# Benzophenone-3 remodels gut microbiota diet-dependently to exacerbate non-alcoholic fatty liver disease in zebrafish

## TL;DR

Benzophenone-3, when combined with a high-fat diet, worsens liver disease in zebrafish by disrupting gut bacteria and increasing inflammation.

## Contribution

The study reveals a diet-dependent mechanism by which BP3 interacts with gut microbiota to exacerbate non-alcoholic fatty liver disease.

## Key findings

- Co-exposure to BP3 and a high-fat diet increased liver fat and oxidative damage in zebrafish.
- BP3 altered gut microbiota composition, reducing Bacteroidota and increasing Proteobacteria.
- BP3 effects on gut bacteria varied depending on the diet, highlighting diet-dependent toxicity.

## Abstract

Benzophenone-3 (BP3), a prevalent organic UV filter found in aquatic environments and human tissues, poses potential metabolic risks. This study investigated the combined effects of BP3 (10 μg/L) and a high-fat diet (HFD, 24% crude fat) on non-alcoholic fatty liver disease (NAFLD) development in zebrafish, focusing on gut-liver axis disruption via microbiota. Co-exposure to BP3 and HFD significantly worsened hepatic steatosis, as evidenced by increased triglyceride levels, lipid droplets accumulation, and oxidative damage (elevated hepatic MDA levels and decreased hepatic CAT activity). Additionally, this combined exposure induced gut dysbiosis characterized by a marked decrease in Bacteroidota and Fusobacteriota, along with increased proportions of Proteobacteria and Actinobacteriota, and an altered Firmicutes/Bacteroidota ratio. This dysbiosis compromised intestinal barrier integrity, leading to anterior/middle intestines villus atrophy, endotoxin translocation, and hepatic inflammatory activation. Notably, BP3 demonstrated a diet-dependent effects, depleting Bacteroidia under normal diet while increasing Gammaproteobacteria under HFD. These findings, highlight that BP3 synergizes with HFD to disrupt the microbiota-gut-liver axis, accelerating NAFLD progression, and emphasize the host’s metabolic status as a critical determinant of pollutant-microbiota interactions and toxicity. This diet-dependent effect challenges isolated toxins risk assessments, underscoring the need to incorporate dietary context into NAFLD prevention and environmental health rules.