Dysregulation of Intestinal Health by Environmental Pollutants: Involvement of the Estrogen Receptor and Aryl Hydrocarbon Receptor.

To determine how environmental pollutants induce dysbiosis of the gut microbiota, we exposed adult zebrafish to model pollutants with varied modes of action (atrazine, estradiol, polychlorinated biphenyl [PCB]126, and PCB153) for 7 days. Subsequently, metagenomic sequencing of the intestines was performed to compare the gut microbiomes among the groups. We observed clear compound- and sex-specific responses to xenobiotic stress. Principal component analysis revealed involvement of the aryl hydrocarbon receptor (AhR) and, to a lesser extent, the estrogen receptor (ER) in the dysregulation of the intestinal microbiota. The model pollutants differentially impaired intestinal and hepatic physiological activities, as indicated by assessments of gut motility, epithelial permeability, inflammation, and oxidative stress. Correlation analysis showed that abnormal Aeromonas reproduction, especially in the PCB126 groups, was significantly positively associated with oxidative damage. Aeromonas closely interacted with Mannheimia and Blastococcus to regulate intestinal permeability. In summary, we demonstrated that ER and AhR signaling regulated the dynamics of the gut microbiota. Our findings provide new mechanistic insight into the complex interactions between the host metabolism and gut microbiota, which may contribute to the grouped assessment of environmental pollutants in future.

Acute exposure to PBDEs at an environmentally realistic concentration causes abrupt changes in the gut microbiota and host health of zebrafish.

Contamination from lower brominated PBDEs is ubiquitous in the environments. However, their effects on gut microbiota and intestinal health have not yet been investigated. This study exposed adult zebrafish to an environmentally realistic concentration of pentaBDE mixture (DE-71) at 5.0 ng/L for 7 days, after which metagenomic sequencing of the intestinal microbiome was conducted and host physiological activities in the intestine and liver were also examined. The results showed that acute exposure to DE-71 significantly shifted the gut microbial community in a sex-specific manner. Certain genera (e.g., Mycoplasma, Ruminiclostridium, unclassified Firmicutes sensu stricto, and Fusobacterium) disappeared from the DE-71-exposed intestines, resulting in decreased bacterial diversity. Bacterial metabolic functions in guts were also affected by DE-71, namely those covering energy metabolism, virulence, respiration, cell division, cell signaling, and stress response. In addition, measurement of diverse sensitive biomarkers showed that the health of male intestines was remarkably compromised by the DE-71 exposure, as indicated by the disruption to its neural signaling (serotonin), epithelial barrier integrity (tight junction protein 2), inflammatory response (interleukin 1ß), oxidative stress and antioxidant capacity, as well as detoxifying potential (ethoxyresorufin-O-deethylase activity). However, female intestines maintained intact physiological activities. Compared to the direct impact on intestines, a latent effect of DE-71 was observed in livers. Co-occurrence network analysis demonstrated that the gut bacteria vigorously interacted to establish the fittest community under DE-71 stress by promoting the reproduction of favorable genera, while diminishing the survival of unfavorable ones. Significant correlations between the zebrafish gut microbiota and physiological activities (e.g., oxidative stress, detoxification, neurotransmission, and epithelial integrity) were also observed. Overall, this study has demonstrated, for the first time, the high susceptibility of gut microbiota and intestinal health of zebrafish to DE-71, thus warranting more work to reveal its mode of toxicity.