PROJECT SUMMARY
The prevalence of obesity and diabetes continue to rise unabated in the United States,
creating a grave social and economic burden. Although development of these diseases is
multi-faceted and complex, there is accumulating evidence for the impact of environmental
chemical exposures on metabolic homeostasis. Currently, glyphosate is the most commonly
used herbicide in the United States, however, to date, no studies have ever assessed whether
glyphosate exposure impacts the development of obesity and diabetes. Thus, the long-term
goal of this project is to better understand how recent and current pesticide usage can impact
long-term metabolic homeostasis.
Glyphosate targets the shikimate pathway found in plants, and not mammals, leading
to the assumption of its general safety. However, glyphosate can also target bacteria, and
glyphosate exposure results in an altered gut microbiome profile. Despite the fact that
previous pesticides are associated with metabolic disease, and that glyphosate is known to
alter the gut microbiota which can impact energy and glucose homeostasis, no study has ever
examined whether exposure to glyphosate can result in development of obesity and/or
diabetes. One of the main roles of the gut microbiota is bile acid metabolism, and studies
suggest that alterations in bile acid signaling represent a plausible link between the gut
microbiota and regulation of metabolic homeostasis via changes in Farnesoid X receptor
(FXR) signaling. These facts, coupled with our preliminary data, led to the hypothesis that
exposure to glyphosate shifts the gut microbiome, leading to altered intestinal bile acid
signaling that contributes to impairments in energy and glucose homeostasis. This hypothesis
will be tested in 3 aims: 1) assess if exposure to glyphosate during different developmental
timepoints promotes metabolic dysfunction in male and female mice on a chow or high-fat diet,
2) determine the role of the gut microbiome in the effects of glyphosate exposure on metabolic
homeostasis, and 3) identify the impact of altered bile acid signaling via glyphosate exposure
in impaired metabolic homeostasis. The proposed study will be the first ever to provide
mechanistic insight of the effects of glyphosate exposure on metabolic homeostasis. This
proposal will provide valuable data leading to further research examining how environmental
pesticide usage can affect human health, and possibly identify microbial targets to offset the
detrimental effects of environmental chemical use.
