Activation of aryl hydrocarbon receptor by dioxin directly shifts gut microbiota in zebrafish

Environ Pollut. 2019 Dec;255(Pt 3):113357. doi: 10.1016/j.envpol.2019.113357. Epub 2019 Oct 7.


Gut microbiota is of critical importance to host health. Aryl hydrocarbon receptor (AhR) is found to be closely involved in the regulation of gut microbial dynamics. However, it is still not clear how AhR signaling shapes the gut microbiota. In the present study, adult zebrafish were acutely exposed to an AhR antagonist (CH223191), an AhR agonist (polychlorinated biphenyl 126; PCB126) or their combination for 7 d. Overall intestinal health and gut microbial community were temporally monitored (1 d, 3 d and 7 d) and inter-compared among different groups. The results showed that single exposure to PCB126 significantly disrupted the overall health of intestines (i.e., neural signaling, inflammation, epithelial barrier integrity, oxidative stress). However, CH223191 failed to inhibit but enhanced the physiological toxicities of PCB126, implying the involvement of extra mechanisms rather than AhR in the regulation of intestinal physiological activities. Dysbiosis of gut microbiota was also caused by PCB126 over time as a function of sex. It is intriguing that CH223191 successfully abolished the holistic effects of dioxin on gut microbiota, which inferred that growth of gut microbes was directly controlled by AhR activation without the involvement of host feedback modulation. When coming to detailed alterations at certain taxon, both antagonistic and synergistic interactions existed between CH223191 and dioxin, depending on fish sex, exposure duration and bacterial species. Correlation analysis found that gut inflammation was positively associated with pathogenic Legionella bacteria, but was negatively associated with epithelial barrier integrity, suggesting that integral intestinal epithelial barrier can prevent the influx of pathogenic bacteria to induce inflammatory response. Overall, this study has deciphered, for the first time, the direct regulative effects of AhR activity on gut microbiota. Future research is warranted to elucidate the specific mechanisms of AhR action on certain bacterial population.

Keywords: Aryl hydrocarbon receptor; CH223191; Gut microbiota; PCB126; Zebrafish intestinal health.

MeSH terms

  • Animals
  • Bacteria / metabolism
  • Basic Helix-Loop-Helix Transcription Factors
  • Dioxins / toxicity*
  • Dysbiosis
  • Gastrointestinal Microbiome / drug effects*
  • Intestines
  • Microbiota
  • Polychlorinated Biphenyls
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon / metabolism
  • Signal Transduction
  • Zebrafish / metabolism


  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Dioxins
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Polychlorinated Biphenyls
  • 3,4,5,3',4'-pentachlorobiphenyl