Neonatal metabolome of caesarean section and risk of childhood asthma
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Neonatal metabolome of caesarean section and risk of childhood asthma. / Gürdeniz, Gözde; Ernst, Madeleine; Rago, Daniela; Kim, Min; Courraud, Julie; Stokholm, Jakob; Bønnelykke, Klaus; Björkbom, Anders; Trivedi, Urvish; Sørensen, Søren J.; Brix, Susanne; Hougaard, David; Rasmussen, Morten; Cohen, Arieh S; Bisgaard, Hans; Chawes, Bo.
In: The European Respiratory Journal, Vol. 59, No. 6, 2102406, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Neonatal metabolome of caesarean section and risk of childhood asthma
AU - Gürdeniz, Gözde
AU - Ernst, Madeleine
AU - Rago, Daniela
AU - Kim, Min
AU - Courraud, Julie
AU - Stokholm, Jakob
AU - Bønnelykke, Klaus
AU - Björkbom, Anders
AU - Trivedi, Urvish
AU - Sørensen, Søren J.
AU - Brix, Susanne
AU - Hougaard, David
AU - Rasmussen, Morten
AU - Cohen, Arieh S
AU - Bisgaard, Hans
AU - Chawes, Bo
N1 - Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.
PY - 2022
Y1 - 2022
N2 - BACKGROUND: Birth by cesarean section (CS) is linked to an increased risk of developing asthma, but the underlying mechanisms are unclear.OBJECTIVE: To elucidate the link between birth by CS and asthma using newborn metabolomic profiles and integrating early life gut microbiome data and cord blood immunology.METHODS: We investigated the influence of CS on liquid chromatography mass spectrometry (LC-MS) metabolomic profiles of dried blood spots from newborns of the two independent Copenhagen Prospective Studies on Asthma in Childhood cohorts, i.e. COPSAC2010 (n=677) and COPSAC2000 (n=387). We assessed the associations between the CS metabolic profile, age one-week gut microbiome data and frequency of cord blood Tregs. RESULTS: In COPSAC2010, a partial least square-discriminant analysis (PLS-DA) model showed that children born by CS versus natural delivery had different metabolic profiles (AUC=0.77, p=2.2e-16), which was replicated in COPSAC2000 (AUC=0.66, p=1.2e-5). The metabolic profile of CS was significantly associated with an increased risk of asthma at school-age in both COPSAC2010 (p=0.03) and COPSAC2000 (p=0.005). CS was associated with lower abundance of tryptophan, bile acid and phenylalanine metabolites, indicative of a perturbed gut microbiota. Further, gut bacteria dominating after natural delivery, i.e. Bifidobacterium and Bacteroides were correlated with CS-discriminative microbial metabolites, suggesting maternal microbial transmission during birth regulating the newborn's metabolism. Finally, the CS metabolic profile was associated with frequency of cord blood Tregs. CONCLUSIONS: These findings propose that CS is programming the risk of childhood asthma through perturbed immune responses and gut microbial colonization patterns reflected in the blood metabolome at birth.
AB - BACKGROUND: Birth by cesarean section (CS) is linked to an increased risk of developing asthma, but the underlying mechanisms are unclear.OBJECTIVE: To elucidate the link between birth by CS and asthma using newborn metabolomic profiles and integrating early life gut microbiome data and cord blood immunology.METHODS: We investigated the influence of CS on liquid chromatography mass spectrometry (LC-MS) metabolomic profiles of dried blood spots from newborns of the two independent Copenhagen Prospective Studies on Asthma in Childhood cohorts, i.e. COPSAC2010 (n=677) and COPSAC2000 (n=387). We assessed the associations between the CS metabolic profile, age one-week gut microbiome data and frequency of cord blood Tregs. RESULTS: In COPSAC2010, a partial least square-discriminant analysis (PLS-DA) model showed that children born by CS versus natural delivery had different metabolic profiles (AUC=0.77, p=2.2e-16), which was replicated in COPSAC2000 (AUC=0.66, p=1.2e-5). The metabolic profile of CS was significantly associated with an increased risk of asthma at school-age in both COPSAC2010 (p=0.03) and COPSAC2000 (p=0.005). CS was associated with lower abundance of tryptophan, bile acid and phenylalanine metabolites, indicative of a perturbed gut microbiota. Further, gut bacteria dominating after natural delivery, i.e. Bifidobacterium and Bacteroides were correlated with CS-discriminative microbial metabolites, suggesting maternal microbial transmission during birth regulating the newborn's metabolism. Finally, the CS metabolic profile was associated with frequency of cord blood Tregs. CONCLUSIONS: These findings propose that CS is programming the risk of childhood asthma through perturbed immune responses and gut microbial colonization patterns reflected in the blood metabolome at birth.
U2 - 10.1183/13993003.02406-2021
DO - 10.1183/13993003.02406-2021
M3 - Journal article
C2 - 34887324
VL - 59
JO - The European Respiratory Journal
JF - The European Respiratory Journal
SN - 0903-1936
IS - 6
M1 - 2102406
ER -
ID: 300909150