Antibiotic use during pregnancy and increased risk for allergic asthma in the next generation
Scientific interest within the context of the graduate college:
The most exciting phrase to hear in science, the one that heralds new discoveries, is not ‘Eureka!’ but ‘That’s funny…’ – Isaac Asimov –
We are a reproductive immunology group studying pregnancy, allergy and immune system development. The Developmental Origins of Health and Disease hypothesis posits that perinatal environmental exposures, during the fetal and early neonatal life stages, can influence childhood immune system development and alter disease susceptibility later in life. Demonstrating this, epidemiological studies show that the use of antibiotics during pregnancy is associated with an increased risk for allergic asthma in childhood.1 Since antibiotics account for 80% of the medications prescribed during pregnancy, it is increasingly important to understand the connection between prenatal antibiotic exposure and allergic asthma risk. To study this, we recently designed a model in which treatment of pregnant mice with the antibiotic vancomycin resulted in increased severity of allergic asthma in the offspring. We found that antibiotic treatment during pregnancy caused detrimental changes to the maternal gut microbiome, known as microbial dysbiosis, which was then passed on to the offspring.2 In early neonatal life, the gut microbiome interacts very closely with the developing immune system, and we found that the transfer of an antibiotic-altered gut microbiome from mother to offspring programs the immune system to become hyperreactive, which likely increases offspring asthma susceptibility. We would like to further this research by testing possible treatments, such as supplementation with probiotics or immunomodulatory short-chain fatty acids, that can help the maternal gut microbiome recover after exposure to antibiotics during pregnancy.
Project description:
Your project will use our established mouse model to test supplementation strategies to counteract the detrimental effects of antibiotic use in pregnant mice, with the goal to rescue the offspring from increased asthma risk. The following key questions will be addressed as the main theme for the project:
1.) Can maternal supplementation with short-chain fatty acids, pre- or probiotics alter antibiotic-induced gut microbial dysbiosis in pregnant mice?
2.) How do these treatments influence the development of the fetal and/or neonatal immune systems?
3.) Do any of these treatments protect against allergic asthma in the offspring?
To accomplish this, you will be trained in all aspects of mouse handling, reproductive strategies, and treatment as well as in asthma induction and analysis of tissue inflammation. In addition to learning animal work and basic molecular biology techniques in the laboratory, your project will include major methods, such as microscopy, flow cytometry, and gut microbiome analysis. Also, as we are using a transgenerational model, there are many possibilities; if you would like to learn a specific technique not listed here, or are interested in a particular developmental time point i.e., placentation, fetal development, lactation, or neonatal development, we are flexible to discuss possibilities.
References
- Cait A, Wedel A, Arntz JL, Duinkerken J, Datye S, Cait J, Alhasan MM, Conrad ML. Prenatal antibiotic exposure, asthma, and the atopic march: A systematic review and meta-analysis. Allergy. 2022; 77:3233-3248. doi:10.1111/all.15404.
- Alhasan M, Heimesaat M, Blaut M, Klopfleisch R, Yildirim AÖ, Cait A, Bereswill S, Conrad ML. Prenatal exposure to antibiotics increases offspring asthma severity in a dose-dependent manner. Allergy. 2020; 75:1975-1986. doi:10.1111/all.14234.