Bisphenol S exposure induces intestinal inflammation: An integrated metabolomic and transcriptomic study

As a typical substitute for bisphenol A (BPA), bisphenol S (BPS) is raising concerns due to the potential adverse effects on human health. Limit evidence is available to understand the toxicity of BPS to the digestive system, especially for intestine. In this study, we aimed to investigate the potential effects and underlying mechanisms of BPS exposure on human colon mucosal epithelial cells (NCM460). Our results showed that BPS exposure significantly increased the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-17A (IL-17A). The tight junctions of the cells has been destroyed by BPS exposure, which was characterized by a down-regulation of the tight junction proteins (Claudin1 and zonula occluden 1 (ZO1)). A multi-omics study explored the underlying mechanisms based on the metabolomic and transcriptomic responses. A variety of neurotransmitters increased significantly after exposure to BPS. The top enriched pathway was "glutamatergic synapse", which was activated by BPS exposure, resulting in the up-regulation of l-glutamine. Links were observed among the altered metabolites, genes and cytokines. Our results indicate that exposure to BPS may disturb the balance of gut-brain axis, leading to the production of inflammatory cytokines and the destruction of tight junction in NCM460 cells. It provides new clue for the development of intestinal inflammation in terms of the environmental pollutants.