Microrna-Based Host Response To Toxicant Exposure Is Influenced By The Presence Of Gut Microbial Populations

Segmented filamentous bacteria (SFB) and Bacteroides fragilis are known to interact with the host immune re-sponse through the aryl hydrocarbon receptor (Ahr). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environ-mental toxicant and a high-affinity Ahr ligand has the potential to modify the effect of SFB and B. fragilis. MicroRNAs (miRNA) with their role in regulating gene expression post-transcriptionally, may potentially be used to observe such interactions between SFB, B. fragilis, and TCDD. However, little is known regarding the im-pact of gut microbial members on miRNA expression or its modulation in the presence of an environmental tox-icant. This information is important in understanding toxicant-mediated dysbiosis in gut microbiome and the resulting human health impacts. In this study, C57BL/6 germ-free (GF) mice were colonized with SFB and B. fragilis and administered 30 mu g/kg TCDD every 4 d for 28 d and miRNA were measured. Compared to GF mice, colonization with SFB resulted in an increase in up-and down-regulated Ileal miRNAs. TCDD treatment of this group decreased the number of upregulated miRNA and increased the number of down-regulated miRNAs. Association with SFB and B. fragilis together had a similar but less pronounced effect in response to TCDD treatment. TCDD treatment of GF mice had no miRNA expression response. Immune and inflammatory re-sponses and T-cell differentiation were the key functions impacted by these miRNAs. Overall, these results reveal that the host response to toxicants may also depend on the presence of specific gut microbial populations. (c) 2021 Elsevier B.V. All rights reserved.