Even extremely small amounts of the herbicide glyphosate can harm gut health, disrupt metabolism, and change behavior in mice, scientists say. The effects aren’t limited to the exposed animals—they pass on to their children and grandchildren.

The new research, to be published Nov. 1 in Science of the Total Environment, suggests that prenatal exposure to glyphosate disrupts gut bacteria, hormones, and brain signaling in mice. Even at doses far below current safety guidelines, the herbicide is linked to inflammation, metabolic problems involving appetite and blood sugar, and signs of neurological risk.

“Our findings demonstrate that prenatal glyphosate exposure, at doses consistent with real-world dietary intake, can disrupt multiple physiological systems across generations,” the researchers say. 

Glyphosate, best known as the active ingredient in Roundup^®, is the most widely used herbicide in the world, with more than 160 million kilograms applied annually in North America. Once thought safe because it targets a plant-specific pathway absent in humans, glyphosate may still indirectly harm people by disrupting gut microbes, immune responses, and hormone systems — especially during pregnancy and early life, according to emerging evidence.

Exposure to glyphosate has been linked to cancer, liver and kidney disease, endocrine disruption, fertility issues, neurotoxicity, and other health concerns, despite industry pushback. Earlier this year, research showed glyphosate significantly harmed the health of babies in rural U.S. communities over the past two decades, especially those already at risk of poor birth outcomes. 

Other long-term studies, such as the CHAMACOS cohort, link early-life glyphosate exposure to higher risks of liver and cardiometabolic disorders by age 18.  

This study, conducted by researchers at the University of British Columbia and the University of Alberta in Canada, shows mice exposed to glyphosate before birth were less active overall, moved shorter distances and at slower speeds, and showed weaker working memory (the ability to store and process information). The mice also explored less, suggesting reduced curiosity or mild movement difficulties.

Prenatal exposure caused microscopic inflammation, similar to that observed in early-stage colon inflammation (colitis). Gut damage, loss of protective mucus, and chronic inflammation persisted in the grandchildren (F2 generation).

Other key findings include:

• Metabolic problems: Offspring had difficulty processing sugar, exhibited insulin resistance, and produced lower levels of GLP-1, a hormone that regulates blood sugar.
• Microbiome disruption: Prenatal exposure to glyphosate altered gut bacteria and their function. Bacteria linked to depression, Parkinson’s disease, and metabolic disease increased, along with chemical changes, including excess acetate, which, at high levels, can disturb metabolism and drive nervous system overstimulation.
• Hormonal shifts: Appetite hormones were thrown off balance. Ghrelin (which triggers hunger) was lower, while leptin (which signals fullness) was higher, a pattern seen in obesity and weakened gut barriers. In healthy mice, glyphosate exposure altered the production of key metabolic hormones, potentially linking it to endotoxemia—a potentially hazardous condition where toxins from gut bacteria leak into the bloodstream.
• Gut–brain signals: The herbicide disrupted the normal links between bacteria and key chemicals, such as GLP-1 and tryptophan metabolites, both of which are vital for blood sugar control, mood, and immunity. Strongest effects were seen in the grandchildren. Overall, higher glyphosate exposure was associated with lower GLP-1 levels, suggesting lasting impacts on metabolism and gut-brain signaling across generations.
• Colon barrier weakness: In healthy mice, glyphosate reduced mucus-producing cells, thinning the gut barrier and making it easier for bacteria to cross into tissue and activate the immune system. These effects weren’t seen in colitis-prone mice, whose existing inflammation may have masked them.

In contrast, mice already prone to colitis showed fewer apparent effects from glyphosate, likely because their existing inflammation masked them, the researchers say. They did, however, show signs of gut-related nerve inflammation, the study shows.

“These results show that while the gut microbiome remains largely stable, prenatal glyphosate exposure reconfigures it in ways that may promote inflammation, metabolic dysfunction, and neuroimmune disruption,” the researchers say. “The persistence of these shifts across generations and their emergence at human-relevant doses highlights their potential significance for long-term health.”

To model real-world exposures in this study, researchers provided pregnant mice—both healthy and prone to colitis—with drinking water containing glyphosate at doses based on the average American diet (0.01 mg/kg/day) or the U.S. EPA’s current safety limit (1.75 mg/kg/day).  

The animals underwent behavioral tests, blood sugar and insulin tolerance tests, as well as detailed analyses of their gut tissue. Gut bacteria were examined through DNA sequencing, and blood samples were tested for hormones and metabolites.

The researchers caution that it remains unclear whether the changes are passed down through epigenetics (heritable changes in DNA regulation) or through the gut microbiome. However, the appearance of effects in grandchildren suggests a transgenerational impact. Some results also differed between males and females, suggesting sex-specific pathways.

While the study was exploratory, the consistency of disruptions across metabolism, behavior, and immunity highlights the need for more targeted work, the researchers say. Mice and humans share many of the same genes, but the way those genes are expressed can differ.

The fact that effects appeared at very low doses also suggests glyphosate may not follow a simple “higher dose equals greater harm” pattern. This may make it harder for traditional high-dose safety tests to detect the real risks, the researchers say, raising questions about whether today’s regulations adequately protect public health.

“These findings suggest that prenatal glyphosate exposure, even below regulatory thresholds, may disrupt multiple physiological systems across generations, highlighting the need for further research and potential regulatory consideration,” they say.

Reference

Barnett JA, Josephson JK, Yuzbashian E, et al. Prenatal exposure to dietary levels of glyphosate disrupts metabolic, immune, and behavioral markers across generations in mice. Science of The Total Environment. 2025;1002:180437. doi:10.1016/j.scitotenv.2025.180437