Gut microbiota-mediated ferroptosis contributes to mercury exposure-induced brain injury in common carp
Yue Zhang, Peijun Zhang, Yuehong Li
Abstract
Mercury is a heavy metal, which causes irreversible toxicity to fish and is found in aquatic environments around the world. The purpose of this study was to investigate the relative mechanism of mercury exposure on brain injury in common carp. The results showed that mercury exposure could induce brain injury and memory loss in common carp. Meanwhile, mercury exposure could induce neuronal ferroptosis. The ferroptosis inhibitor ferrostatin-1 attenuated mercury-induced brain injury. However, in an in vitro study, mercury did not induce ferroptosis, and ferrostatin-1 did not attenuate mercury-induced common carp brain cell death. Therefore, we speculated that mercury exposure-induced ferroptosis might occur through other pathways. Studies have shown that the gut microbiota contributes to the pathological process of heavy metal-induced injury. Therefore, we detected the effects of mercury exposure on the gut microbiota composition. The results showed that the composition and diversity of the gut microbiota were affected by mercury chloride. Surprisingly, we found that the abundance of Aeromonas, one of the most important pathogenic bacteria of fish, increased significantly. Subsequently, we isolated Aeromonas hydrophila from mercury-exposed carp and these bacteria could lead to brain injury and ferroptosis in common carp. These results suggested that mercury exposure-induced brain injury partly by increasing intestinal A. hydrophila, which led to ferroptosis in common carp.