Altered stress responses in adults born by Caesarean section

Timothy G Dinan; Paul J Kennedy; Livia H Morais; Amy Murphy; Caitriona M Long-Smith; Gerard M Moloney; Thomaz F S Bastiaanssen; Andrew P Allen; Aoife Collery; David Mullins; Anne-Marie Cusack; Kirsten Berding; Paul W O'Toole; Gerard Clarke; Catherine Stanton; John F Cryan

doi:10.1016/j.ynstr.2021.100425

Altered stress responses in adults born by Caesarean section

Neurobiol Stress. 2021 Dec 28:16:100425. doi: 10.1016/j.ynstr.2021.100425. eCollection 2022 Jan.

Authors

Timothy G Dinan^{1

2}, Paul J Kennedy^{1

2}, Livia H Morais¹, Amy Murphy^{1

3}, Caitriona M Long-Smith¹, Gerard M Moloney⁴, Thomaz F S Bastiaanssen¹, Andrew P Allen^{1

2}, Aoife Collery¹, David Mullins¹, Anne-Marie Cusack¹, Kirsten Berding¹, Paul W O'Toole^{1

3}, Gerard Clarke^{1

2}, Catherine Stanton^{1

2

3}, John F Cryan^{1

4}

Affiliations

¹ APC Microbiome Ireland, University College Cork, Cork, Ireland.
² Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
³ Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
⁴ Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.

Abstract

Birth by Caesarean-section (C-section), which increases the risk for metabolic and immune disorders, disrupts the normal initial microbial colonisation of the gut, in addition to preventing early priming of the stress and immune-systems.. Animal studies have shown there are enduring psychological processes in C-section born mice. However, the long-term impact of microbiota-gut-brain axis disruptions due to birth by C-section on psychological processes in humans is unknown. Forty age matched healthy young male university students born vaginally and 36 C-section delivered male students were recruited. Participants underwent an acute stressor, the Trier social stress test (TSST), during a term-time study visit. A subset of participants also completed a study visit during the university exam period, representing a naturalistic stressor. Participants completed a battery of cognitive tests and self-report measures assessing mood, anxiety, and perceived stress. Saliva, blood, and stool samples were collected for analysis of cortisol, peripheral immune profile, and the gut microbiota. Young adults born by C-section exhibit increased psychological vulnerability to acute stress and a prolonged period of exam-related stress. They did not exhibit an altered salivary cortisol awakening response to the TSST, but their measures of positive affect were significantly lower than controls throughout the procedure. Both C-section and vaginally-delivered participants performed equally well on cognitive assessments. Most of the initial effects of delivery mode on the gut microbiome did not persist into adulthood as the gut microbiota profile showed modest changes in composition in adult vaginally-delivered and C-sectioned delivered subjects. From an immune perspective, concentrations of IL-1β and 1L-10 were higher in C-section participants. These data confirm that there is a potential enduring effect of delivery mode on the psychological responses to acute stress during early adulthood. The mental health implications of these observations require further study regarding policies on C-section use.

Keywords: Caesarean section; Cognition; Microbiome; Stress.