Young fecal transplantation modulates the visual toxicity of perfluorobutanesulfonate in aged zebrafish recipients

Abstract

Perfluorobutanesulfonate (PFBS) is an emerging pollutant of potent toxicity to impair visual system. Previous studies highlighted the applicability of gut microbiota manipulation to mitigate the toxicities of PFBS. However, it remains unknown whether transplantation of whole fecal microbiota to PFBS-disturbed gut can restore the health of the recipient animals, especially for aged fish that are of high susceptibility. In the present study, aged zebrafish of 3 years old were first transplanted with feces from young counterparts and then exposed to environmentally relevant concentrations of PFBS. After exposure, toxic effects of PFBS on visual system of aged zebrafish were elucidated based on transcriptional, proteomic, biochemical, histological, and behavioral evidences. In addition, interaction between young fecal transplant and innate visual toxicity of PFBS was further explored in the aged. The results showed that PFBS singular exposure induced lipid peroxidation (by 1.9-fold) in aged male eyes, which were alleviated by young fecal transplantation. PFBS also disturbed the retinal structure of the aged, which was characterized by increases in plexiform layers, but decreases in ganglion neuron number (by 26.8% and 26.0% in males and females, respectively) and optic nerve width (by 14.1% and 12.7% in males and females, respectively). It was unexpected that young fecal transplant was very potent in re-organizing the histological assembly of aged eyes regardless of PFBS coexposure, underlining the intimate interplay between gut and retina. Proteomic profiling provided more clues about the visual toxicology mechanism of PFBS, which was found to typically interfere with synaptic neurotransmission occurring in plexiform layers. However, proteome perturbation of aged eyes by PFBS exposure was effectively shifted by the transplantation of young feces towards the control phenotype, suggesting the high ameliorative potential of young fecal transplantation along the gut-retina axis. Overall, the present study pinpoints the potent visual toxicity of PFBS in aged animals and highlights the efficacy of young fecal transplant to regulate the inherent toxicity of PFBS. Future studies are necessitated to sequence the gut microbiota and unveil the underlying interactive routes between gut microbes and visual system.

Keywords: Aging; PFBS; Proteome; Visual toxicity; Young fecal transplantation; Zebrafish.