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Altered stress responses in adults born by Caesarean section.

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.

SUBMITTER: Dinan TG

PROVIDER: S-EPMC8733342 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05). The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.

Project description:BackgroundCaesarean section (CS) is not recommended for PMTCT in Malawi HIV Guidelines, contrary to most high-income countries where CS is indicated if viral suppression is sub-optimal pre-delivery. We describe patterns of CS in HIV-infected and uninfected women in Malawi and explored if insight into the use of Elective CS (ECS) for PMTCT could be obtained.MethodsWe used routinely collected data from individual medical records from 17 large health facilities in the central and southern regions of Malawi, from January 2010 to December 2013. We included data from maternity registers from all HIV-positive women, and randomly selected around every fourth woman with negative or unknown HIV status. We used multivariable logistic regressions and cluster-based robust standard errors to examine independent associations of patient- and facility characteristics with CS and ECS.ResultsWe included 62,033 women in the analysis. The weighted percentage of women who had a spontaneous vaginal delivery was 80.0% (CI 95% 79.5-80.4%); 2.4% (95% CI 2.3-2.6%) had a vacuum extraction; 2.3% (95% CI 2.2-2.5%) had a vaginal breech delivery; 14.0% (95% CI 13.6-14.4%) had a CS while for 1.3% (95% CI 1.2-1.4%) the mode of delivery was not recorded. Prevalence of CS without recorded medical or obstetric indication (ECS) was 5.1%, (n = 3152). Presence of maternal and infant complications and older age were independently associated with CS delivery. HIV-positive women were less likely to have ECS than HIV negative women (aOR 0.65; 95%-CI 0.57-0.74). Among HIV-positive women, those on antiretrovirals (ARV's) for ≥4 weeks prior to delivery were less likely to have ECS than HIV-positive women who had not received ARVs during pregnancy (aOR 0.81; 95% CI 0.68-0.96).ConclusionsThe pattern of CS's in Malawi is largely determined by maternal and infant complications. Positive HIV status was negatively associated with CS delivery, possibly because health care workers were concerned about the risk of occupational HIV transmission and the known increased risk of post-operative complications. Our results leave open the possibility that CS is practiced to prevent MTCT given that ECS was more common among women at high risk of MTCT due to no or short exposure to ARV's.

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Altered stress responses in adults born by Caesarean section.

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