Abstract
Environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR), are known to induce host toxicity and structural shifts in the gut microbiota. Key bacterial populations with similar or opposing functional responses to AhR ligand exposure may potentially help regulate expression of genes associated with immune dysfunction. To examine this question and the mechanisms for AhR ligand-induced bacterial shifts, C57BL/6 gnotobiotic mice were colonized with and without segmented filamentous bacteria (SFB) – an immune activator. Mice were also colonized with polysaccharide A producing Bacteroides fragilis – an immune suppressor to serve as a commensal background. Following colonization, mice were administered TCDD (30 μg/kg) every 4 days for 28 days by oral gavage. Quantified with the nCounter® mouse immunology panel, opposing responses in ileal gene expression (e.g., genes associated with T-cell differentiation via the class II major histocompatibility complex) as a result of TCDD dosing and SFB colonization were observed. Genes that responded to TCDD in the presence of SFB did not show a significant response in the absence of SFB, and vice versa. Regulatory T-cells examined in the mesenteric lymph-nodes, spleen, and blood were also less impacted by TCDD in mice colonized with SFB. TCDD-induced shifts in abundance of SFB and B. fragilis compared with previous studies in mice with a traditional gut microbiome. With regard to the mouse model colonized with individual populations, results indicate that TCDD-induced host response was significantly modulated by the presence of SFB in the gut microbiome, providing insight into therapeutic potential between AhR ligands and key commensals.
Highlights
Dysbiosis of certain key immune modulating commensals can influence host disposition to disease and environmental exposure (Snedeker and Hay, 2012)
Comparisons were made between groups of mice (Supplementary Figure S1) that remained uncolonized (UC), mice mono-colonized with B. fragilis (B), mice mono-colonized with segmented filamentous bacteria (SFB) (SFB), and mice co-colonized with both bacteria (SFB+B) to examine: (i) influence of TCDD in presence of SFB (SFB+B, Figure 1A) and (ii) influence of TCDD in absence of SFB (UC and B. fragilis groups, Figure 1B)
The influence of SFB colonization was determined by comparing vehicle dosed SFB+B vs B groups; and the influence of B. fragilis was determined by comparing vehicle dosed UC vs B groups
Summary
Dysbiosis of certain key immune modulating commensals can influence host disposition to disease and environmental exposure (Snedeker and Hay, 2012). Multiple immune activating strains isolated from mice and human stool including segmented filamentous bacteria (SFB) induce Th17 cells in animal studies (Gaboriau-Routhiau et al, 2009; Ivanov et al, 2009; Atarashi et al, 2015; Tan et al, 2016). Bacteria such as Bacteroides fragilis promote the expression of Treg cells through polysaccharide A (PSA) production (Troy and Kasper, 2010). Imbalanced levels of T-cells can influence protection against pathogens or autoimmune diseases (Fantini et al, 2007; Peck and Mellins, 2010)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.