FLEXiGUT : investigating the importance of the exposome in the development and progression of chronic low-grade gut inflammation

Exposure to environmental and dietary contaminants, such as toxins, man-made chemicals and air pollution, is suspected to disturb gut homeostasis and have a negative impact on human health. Several studies have, moreover, associated microbiome alterations with common chronic diseases such as obesity, diabetes, and colorectal cancer. Interestingly, the Bacteroides2 enterotype has recently been linked to gut inflammation as well as to systemic inflammation, revealing the existence of a gut microbiome-inflammatory axis [1]. The gut microbiota appears to play a central role in inflammation owing to its ability to release inflammatory products, which may contribute to biological processes that increase the risk of chronic diseases and/or accelerate biological ageing. FLEXiGUT - the Flemish exposome project- is the first large-scale study focused on investigating the importance of the exposome in the development and progression of chronic low-grade gut inflammation both in children and adults [2]. To this end, we combine exposure records and high-throughput omics technologies with epidemiological studies. We investigate subsets two Flemish prospective cohorts that cover the human life course: the ENVIRONAGE mother-child cohort which provides follow-up from gestation to the age of 10 years (N=400), and the Flemish Gut Flora Project longitudinal cohort in predominantly healthy adults (N=400). We leverage three main sources of data that positions FLEXiGUT at the forefront of microbiome-exposome interaction research. The data sources include but are not limited to: 1) rich metadata including geolocation, drug intake, dietary intake and lifestyle; 2) biomonitoring of environmental and dietary contaminants in biofluids and tissues such as urine, blood and placenta generated by FLEXiGUT; and 3) extensive multi-omics data generated by FLEXiGUT including fecal metagenomics, metabolomics, and DNA adductomics, telomere length as a marker for biological ageing, and inflammatory markers. These unique datasets will enable to obtain a deep insight into the relationship of environmental and dietary exposures on various biological parameters at high precision. This will pave the way for targeted biomarker discovery and predictive analytics for diseases linked to chronic low-grade gut inflammation and will shed light on the early molecular events within pathways leading to the development of diseases.