TY - JOUR
T1 - MicroRNA-based host response to toxicant exposure is influenced by the presence of gut microbial populations
AU - Williams, Maggie R.
AU - Stedtfeld, Robert D.
AU - Stedtfeld, Tiffany M.
AU - Crawford, Robert B.
AU - Kuwahara, Tomomi
AU - Kaminski, Norbert E.
AU - Tiedje, James M.
AU - Hashsham, Syed A.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/11/25
Y1 - 2021/11/25
N2 - Segmented filamentous bacteria (SFB) and Bacteroides fragilis are known to interact with the host immune response through the aryl hydrocarbon receptor (Ahr). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental 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 impact of gut microbial members on miRNA expression or its modulation in the presence of an environmental toxicant. 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 μg/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 responses 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.
AB - Segmented filamentous bacteria (SFB) and Bacteroides fragilis are known to interact with the host immune response through the aryl hydrocarbon receptor (Ahr). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental 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 impact of gut microbial members on miRNA expression or its modulation in the presence of an environmental toxicant. 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 μg/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 responses 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.
KW - Gut microbiome
KW - NanoString nCounter
KW - Segmented filamentous bacteria
KW - TCDD
KW - microRNAs
UR - http://www.scopus.com/inward/record.url?scp=85111029670&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2021.149130
DO - 10.1016/j.scitotenv.2021.149130
M3 - Article
AN - SCOPUS:85111029670
SN - 0048-9697
VL - 797
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 149130
ER -
