Bisphenol A, bisphenol S and their glucuronidated metabolites modulate glycolysis and functional responses of human neutrophils

Bisphenol A (BPA) and its main substitute, bisphenol S (BPS), are synthetic organic compounds found in various consumer products, in particular food and beverage containers. Numerous reports have shown a link between bisphenol exposure, human contamination and increased health problems. BPA, BPS and their metabolites are detectable in bodily fluids (blood, urine) and were reported to affect immune cells and their responses. Though, the impact of those chemicals on neutrophils, the most abundant leukocytes in the circulation, remains poorly described. Therefore, we examined the effects of BPA, BPS and their monoglucuronide conjugates on neutrophil energy metabolism and anti-microbial functions, mainly phagocytosis, superoxide anion generation and CXCL8/IL-8 chemokine production. We observed that short and prolonged exposures of neutrophils to these chemicals modulate the basal and the bacterium-derived peptide N-formyl-methionyl-leucyl-phenylalanine-induced glycolysis, with BPS causing the most alterations. The variation in energy metabolism was not associated with dysfunctions in cell cytotoxicity, phagocytosis, nor superoxide anion production upon exposure to bisphenols. In contrast, bisphenols significantly reduced the production of CXCL8/IL-8 by neutrophils, an effect found to be greater with the glucuronidated metabolites. Our study highlights that BPA, BPS and their glucuronidated metabolites alter the energy metabolism and certain anti-microbial responses of neutrophils, with possible health implications. Importantly, we found that BPS and the glucuronidated metabolites of BPA and BPS showed higher endocrine-disrupting potential than BPA. More studies on bisphenols, especially the less-documented BPS and bisphenol metabolites, are needed to fully determine their risks, allow better regulation of these compounds, and restrict their extensive usage.