RT Journal Article
SR Electronic
T1 Neonatal metabolome of caesarean section and risk of childhood asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2102406
DO 10.1183/13993003.02406-2021
VO 59
IS 6
A1 Gözde Gürdeniz
A1 Madeleine Ernst
A1 Daniela Rago
A1 Min Kim
A1 Julie Courraud
A1 Jakob Stokholm
A1 Klaus Bønnelykke
A1 Anders Björkbom
A1 Urvish Trivedi
A1 Søren J. Sørensen
A1 Susanne Brix
A1 David Hougaard
A1 Morten Rasmussen
A1 Arieh S. Cohen
A1 Hans Bisgaard
A1 Bo Chawes
YR 2022
UL http://erj.ersjournals.com/content/59/6/2102406.abstract
AB Background Birth by caesarean section is linked to an increased risk of developing asthma, but the underlying mechanisms are unclear.Objective To elucidate the link between birth by caesarean section and asthma using newborn metabolomic profiles and integrating early-life gut microbiome data and cord blood immunology.Methods We investigated the influence of caesarean section on liquid chromatography mass spectrometry 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 caesarean section metabolic profile, gut microbiome data and frequency of cord blood regulatory T-cells (Tregs) at 1 week of age.Results In COPSAC2010, a partial least square discriminant analysis model showed that children born by caesarean section versus natural delivery had different metabolic profiles (area under the curve (AUC)=0.77, p=2.2×10−16), which was replicated in COPSAC2000 (AUC=0.66, p=1.2×10−5). The metabolic profile of caesarean section was significantly associated with an increased risk of asthma at school age in both COPSAC2010 (p=0.03) and COPSAC2000 (p=0.005). Caesarean section was associated with lower abundance of tryptophan, bile acid and phenylalanine metabolites, indicative of a perturbed gut microbiota. Furthermore, gut bacteria dominating after natural delivery, i.e. Bifidobacterium and Bacteroides were correlated with caesarean section-discriminative microbial metabolites, suggesting maternal microbial transmission during birth regulating the newborn's metabolism. Finally, the caesarean section metabolic profile was associated with frequency of cord blood Tregs.Conclusions These findings propose that caesarean section programmes the risk of childhood asthma through perturbed immune responses and gut microbial colonisation patterns reflected in the blood metabolome at birth.Birth by caesarean section influences the risk of asthma, partially by gut microbial colonisation and perturbed immune responses reflected by dysregulations in bile acid and tryptophan metabolism during early life https://bit.ly/3mFuqt0