Gut microbiota combined with metabolome dissects Fluorene-9-bisphenol exposure-induced male reproductive toxicity.

A major alternative to bisphenol A (BPA), fluorene-9-bisphenol (BHPF) has been shown to cause multiorgan toxicity. However, its reproductive toxicity and the underlying biological mechanism remain largely unknown. Recently, changes in the gut microbiota and metablome caused by environmental contaminant exposure and their potential impact on male reproductive health have been of great concern. Therefore, we aimed to elucidate the underlying mechanism of BHPF-related fertility impairment by integrating metabolome and microbiome analysis. In the present study, we showed that BHPF exposure caused testicular dysfunction with impaired spermatogenesis and disrupted steroid hormone synthesis. Mechanistically, altered gut microbiota and metabolites were revealed by 16S rDNA sequencing and untargeted metabolomics analysis. Subsequent multi-omics combination analysis revealed a strong correlation between altered microbiota and lipid metabolites. We also found a strong relationship between lipid metabolites and sperm parameters such as sperm concentration, sperm motility, etc. Most importantly, these findings provide new insights into the mechanistic scenario underlying BHPF-induced fertility toxicity, that disrupted lipid metabolism caused by gut microbiota dysbiosis may be a reason for reproductive impairment caused by BHPF exposure.