Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 23;59(6):2102406.
doi: 10.1183/13993003.02406-2021. Print 2022 Jun.

Neonatal metabolome of caesarean section and risk of childhood asthma

Gözde Gürdeniz  1 , Madeleine Ernst  2 , Daniela Rago  1 , Min Kim  1 , Julie Courraud  2 , Jakob Stokholm  1 , Klaus Bønnelykke  1 , Anders Björkbom  2 , Urvish Trivedi  3 , Søren J Sørensen  3 , Susanne Brix  4 , David Hougaard  2 , Morten Rasmussen  1   5 , Arieh S Cohen  2 , Hans Bisgaard  1 , Bo Chawes  6
Affiliations
Free article

Neonatal metabolome of caesarean section and risk of childhood asthma

Gözde Gürdeniz et al. Eur Respir J. .
Free article

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: All authors declare no potential, perceived, or real conflict of interest regarding the content of this manuscript. The funding agencies did not have any role in design and conduct of the study; collection, management, and interpretation of the data; or preparation, review, or approval of the manuscript. No pharmaceutical company was involved in the study.

Publication types