By Marcella Santiago, Visiting Predoctoral Fellow, Zimmermann Group, EMBL Heidelberg

In today’s world, agrochemicals and plasticizers are ubiquitous, playing critical roles in agriculture and industry. However, their impact on human health, particularly through interactions with gut microbiota, remains underexplored. In our study, we set out to investigate the interaction of the gut microbiome with a selection of pesticides and plasticizers, targeting the biotransformation potential of the gut microbiota for these chemicals.

Expanding the Scope: From Agrochemicals to Plasticizers

Our initial focus was on 30 widely used agrochemicals, but recognizing the opportunity to broaden the scope, we added four more pesticides and 10 plasticizers to the analysis, bringing the total to 44 compounds. The selection of pesticides comprise well-known fungicides, insecticides and herbicides, all of which are commonly applied in agriculture. These are a major component of the human exposome threatening human health through direct exposure of the chemicals by agricultural work and through exposure following the food chain reaching parts of human population that are geographically distant from the agricultural production sites.

Plasticizers, on the other hand, are commonly used to enhance the flexibility of plastics and are of significant concern due to their toxicological relevance, particularly as endocrine disruptors. The plasticizers included in this study can be categorized into two groups: traditional plasticizers and plasticizer substitutes. The substitutes were developed as alternatives to traditional plasticizers in response to growing concerns about their environmental and health impacts. However, similar to the traditional plasticizers, these substitutes have also been identified as potentially harmful, particularly because of their disruptive eLects on the endocrine system. Despite their widespread use, research on how these chemicals interact with the gut microbiome remains limited. By including both pesticides and plasticizers in our analysis, we aimed to address this critical knowledge gap.

Gut Microbial Metabolism

We pooled compounds to incubate them with a human fecal microbial community under controlled anaerobic culture conditions to test compound biotransformation. Samples were collected over 24 hours to track changes in compound levels, employing LC-MS analysis. A standout finding was the significant degradation of pyraclostrobin by the fecal microbiota. This result suggests that certain agrochemicals may be particularly susceptible to microbial transformation, a process that could have implications for both their efficacy and toxicity.

What’s Next?

The next step will involve testing the same compounds with fecal communities from humans, rats, and mice to explore how gut microbial communities from different host species biotransform these substances. Given its apparent vulnerability to gut microbial degradation, we are also especially interested in further investigating pyraclostrobin. This is a widely used fungicide, known for its broad-spectrum efficacy against

fungal diseases in crops, being mainly used in cereals, grapes and vegetables, being approved for use in both the European Union and Brazil. The eLect of pyraclostrobin on the gut microbiota of mammals has not been widely explored in the literature, nor has the impact of the gut microbiota on the metabolism of pyraclostrobin. These future studies will aim to uncover the specific microbial pathways and mechanisms responsible for its biotransformation.