Intestinal Microbiota Mediates Gossypol-Induced Intestinal Inflammation, Oxidative Stress, and Apoptosis in Fish

Abstract

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.

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“…The intensive search for more affordable protein sources in fish nutrition in aquaculture led to the use of cottonseed protein concentrate, a product with excellent nutritional qualities, except for the existence of gossypol, a sesquiterpene aldehyde, toxic at accumulated high levels. The existence of gossypol causes intestinal inflammatory problems, as has been demonstrated in Nile tilapias, grass carps, and turbots, also in cattle acts as a cardiac and reproductive toxicant [ 69 ]. Perhaps, only ruminant microflora appears to have the ability to inactivate the presence of gossypol in feed [ 70 ].…”