Reproduction rate and death are important factors in species success in a community. Both reproduction and death rate can be influenced by genetic drift or selective pressures from the environment. Previousin vivo and in vitro studies have shown that Bisphenol A (BPA) exposure impacts microbiome community diversity and functional phenotype of the host. These studies modeled microbiota dynamics in a bioreactor or in animal hosts for 10 or more days and most remarked on a decrease in the Phylum Firmicutes. A recent in vivo experiment demonstrated that quorum sensing mediated by Autoinducer-2 (AI-2) specifically enriched Firmicutes after streptomycin challenge. AI-2 signaling is an important regulator of bacterial growth and is significantly more prevalent in Firmicutes compared to Bacteroidetes, the two primary phyla of the gut. 17β-estradiol, E2, has been shown to inhibit AHL-mediated quorum sensing (Beury-Cirou A 2013).
In this work, the impact of BPA and E2 on AI-2 detection and bacterial physiology was explored. Differential effects of E2 and BPA on growth of various E. coli strains, V. harveyi and Enterococcus faecalis were observed between species and strains tested. Strikingly, a 6 fold increase in growth of V. harveyi was observed when incubated with 100nM E2 compared to no treatment and a linear trend was observed relative to E2 concentration. Significant quenching was observed for both BPA and E2 at physiologically relevant concentrations using a V. harveyi biosensor. The dose-response activity of V. harveyi bioluminescence output in response to synthetic AI-2, E. coli strains, 13 gut strains and feces from healthy male and female humans was also evaluated. Of the 13 gut isolates analyzed, most contained putative genomic luxS produced conditioned media that induced bioluminescence in V. harveyi. Importantly, fecal slurry from male but not the female healthy volunteer induced bioluminescence in V. harveyi. Fecal microbiota dynamics and AI-2 production in a batch fermentation were also explored. In contrast to previous studies, BPA exposed ferments maintained higher diversity of Observed, Shannon, and Chao1 metrics than the Control; however, differences in community structure between 25uM BPA treatment and Control were not significant. In agreement with animal studies, higher abundance of Bacteroides sp was observed in BPA exposure compared to the Control ferment, with significant enrichment of Bacteroides uniformis and Allistipes.
Until now, studies have been limited to how E2 and BPA impact health via mechanisms of the body. These observations support a novel mechanism in which BPA exposure could influence gut microbiota phenotype, possible community composition, and result in a holobiont phenotype through AI-2 disruption. Indeed, there could be an innate role for E2 in regulation of microbiota phenotypes and possibly community composition. Future investigations to explore the gut microbiota as a mediator of endocrine disruption could lead to novel treatments to currently intractable syndromes associated with microbiota and hormone dysregulation.
