Identifying the effects of pesticides on intestinal permeability and gut-bacterial dysbiosis

If you are interested in a project theme that affects us all and to conduct work of global significance, then look no further! The human gastrointestinal tract is inhabited by a large collection of microorganisms (bacteria, fungi, viruses, small eukaryotes) collectively known as the “microbiome”, which can have a symbiotic or pathogenic relationship with the human host. Changes in human gut microbiota have a role in the aetiology of a large range of clinical conditions such as metabolic syndrome, type 2 diabetes, cancer and obesity as well as behavioural problems (ADHD, autism, depression, psychosis). In addition, gut microbiome imbalance (“dysbiosis”) can compromise gut wall (epithelial) integrity, which is essential for health with “leaky gut” leading to disease including food allergies and intolerances (e.g. non-celiac gluten sensitivity). Gut microbiome status and integrity can be affected by exposure to environmental chemicals such as pesticides[1]. The exposure to pesticides acting as antibiotics, or fungicides, could generate a stable selection pressure on some microbial communities in the human gut microbiome. The aim of this project is to investigate whether pesticides can bring about gut microbiome dysbiosis and compromise gut integrity. Overall, this project will provide insight as to whether pesticides commonly found in human food compromise gut well-being, which can lead to serious ill-health.

Experimental Plan
In this project we propose to study the effects of pesticides that are most frequently found in foodstuffs on human gastrointestinal function. The project will initially focus on glyphosate, the world’s most widely used herbicide, which inhibits the shikimate pathway in plants leading to their death. It is proposed (patent no: US 7,771,736 B2) that glyphosate can act as an antibiotic by inhibiting the same shikimate biochemical pathway in microorganisms compromising their viability. We have recently proven that may indeed be the case where we showed that glyphosate causes alterations in the rat gut microbiome by inhibiting the shikimate pathway [2]. A number of cell tissue culture systems and a range of molecular analytical methods (such as transcriptomics, DNA methylation profiling, metabolomics, genotoxicity) will be used to investigate effects on intestinal function, structure, and permeability, as well as its effects on the gut bacterial microbiome leading to gut dysbiosis and consequent ill-health.

Ultimately, the objective of this study is to provide evidence that will result in improved regulation of pesticides in the food chain leading to better protection of public health.