne H

AU - Haarman, Eric G

AU - Cecil, Alexander

AU - Lintelmann, Jutta

AU - Witting, Michael

AU - Hauck, Stefanie M

AU - Kerssemakers, Nikki

AU - Verster, Joris C

AU - Bang, Corinna

AU - Franke, Andre

AU - Dierdorp, Barbara S

AU - Dekker, Tamara

AU - Metwally, Nariman K A

AU - Duitman, Jan Willem

AU - Lutter, René

AU - Gorenjak, Mario

AU - Toncheva, Antoaneta A

AU - Kheiroddin, Parastoo

AU - Harner, Susanne

AU - Brandstetter, Susanne

AU - Wolff, Christine

AU - Corcuera-Elosegui, Paula

AU - López-Fernández, Leyre

AU - Perez-Garcia, Javier

AU - Martin-Almeida, Mario

AU - Sardón-Prado, Olaia

AU - Pino-Yanes, Maria

AU - Potočnik, Uroš

AU - Kabesch, Michael

AU - Vijverberg, Susanne J H

AU - Kraneveld, Aletta D

AU - Maitland-van der Zee, Anke H

PY - 2025/4/23

Y1 - 2025/4/23

N2 - BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.OBJECTIVE: We sought to identify phenotypes (metabotypes) in children with moderate to severe asthma through integrative fecal and serum metabolome analysis.METHODS: Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step 3 or higher were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomic profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity network fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.RESULTS: Integrative fecal and serum metabolome analysis of 92 children with moderate to severe asthma (median age, 11.5 years, 34% female) revealed 3 metabotypes. Metabotype 1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype 2 had higher odds of asthma control, the highest percentage of children with 4 or more months of breast-feeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and elevated serum acylcarnitines and ω-3 fatty acids. Metabotype 3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.CONCLUSIONS: Metabotypes in children with moderate to severe asthma are linked to asthma control, distinct fecal microbiota, and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.

AB - BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.OBJECTIVE: We sought to identify phenotypes (metabotypes) in children with moderate to severe asthma through integrative fecal and serum metabolome analysis.METHODS: Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step 3 or higher were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomic profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity network fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.RESULTS: Integrative fecal and serum metabolome analysis of 92 children with moderate to severe asthma (median age, 11.5 years, 34% female) revealed 3 metabotypes. Metabotype 1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype 2 had higher odds of asthma control, the highest percentage of children with 4 or more months of breast-feeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and elevated serum acylcarnitines and ω-3 fatty acids. Metabotype 3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.CONCLUSIONS: Metabotypes in children with moderate to severe asthma are linked to asthma control, distinct fecal microbiota, and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.

KW - Moderate to severe childhood asthma

KW - gut microbiota

KW - inflammatory markers

KW - metabotyping

KW - precision medicine

UR - http://www.scopus.com/inward/record.url?scp=105004927260&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2025.04.017

DO - 10.1016/j.jaci.2025.04.017

M3 - Article

C2 - 40280190

SN - 0091-6749

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

ER -

Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation

Abstract

Bibliographical note

Keywords

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