Low-dose glyphosate exposure alters gut microbiota composition and modulates gut homeostasis

The widespread use of glyphosate, a broad-spectrum herbicide, has resulted in significant human exposure, and recent studies have challenged the notion that glyphosate is completely safe for humans. Although the link between disease states and glyphosate exposure is increasingly appreciated, the mechanistic links between glyphosate and its toxic effects on human health are poorly understood, partly because no cellular targets of glyphosate have been identified. Recent studies have suggested that glyphosate may cause toxicity through modulation of the gut microbiome, but evidence for glyphosate-induced gut dysbiosis and its effect on host physiology at doses similar to the US Acceptable Daily Intake (ADI = 1.75 mg/kg body weight) is limited. Here, utilizing shotgun metagenomic sequencing of fecal samples from C57BL/6J mice exposed to different doses of glyphosate, we show that glyphosate exposure at doses similar to the U.S ADI significantly impacts gut microbiota composition. These gut microbial alterations were also associated with increased proinflammatory CD4+IL17+ T cells and Lipocalin-2, a known marker of intestinal inflammation. Finally, a decrease in fecal and serum serotonin levels was observed after glyphosate exposure. We conclude that long-term glyphosate exposure at doses similar to the U.S ADI leads to gut dysbiosis with biologically relevant effects on host physiology including a reduction of anti-inflammatory and enrichment of proinflammatory pathways.