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It is the first neural system exposed to food contaminants (FCs)\u2014a diverse group of ubiquitous toxic compounds fortuitously present in food derived from production, processing, storage, or environmental contamination. Emerging evidence suggests that FCs may initiate or amplify neurodegenerative processes, yet their effects on the ENS and their impact in gut\u2010to\u2010brain communication remain insufficiently characterized. This systematic review synthesizes current evidence on FCs\u2010induced effects on the ENS and its involvement in mediating neurotoxicity from dietary toxicants exposure. Following PRISMA guidelines, 67 studies were included pertaining to cellular or mammalian experimental models exposed to FCs via enteral routes, reporting ENS\u2010related outcomes or studying vagal involvement in modulating FC toxicity. The main FCs evaluated were pesticides, toxins, bisphenols, acrylamide, manganese, and micro\u2010\/nanoplastics. Across studies, FCs consistently induced neurochemical remodeling of the ENS, activation of enteric glia, often coupled with intestinal alterations. Rotenone, paraquat, and polystyrene micro\u2010\/nanoplastics promote \u03b1\u2010synuclein aggregation within the ENS and its vagal propagation to the brain. Vagotomy models confirmed that disrupting ENS\u2013CNS communication attenuates FC\u2010related central neurotoxicity, supporting the involvement of food toxicants in gut\u2010to\u2010brain propagation of neurotoxic signals. These findings support the\n                    <jats:italic>body\u2010first<\/jats:italic>\n                    hypothesis of PD and position the ENS as a critical, yet underinvestigated interface in exposome\u2010related neurotoxicology. The review highlights research gaps and the need for improved models and long\u2010term, low\u2010dose studies reflecting realistic FC exposure.\n                  <\/jats:p>","DOI":"10.1111\/1541-4337.70448","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T04:26:43Z","timestamp":1775795203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enteric Nervous System Damage by Food Contaminants: A Pathway to Neurodegeneration?"],"prefix":"10.1111","volume":"25","author":[{"given":"Helena","family":"Ramos","sequence":"first","affiliation":[{"name":"LAQV\u2010REQUIMTE, Laboratory of Bromatology and Hydrology, Faculty of Pharmacy University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Margarida","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE, Laboratory of Bromatology and Hydrology, Faculty of Pharmacy University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-1431","authenticated-orcid":false,"given":"Isabel M. 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