Effects of arylhydrocarbon receptor ligands 2,3,7,8-TCDD and dietary indole-3-carbinol on the gut microbiome, immune-mediated barrier function and metabolism

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Adverse effects on the immune system and metabolism are characteristic harmful effects of dioxins and other so-called persistent organic pollutants (POPs). These pollutants are still present in the environment. POP pollution is of particular concern in developing countries, as appropriate emission control is often lacking. Dioxins bind to the endogenous transcription factor aryl hydrocarbon receptor (AHR), and thereby control cellular gene programs. The main route of exposure for dioxins is food. It is therefore surprising that very few studies exist which look at the effects of dioxin on the intestine and the intestinal immune system. Recent research using AHR-deficient mice has shown that the AHR is necessary for a functioning intestinal immune system and the balance of commensal versus pathogenic intestinal bacteria. Indeed, interest has increased dramatically in the microbiome as an important player in (gut) immunity and health. Activation of the AHR (e.g. by certain phytochemicals or products of by gut bacteria) prevent inflammatory processes. Lack of AHR or a lack of AHR ligands in the diet can lead to increased susceptibility to certain infections. Food ingredients are important to stimulate the AHR signaling and regulate the gut microbiome. In contrast, it is almost completely unknown whether and how dioxins and other persistent organic pollutants damage the gut microbiome, and thus might adversely affect gut immunity or metabolic health. We want to address this gap using the mouse model. We will examine for the first time which microbial changes are caused by dioxin exposure, and what consequences this has for immune barrier function and in the context of a Western-diet. We will furthermore establish and use a novel screening method by flow-cytometric measurements of microbiome patterns. Our results are (i) important for better risk assessment for dioxins themselves and other environmentally relevant AHR ligands, and (ii) for the approaches, using dietary AHR ligands to influence the gut microbiome, intestinal immune system, and metabolism positively.