The first 1000 days of life matter: How endocrine disrupting chemicals affect the microbial and immunological imprinting of the gut

• Applicant: Dr. Florence Fischer
• Subject Area: Gastroenterology ; Immunology ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Reproductive Medicine, Urology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 508974529

The influence of the intestinal microbiota on health reaches far beyond the gut, conferring it the title of an “additional human organ”. Notably, the symbiosis between humans and microbes, which evolves within only about 1000 days from the time of conception, is substantially involved in the maturation of the immune system. However, the tremendous importance of the intestinal bacteria for our health also implies that a disturbance of the microbiota may lead to medical issues, such as an increased susceptibility to intestinal inflammation. A lack of dietary fiber or antibiotic use can upset the bacterial community and thus the intestinal homeostasis. Man-made, endocrine-disrupting environmental chemicals (EDCs) are also among the potential disruptive factors, since the microbiota interacts closely with the human endocrine system. Yet, the direction and extent of the influence of EDCs on gut microbes remain not fully understood. In particular, we are challenged by a big gap of knowledge regarding the aspect of cumulative exposure to several EDCs at the same time, as organisms are exposed to in their natural environment. It has hardly been investigated to date, whether different chemicals can enhance or mitigate each other's biological effects. This understanding is of the utmost importance for the risk assessment of these substances. The aim of the present study is to investigate the cumulative effects of the exposure to two widely distributed EDCs - bisphenol A and benzophenone-3 - during pregnancy and breastfeeding on the microbial and immunological imprinting of the gut. We will elucidate which time windows in early development are particularly sensitive to the influence of EDCs. In addition, we will shed light on the causal relationships between a microbiota altered by exposure to EDCs and the effects on the immune system. We will use state-of-the-art methods such as 16S rRNA gene amplicon analysis, mass flow cytometry, imaging mass cytometry, and gnotobiotic in vivo models to obtain a comprehensive overview of the effects of EDCs on the gut microbiota and the immune system. Our study is dedicated to a yet hardly investigated but nevertheless important target of EDCs: the intestinal microbiota. In particular, it contributes to the urgently needed knowledge about cumulative exposure scenarios and serves as the basis for regulations on how to deal with EDCs in politics, industry and society. Our study thus contributes significantly to sustaining our health-promoting environment - today and in the future.

• DFG Programme: Research Grants