Gossypol,
the main antinutritional factor in cottonseed protein
concentrate (CPC), could affect the growth conditions of fish, but
the underlying mechanism remains unclear. In this study, an 8-week
feeding trial was carried out to investigate the effects of gossypol
on Nile tilapia (Oreochromis niloticus). Three experimental
diets were designed, including control diet (CON), control diet supplemented
with 150 mg/kg gossypol (ML), and 300 mg/kg gossypol (MH). 16S rRNA
gene sequencing showed that gossypol significantly reduced the richness
and diversity of the gut microbiota. Untargeted metabolite analysis
revealed that most metabolites were down-regulated by gossypol, and
riboflavin was the key metabolite with significant difference between
CON-treated and gossypol-treated groups. Gossypol caused intestinal
inflammation, oxidative stress, and apoptosis. Through fecal bacteria
transplantation experiments, we demonstrated that intestinal microbiota
mediated gossypol-induced negative effects, suggesting that intestinal
microbiota and its metabolite may account for the harmful effects
of gossypol.