AOPs to connect food additives' effects on gut microbiota to health outcomes.

Gut microbiota play a central role in human health, notably through the production of metabolites, including short-chain fatty acids, secondary bile acids, vitamins or neurotransmitters. Beyond contributing to gut health, these microbial metabolites significantly impact multiple organ systems by activating key signaling pathways along the gut-organ axes, including the gut-liver, gut-brain, and gut-bone axes. Chemicals ingested through food such as food additives, extensively used to enhance the texture, preservation and appearance of foods, may interact with our gut microbiota, altering metabolite production, and this can have consequences for our health. However, gut microbial metabolism is currently overlooked in toxicology. While efforts are underway to develop standardized human-based new approach methodologies to assess compound-microbiome interactions, anchoring those assays within the adverse outcome pathway (AOP) framework would offer a structured way to connect changes in gut microbial metabolism to adverse health outcomes. Using human-based models enhances the relevance of the results while supporting the reduction of animal-based testing in toxicology research.