Glyphosate: Impact on the microbiota-gut-brain axis and the immune-nervous system, and clinical cases of multiorgan toxicity.

Glyphosate (GLP) and GLP-based herbicides (GBHs), such as polyethoxylated tallow amine-based GLP surfactants (GLP-SH), developed in the late 70', have become the most popular and controversial agrochemicals ever produced. Nowadays, GBHs have reached 350 million hectares of crops in over 140 countries, with an annual turnover of 5 billion and 11 billion USD in the U.S.A. and worldwide, respectively. Because of the highly efficient inhibitory activity of GLP targeted to the 5-enolpyruvylshikimate-3-phosphate synthase pathway, present in plants and several bacterial strains, the GLP-resistant crop-based genetic agricultural revolution has decreased famine and improved the costs and quality of living in developing countries. However, this progress has come at the cost of the 50-year GBH overuse, leading to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide farm and companies' workers. According to preclinical and clinical studies covered in the present review, poisoning with GLP, GLP-SH, and GBHs devastatingly affects gut microbiota and the microbiota-gut-brain (MGB) axis, leading to dysbiosis and gastrointestinal (GI) ailments, as well as immunosuppression and inappropriate immunostimulation, cholinergic neurotransmission dysregulation, neuroendocrinal system disarray, and neurodevelopmental and neurobehavioral alterations. Herein, we mainly focus on the contribution of gut microbiota (GM) to neurological impairments, e.g., stroke and neurodegenerative and neuropsychiatric disorders. The current review provides a comprehensive introduction to GLP's microbiological and neurochemical activities, including deviation of the intestinal Firmicutes-to-Bacteroidetes ratio, acetylcholinesterase inhibition, excitotoxicity, and mind-altering processes. Besides, it summarizes and critically discusses recent preclinical studies and clinical case reports concerning the harmful impacts of GBHs on the GI tract, MGB axis, and nervous system. Finally, an insightful comparison of toxic effects caused by GLP, GBH-SH, and GBHs is presented. To this end, we propose a first-to-date survey of clinical case reports on intoxications with these herbicides.