Objectives and overview of the action:

This proposal aims to determine which neuroactive chemicals people are exposed to through food (tomato), their fate once entering the human body, and how this could impact the development of ND diseases, i.e., from ingestion to digestion, while considering the effects of neuro-disrupting compounds.

Objective 1 (O1): Characterise neuroactive compounds in tomatoes (organic, conventional, and processed). The project will adapt existing target and non-target based (suspect screening) workflows to characterise neuroprotective (e.g., carotenoids, flavonoids) and neuro-disrupting compounds (e.g., pesticide, industrial chemical residues) in tomatoes. These methods will investigate organically and conventionally grown fresh tomatoes and a processed tomato-based product (canned tomatoes). In this way, the project will look for differences between chemical profiles of differently produced/processed tomatoes and how this affects the levels of neuroactive compounds people are exposed to when eating tomatoes. Based on the literature review, the screening will focus on compounds that could mitigate or worsen the effects of ND diseases.

Hypothesis 1: The type and amount of neuroactive compounds depend on how tomatoes are produced and processed.

Objective 2 (O2): Increase knowledge about the fate of neuroactive compounds once they enter the GI and how this affects the gut microbiome. To verify this, NeuroTOm will model the human gut microbiome using in vitro 2D batch colonic model to (1) simulate the digestion of tomato extract and faecal batch-culture fermentation to investigate the fate of selected neuroactive compounds, chosen based on the results of O1, in the gut microbiome (INFOGEST protocol); (2) determine the bioavailability of a selected number of neuroprotective compounds and neuro-disrupting compounds present in tomatoes; (3) identify the selected ND-associated neuroactive substances' GMMs, and (4) determine how neuroprotective/neuro-disrupting compounds affect the gut microbiome, i.e., by monitoring gut microbiota composition, SCFA and ROS production.

Hypothesis 2: Neuro-disrupting compounds in tomatoes and their GMMs change the bioavailability of ND related neuroprotective compounds and alter the gut microbiota composition, SCFA and ROS production.

Objective 3 (O3): Measure the effects of neuroactive substances from a tomato-based diet on IECs and their potential to affect the GBA by using IOs. The results will provide essential information for understanding the impact of dietary nutrition on ND diseases by determining how neuroprotective and neuro-disrupting compounds and their GMMs affect IECs, and, in turn, their uptake. This work will also look at how they will affect the GBA (cell viability, ROS, apoptosis, and intestinal permeability) using a novel 3D in vitro colon organoid alone and in the presence of neurodisrupting compounds. 

Hypothesis 3: The presence of neuro-disrupting compounds can affect the favourable properties of ND neuroprotective compounds measured using a colon organoid.