Despite growing evidence of a connection between diet, the gut microbiome, and neurodegenerative diseases, the exact relationship remains unclear. The NeuroTOm project aims to deepen our understanding of the diet-gut microbiome-brain axis and contribute to the prevention of these diseases. Using tomatoes as a model food, the project applied state-of-the-art targeted and non-targeted analytical methods (LC-MS/MS, GC-MS/MS) to identify neuroactive compounds in tomatoes and investigate the fate of these compounds during digestion, fermentation, and their impact on the gut microbiome using in vitro digestion and colon models. Neurodegenerative diseases are debilitating conditions affecting millions worldwide, including over 7 million Europeans. Although the etiology of these disease is complex, growing evidence suggests that dietary factors may influence their progression. Tomatoes, a widely consumed vegetable, are rich in bioactive compounds like phenolics, carotenoids, and glycoalkaloids, which show potential neuroprotective properties. However, most research has focused on specific nutrients, often overlooking neuro-disrupting compounds in tomato-based products, such as mycotoxins, pesticides, and industrial chemical residues. This raises concerns about the overall nutritional benefits and the impact of these contaminants on the gut microbiome and brain health. Moreover, many compounds remain unidentified, complicating efforts to link dietary exposure to human health outcomes. To address this knowledge gap, the objective of our project was to develop advanced analytical techniques to characterize both beneficial and harmful neuroactive compounds in tomato-based products, providing a better understanding of human exposure through food digestion. Understanding the biological effects of neuroactive compounds requires investigating what happens to these compounds after digestion. Bioavailability depends on factors like digestive stability, release from the food matrix, metabolic behavior, and trans-epithelial passage. However, there is limited knowledge about the in vitro gastrointestinal digestion of tomato-based products. Existing studies often focus on individual neuroprotective compounds, neglecting the interactions between these and neuro-disrupting substances. It remains unclear how neuro-disrupting compounds may influence the fate of neuroprotective compounds and their effect on the gut microbiome during digestion. Within the scope of this project, we aimed to increase knowledge about the fate of neuroactive compounds once they enter the gastrointestinal tract and how this affects the gut microbiome.