Activation of the Aryl Hydrocarbon Receptor Modulates the Gut Microbiome

Open Access
Author:
Nichols, Robert Gordon
Area of Honors:
Interdisciplinary in Immunology and Infectious Disease and Toxicology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Andrew Patterson, Thesis Supervisor
  • Pamela Hankey, Honors Advisor
  • Gary H Perdew, Faculty Reader
Keywords:
  • Toxicology
  • Aryl Hydrocarbon Receptor
  • microbiome
  • microbiota
Abstract:
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental concern. It is extremely persistent so it can stay in the environment for a long time. TCDD binds the aryl hydrocarbon receptor and causes many different effects including cytochrome p450 activation, induction of phase two detoxifying enzymes and immune cell regulation. Many of these effects are associated with inflammation and inflammatory signaling. The gut microbiome is an integral part of normal physiology and regulates many different processes like complete food digestion, protection from harmful bacteria, insulin sensation, satiety, and even obesity prevention. The gut can also have a large role on inflammation, either attenuating it or inducing it. In this study, I explored the idea that TCDD affects the gut microbiome and this can lead to a state of inflammation. We used cecal DNA which was then sequenced at the Penn State Genomics Facility with 16S rRNA gene specific primers. The sequenced 16S rRNA was then analyzed on a terminal-based software called Mothur to obtain taxonomic data. The taxonomic data was then used to quantitatively and qualitatively determine if certain species increased or decreased after treatment with 2,3,7,8-tetrachlorodibenzofuran (TCDF). TCDF was used because it is a less toxic and more rapidly cleared chemical compared to TCDD. Overall 2 major phyla, a family and a species were examined: Bacteriodetes increased after treatment, Firmicutes decreased after treatment, Clostridia decreased after treatment and Oscillibactor decreased after treatment. Along with an analysis of the major results, an in-depth guide of 16S rRNA gene analysis is discussed.