Toxic impact of Karenia mikimotoi on intestinal barrier disruption and aggravated the infection response to Vibrio parahaemolyticus in zebrafish larvae.

Karenia mikimotoi, a known bloom-forming dinoflagellate, severely impacts aquatic organisms globally, causing economic losses to the aquaculture industry. Short-term exposure to K. mikimotoi cells has been shown to induce hemolytic toxicity, neurotoxicity, and even mortality in fish. However, the long-term events of K. mikimotoi blooms occur frequently, but its chronic toxicity effects remain unclear. The intestine is the main defense barrier of the fish against algal threats. Herein, zebrafish (Danio rerio) larvae were employed to investigate the toxicity of the ruptured cell solution (RCS) of K. mikimotoi to the intestine. The RCS at an equivalent bloom-relevant abundance was exposed to the zebrafish larvae (8 dpf) for 30 days. The variations in oxidative stress, inflammatory and immune responses, barrier permeability, pathological damage, and intestinal microbiota were evaluated. K. mikimotoi disrupted the oxidation-antioxidation system, damaged the intestinal villi, and decreased the levels of intestinal diamine oxidase activity and D-lactic acid. Moreover, the compositions of intestinal microbiota were altered, with the abundance of Proteobacteria and Firmicutes increased, while Cyanobacteria and Actinobacteria decreased. Furthermore, the immune defense of zebrafish (under the stress of K. mikimotoi) was evaluated by subjecting it to a 24-h infection with Vibrio parahaemolyticus. The zebrafish larvae infected with V. parahaemolyticus after pre-exposure to the RCS of K. mikimotoi demonstrated serious intestinal pathological and immune response changes compared to those infected solely with V. parahaemolyticus. Overall, the results showed the RCS of K. mikimotoi can disrupt the intestinal barrier of zebrafish larvae, thereby aggravating the infection response to the pathogen. This work reveals the chronic toxicity of K. mikimotoi, highlighting the importance of long-term ecological risk assessment of harmful algal bloom.