Superfund Research Program
Gut Microbiome - Host Interactions in Response to TCDD Exposure
Project Leader: Syed A. Hashsham
Grant Number: P42ES004911
Funding Period: 2013-2021
- Project Summary
Final Progress Reports
The work with miRNA carried out as part of this project highlights the importance of the gut microbiome-host communication through miRNAs following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and is the first study to assess the combined differential miRNA expression response to both an environmental toxicant and the association of members of the gut microbiome. Previously the research team demonstrated that gut bacteria modulate host immune markers (T-cells) in response to TCDD exposure. Genes that responded to TCDD in the presence of SFB did not show a significant response in the absence of SFB, and vice versa (Stedtfeld 2017a). Measurement of regulatory T-cells measured in collaboration with the TCDD Impedes the Minimal Activation Threshold Required for Initiation of B Cell Differentiation: An Integrated Experimental and Computational Modeling Approach Project, indicated that they were less impacted by TCDD in SFB-colonized mice (Stedtfeld 2017b). In collaboration with Pacific Northwest National Lab (PNNL), the research team demonstrated that the observations made at the mRNA and microRNA level are replicated at the proteome and metabolome level. In collaboration with the TCDD Impedes the Minimal Activation Threshold Required for Initiation of B Cell Differentiation: An Integrated Experimental and Computational Modeling Approach Project and the Geochemical Controls on the Sorption, Bioavailability, Formation, and Long-term Environmental Fate of Polychlorinated Dibenzo-p-Dioxins (PCDDs) Project, the team examined the bioavailability of TCDD sequestered to activated carbon (AC) on the transcriptomic response of SFB and gut microbiota. The expression of genes associated with SFB significantly increased with TCDD but no change was observed when TCDD was sequestered by AC (Stedtfeld 2017c). This conclusion was further confirmed using metabolomic analysis of the fecal pellets. Using traditional C57BL/6 mice with modified gut microbiomes using environmental doses of antibiotics, the team demonstrated that microbiota perturbed by antibiotics had a greater imbalance of regulatory T-cells in response to dioxin-like compounds (2,3,4,7,9-PeCDF, and 2,3,7,8-TCDF).