Emetic foodborne toxins — including bacterial enterotoxins, deoxynivalenol (DON), zearalenone (ZEA), cereulide, T-2 toxin, domoic acid, and histamine — trigger acute gastrointestinal responses via brainstem area postrema (AP) activation and chronic systemic pathology through the AP–hypothalamus–locus coeruleus (LC) neuroendocrine axis. Key receptor pathways implicated include GLP-1R, CCK, PYY, ghrelin, GDF15-GFRAL, and 5-HT3. Chronic exposure drives cachexia-like metabolic reprogramming, neuropsychiatric dysfunction, and multi-organ failure, with gut dysbiosis and LPS translocation amplifying systemic inflammation.
This review arrives at a moment when the GDF15-GFRAL axis is attracting intense pharmaceutical interest as a cachexia and anorexia target — making its identification here as a toxin-exploited pathway clinically significant. The framing of acute-to-chronic toxin cascades through a unified neuro-metabolic network is conceptually valuable, connecting food safety, geriatric medicine, and neurology in ways that fragmented literature rarely does. The elderly are specifically flagged as high-risk due to immunosenescence, compromised barrier integrity, and polypharmacy — a convergence that makes subclinical chronic toxin exposure a plausible but underappreciated contributor to unexplained muscle wasting and cognitive decline in aging populations. Critical limitation: this is a review, not primary data, so mechanistic claims rest on synthesized evidence of variable quality across toxin types. The practical implication for clinicians is compelling nonetheless — chronic low-level mycotoxin exposure in elderly patients with unexplained cachexia deserves renewed investigative attention.
