Open Collections

Barnett, Jacqueline A.

University of British Columbia

Glyphosate, commonly known as Roundup®, is heavily used in Canada, with over 50 million kilograms purchased annually. Its pre-harvest use results in residues in Canadian food staples, including wheat, legumes, and soy. Glyphosate can stimulate bacterial dysbiosis, which is known to promote inflammatory bowel disease (IBD). Previous studies examining glyphosate have used high doses to elicit an effect and have only explored direct exposure in healthy populations. This study aimed to assess the effects of prenatal glyphosate exposure at physiologically relevant levels on the gut bacteriome and its impact on colitis and associated metabolic and behavioral alterations in colitis-resistant and susceptible animals. Two doses of glyphosate were selected: the acceptable daily intake set by the Environmental Protection Agency (EPA) (1.75 mg/kg/day) and the Average American dose calculated with a registered dietician based on values of glyphosate found in items that make up a North American diet (0.01 mg/kg/day). Breeding pairs of colitis-resistant and colitis-susceptible mice were exposed during pregnancy and two generations of animals were raised. The results revealed that colitis-resistant mice with ancestors exposed to glyphosate developed colitis, characterized by increased histopathological damage, goblet cell depletion and reduced Mucin2 expression within the colon. Additionally, animals in the EPA Upper Limit F2 group exhibited impaired glucose clearance, GLP-1 depletion, and decreased locomotor activity. Colitis-susceptible offspring displayed modest exacerbation of colitis characterized by an increase in macrophages within the submucosa of the EPA Upper Limit F2 group and increased expression of proinflammatory cytokines, including RELMβ, IFNɣ and IL-17a within the Average American Diet and EPA Upper Limit F2 groups. Colitis-resistant and susceptible animals showed taxonomic changes within the colon and changes in serum levels of gut-brain mediators, including reductions in kynurenine within healthy animals and reductions in serum serotonin within colitis-susceptible animals. While both colitis-resistant and colitis-susceptible animals experienced increased colonic inflammation, metabolic changes, and alterations to the gut-brain-microbiome axis, these effects were more pronounced in colitis-resistant animals. The findings of this study require immediate further exploration and consideration of regulatory practices, particularly the use of glyphosate pre-harvest, to mitigate potential health risks.

Text

2024-04-23

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87935

Biochemistry and Molecular Biology

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/