Neuroactive compounds in tomatoes: metabolic fate during in vitro digestion and colonic fermentation

Neurodegenerative diseases are hard to treat, and their progression is linked to diet and the gut microbiota. Tomatoes contain potentially neuroactive compounds, but their fate during digestion and colonic fermentation remains unclear. This study tracked neuroactive compounds and fecal fatty acids (<C12) during in vitro gastrointestinal digestion and fecal fermentation. Conditions included a fecal blank, digested inulin, digested tomato, tomato with neuro-disrupting compounds, and individual neuroprotective compounds. Targeted analyses and linear mixed-effects models showed samples were primarily differentiated by tomato presence and fermentation time. Several neuroprotective compounds (e.g., tomatine, serotonin) remained stable (>50%, 24 h) or increased, whereas others (e.g., caffeic acid, rutin) degraded rapidly (<LOQ, 3 h). Neuro-disrupting compounds, including bisphenol S and difenoconazole, persisted largely unchanged (>80%, 24 h). Digested tomato enhanced acetic and propionic acid production, though attenuated by neuro-disruptors. The study clarifies colonic bioaccessibility of neuroactive compounds and their potential influence on the gut–brain axis. • Tracked 36 neuroactive compounds during in vitro digestion and fecal fermentation. • Tomato and fermentation time drive differentiation in fecal metabolite profiles. • Tomato digestion boosts colonic bioavailability of neuroprotective compounds. • Neuro-disrupting compounds show high stability and persist in the gut. • Tomato promotes SCFA production, but neuro-disruptors weaken this response.