High-Throughput Screening of Human Gut Bacteria Response to PFAS Exposure

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental chemicals widely used in industrial and consumer products due to their unique chemical and physical properties. Human exposure to PFAS is nearly unavoidable, with these persistent chemicals accumulating in the body and potentially contributing to adverse health outcomes, including cancer and metabolic disorders.

Microbes play essential roles in maintaining our ecosystem balance, acting as decomposers, mutualists, food sources, chemical engineers, and pathogens. While there has been significant interest in understanding the toxicity of PFAS on host tissues (e.g. liver), recent studies indicate that environmental chemicals including PFAS may also impact health by directly or indirectly altering the gut microbiome.

Mapping these effects on the gut microbiome offers new opportunities to explore the mechanisms of microbial toxicity from environmental chemicals and their disruption of host-microbiome interactions. In this proposal, we aim to investigate how PFAS affect the gut microbiome and host-microbiome interactions using a combination of high-throughput screening and in vivo approaches.

First, we will employ a high-throughput optical density (OD) screening platform integrated with robotic automation to assess the effects of three common and nine new kinds of PFAS compounds on over 500 genome-sequenced bacterial isolates and fecal microbial communities from 20 human donors, all conducted in vitro within an anaerobic chamber.

Second, we will evaluate the impact of these disruptions on host-microbiome interactions by transplanting PFAS-sensitive and PFAS-resistant bacterial strains or human fecal communities identified in the first aim into germ-free mice, followed by PFAS exposure.

Our pilot studies involving a screening of 96 bacterial species have already demonstrated that bacterial species exhibit varying sensitivities to PFAS exposure, supporting both the technical feasibility of our proposed research and validating our methodological approach. Our labs are equipped with a well-established anaerobic chamber system and a collection of 500 identified bacterial strains, ensuring that essential resources are readily available. Additionally, our collaboration with the Penn State Gnotobiotic Facility strengthens the feasibility of this project.