Neurochemical Remodelling of the Enteric Nervous System Neurons in the Porcine Jejunum Following Low-Dose Glyphosate Exposure

Glyphosate, a widely used herbicide, is under scrutiny for its potential neurotoxic effects. This study investigated whether oral exposure to glyphosate, even at doses currently considered safe in Europe, alters the neurochemical profile of enteric nervous system (ENS) neurons in the porcine jejunum. Fifteen immature female pigs were allocated to three groups: control (C), low-dose (G50; 50 µg/kg b.w./day), and higher-dose (G500; 500 µg/kg b.w./day). Following 28 days of exposure, jejunal samples were subjected to double-labelling immunofluorescence staining for neuronal markers, including Hu C/D and PACAP, CGRP, CART, nNOS, or VAChT. Results revealed dose-dependent neurochemical alterations across all enteric plexuses, with glyphosate increasing the number of neurons expressing PACAP, CGRP, CART, and nNOS, while reducing VAChT-positive neurons. The effect of glyphosate on enteric neurons appeared largely uniform across different plexus types, with more pronounced changes at the higher dose and only minor regional variation. Overall, the findings suggest that glyphosate exposure, even within regulatory limits, may alter the neurochemical profile of enteric neurons in a broadly uniform manner, potentially reflecting responses to oxidative stress or early neurotoxic effects, as reported in previous studies. This study challenges current safety thresholds and emphasises the need to reassess regulatory guidelines, particularly in the context of chronic exposure and potential risks to vulnerable populations.