C-section increases cecal abundance of the archetypal bile acid and glucocorticoid modifying Lachnoclostridium [Clostridium] scindens in mice

Authors: ADAMS, SEAN - University Of California, Davis; WRIGHT, RACHEL - University Of California, Davis; PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); MOODY, BECKY - Arkansas Children'S Nutrition Research Center (ACNC); SIKES, JAMES - Arkansas Children'S Nutrition Research Center (ACNC); AVARITT, NATHAN - University Arkansas For Medical Sciences (UAMS); CHINTAPALLI, SREE - Arkansas Children'S Nutrition Research Center (ACNC); OU, XIAWEI - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Physiological Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2022
Publication Date: 7/1/2022
Citation: Adams, S.H., Wright, R., Piccolo, B.D., Moody, B., Sikes, J., Avaritt, N., Chintapalli, S.V., Ou, X. 2022. C-section increases cecal abundance of the archetypal bile acid and glucocorticoid modifying Lachnoclostridium [Clostridium] scindens in mice. Physiological Reports. Volume 10, Issue 13. https://doi.org/10.14814/phy2.15363.
DOI: https://doi.org/10.14814/phy2.15363

Interpretive Summary: In humans and animal models, Cesarean section (C-section) has been associated with changes of microbiota population in the gut. However, it is not clear if birth mode inherently changes that, or if C-section effects involve interactions with environmental and other factors. In this study, we measured and compared cecal microbiota in 3 week old mice born by C-section or natural delivery, while making sure other factors such as housing, cross-fostering, diet, sex, and genetic strain were the same among these two groups. We found that main microbiota measures such as alpha and betta diversity were not different between groups. Only the abundance of one out of 601 species showed group difference. Our results suggest that C-section does not inherently lead to large-scale changes in gut microbiota populations.

Technical Abstract: In humans and animal models, Cesarean section (C-section) has been associated with alterations in the taxonomic structure of the gut microbiome. These changes in microbiota populations are hypothesized to impact immune, metabolic, and behavioral/neurologic systems and others. It is not clear if birth mode inherently changes the microbiome, or if C-section effects are context-specific and involve interactions with environmental and other factors. To address this and control for potential confounders, cecal microbiota from ~3 wk old mice born by C-section (n=16) vs. natural birth (n=23) were compared under matched conditions for housing, cross fostering, diet, sex and genetic strain. A total of 601 unique species were detected across all samples. Alpha diversity richness (i.e., how many species within sample; Chao1) and evenness/dominance (i.e., Shannon, Simpson, Inverse Simpson) metrics revealed no significant differences by birth mode. Beta diversity (i.e., differences between samples), as estimated with Bray-Curtis dissimilarities and Aitchison distances (using log(x+1)-transformed counts), was also not significantly different (Permutational Multivariate ANOVA [PERMANOVA]). Only the abundance of Lachnoclostridium [Clostridium] scindens was found to differ using a combination of statistical methods (ALDEx2, DESeq2), being significantly higher in C-section mice. This microbe has been implicated in secondary bile acid production and regulation of glucocorticoid metabolism to androgens. From our results and the extant literature we conclude that Csection does not inherently lead to large-scale shifts in gut microbiota populations, but birth mode could modulate select bacteria in a context-specific manner: e.g., involving factors associated with pre-, peri- HJ, and postpartum environments, diet or host genetics.