Digestive issues are still on the rise, but gluten alone is not the major culprit. So does glyphosate affect the gut microbiome?

Digestive disorders are increasing in parallel with the “Westernization” of our lifestyle and agricultural practices

Gastrointestinal disorders with an inflammatory component have increased in parallel with the “Westernization” of our diet and lifestyle. However, most digestive disorders are non-specific and difficult to diagnose based on objective medical criteria and reliable biomarkers.

Among the contributing factors, diet can play an important role, with gluten being one of the culprits. Indeed, the number of people without a celiac disease diagnosis who avoid gluten has dramatically increased over the past decade and is attributed to the fact that excluding wheat is seen as a healthy dietary pattern. However, scientists have shown that gluten alone is not responsible for intestinal and extra-intestinal symptoms in healthy individuals without celiac disease.

Potential triggers in wheat that may account for symptoms in people with wheat sensitivity include wheat-germ agglutinin, FODMAPs and amylase trypsin inhibitors. Recently, the herbicide glyphosate applied to dry wheat crops, making it easier to harvest them, has also received considerable attention with regards to digestive and overall health.

One mechanism by which glyphosate might influence human health involves changes in gut microbiome composition

Although glyphosate has been considered largely to be non-toxic to humans, given that it does not have the capacity to affect the metabolic pathways of mammalian cells, recent laboratory and animal studies have shown both the potential direct toxicity of glyphosate and its indirect detrimental effects on the gut microbiome.

The shikimate pathway enzyme EPSPS, which is inhibited by glyphosate, is found in all plants and bacteria and is involved in amino acid, hormone and vitamin synthesis. While commensal bacteria are more sensitive to glyphosate, opportunistic pathogens such as Escherichia coli and Staphylococcus aureus have developed mutations that minimize its harmful effect. Although the direct toxicity of glyphosate has been considered when setting acceptable daily intake levels, its subtle effects on the gut microbiome have not, which means glyphosate’s influence on health may have been underestimated. For instance, grain and legume-based products can contain glyphosate residues, which can be over the maximum limit currently set for cereal crops.

Animal and human studies suggest that exposure to glyphosate and herbicide adjuvants can induce adverse health outcomes mediated by the microbiome

Animal and human studies suggest that chronic exposure to glyphosate-based herbicides can induce adverse health outcomes. In particular, urinary excretion of glyphosate and its metabolite aminomethylphosphonic acid was shown to have increased between 1993 and 2016.

Some evidence exists—mainly in bees and rats—about the secondary effects of glyphosate on health (even when used at doses considered safe) through promoting opportunistic pathogens and extinguishing commensal bacteria such as Lactobacillus species and butyrate-producing bacteria.

The consequences of glyphosate-induced changes in the gut microbiome composition may, for example, include altered gut microbial development during early life and increased anxiety and depression-like behaviors in mice. Furthermore, microbiome alterations similar to the ones observed with glyphosate were shown to be associated with other systemic manifestations that include inflammation, reflux disease, obesity, colon cancer and celiac disease.

Although some of the glyphosate-led changes in the gut microbiome resemble those observed in celiac disease and intestinal inflammatory conditions, it is too early to infer how the changes in gut microbiota composition translate into human health. Beyond wheat, glyphosate can be found in other dietary sources such as legumes, corn and soy. In addition, additives used in conjunction with glyphosate in herbicides can also drive changes in the gut microbiome. However, it should be acknowledged that the level and quality of evidence that supports glyphosate’s effects on the microbiome is weak and some research in rats suggests glyphosate has only a limited impact on the gut microbiome.

Next steps to consider when exploring glyphosate’s impact on gut and overall health

In the light of those background findings, glyphosate’s effect on the gastrointestinal milieu and gut microbiota should be considered when updating safety recommendations in the near future. Findings indicate that exposure to glyphosate is not completely safe and some countries have issued statements of intention to ban or restrict pesticides and herbicides including glyphosate.

Future studies on the relationships between chronic glyphosate exposure and human health are needed, which consider a wide range of doses (not only limited to high doses), taking into account other components in herbicides that might be involved in the effects on health outcomes and including in studies non-healthy populations susceptible to environmental triggers.

References:

Catassi C, Alaedini A, Bojarski C, et al. The overlapping area of non-celiac gluten sensitivity (NCGS) and wheat-sensitive irritable bowel syndrome (IBS): an update. Nutrients. 2017; 9(11):1268. doi: 10.3390/nu9111268.

Barnett JA, Gibson DL. Separating the empirical wheat from the pseudoscientific chaff: a critical review of the literature surrounding glyphosate, dysbiosis and wheat-sensitivity. Front Microbiol. 2020; 11:556729. doi: 10.3389/fmicb.2020.556729.

Myers JP, Antoniou MN, Blumberg B, et al. Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environ Health. 2016; 15:19. doi: 10.1186/s12940-016-0117-0.

Mills PJ, Kania-Korwel I, Fagan J, et al. Excretion of the herbicide glyphosate in older adults between 1993 and 2016. JAMA. 2017; 318(16):1610-1611. doi: 10.1001/jama.2017.11726.

Agostini LP, Dettogni RS, Dos Reis RS, et al. Effects of glyphosate exposure on human health: insights from epidemiological and in vitro studies. Sci Total Environ. 2020; 705:135808. doi: 10.1016/j.scitotenv.2019.135808.