Cesarean section induced dysbiosis promotes type 2 immunity but not oxazolone-induced dermatitis in mice

ABSTRACT

Delivery by cesarean section (CS) is associated with an altered gut microbiota (GM) colonization and a higher risk of later chronic inflammatory diseases. Studies investigating the association between CS and atopic dermatitis (AD) are contradictive and often biased by confounding factors. The aim of this study was therefore to provide experimental evidence for the association between CS and AD in a mouse model and clarify the role of the GM changes associated with CS. It was hypothesized that CS-delivered mice, and human CS-GM transplanted mice develop severe dermatitis due to early dysbiosis. BALB/c mice delivered by CS or vaginally (VD) as well as BALB/c mice transplanted with GM from CS or VD human donors were challenged with oxazolone on the ear. The severity of dermatitis was evaluated by ear thickness and clinical and histopathological assessment which were similar between all groups. The immune response was assessed by serum IgE concentration, local cytokine response, and presence of immune cells in the draining lymph node. Both CS-delivered mice and mice inoculated with human CS-GM had a higher IgE concentration. A higher proportion of Th2 cells were also found in the CS-GM inoculated mice, but no differences were seen in the cytokine levels in the affected ears. In support of the experimental findings, a human cohort analysis from where the GM samples were obtained found that delivery mode did not affect the children’s risk of developing AD. In conclusion, CS-GM enhanced a Th2 biased immune response, but had no effect on oxazolone-induced dermatitis in mice.

KEYWORDS:

• Animal model
• atopic dermatitis
• birth mode
• bacteroides
• cesarean section
• gut microbiota
• IgE
• type 2 immunity

Acknowledgments

Data was generated through accessing research infrastructure at University of Copenhagen, including FOODHAY (Food and Health Open Innovation Laboratory, Danish Roadmap for Research Infrastructure).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Study conception and design: LFZ, MBBE, JS, CHFH; Acquisition of data: LFZ, MBBE, CMJM, LD, LK, JS, CHFH; Analysis and interpretation of data; LFZ, MBBE, CMJM, LD, LK, DNS, JS, CHFH; Drafting of manuscript: LFZ, CMJM, LD, LK, JS, CHFH; Critical revision: LFZ, AKH, DSN, TLH, PT, CHFH. Final approval: LFZ, MBBE, CMJM, LD, LK, DSN, JS, CHFH.

Data availability statement

The GM 16S sequencing dataset generated for this study can be found in the BioProject database with ID: PRJNA890556. https://eur02.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fsra%2FPRJNA890556&data=05%7C01%7Ckrych%40food.ku.dk%7C583eaab1d1694aee1d4b08daaf3fdc60%7Ca3927f91cda14696af898c9f1ceffa91%7C0%7C0%7C638014986071254893%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=5ifUQY8qHZEIoHy%2B6k8depDvB33WZfwKu2LfaJyfAi0%3D&reserved=0

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2271151

Additional information

Funding

The study was supported by the Independent Research Fund Denmark under grant no. 8045-00008B.