Significant alterations of intestinal symbiotic microbiota induced by intraperitoneal vaccination mediate changes in intestinal metabolism of NEW Genetically Improved Farmed Tilapia (NEW GIFT, Oreochromis niloticus)
Authors: Wu Zhenbing , Zhang Qianqian , Yang Jicheng , Zhang Jinyong , Fu Jie , Dang Chenyuan , Liu Mansen , Wang Shuyi , Lin Yaoyao , Hao Jingwen , Weng Meiqi , Xie Derong , Li Aihua 
Published: December 2022

Abstract
Background
After millions of years of coevolution, symbiotic microbiota has become an integral part of the host and plays an important role in host immunity, metabolism, and health. Vaccination, as an effective means of preventing infectious diseases, has been playing a vital role in the prevention and control of human and animal diseases for decades. However, so far, minimal is known about the effect of vaccination on fish symbiotic microbiota, especially mucosal microbiota, and its correlation with intestinal metabolism remains unclear.

Methods
Here we reported the effect of an inactivated bivalent Aeromonas hydrophila/Aeromonas veronii vaccine on the symbiotic microbiota and its correlation with the intestinal metabolism of farmed adult Nile tilapia (Oreochromis niloticus) by 16S rRNA gene high-throughput sequencing and gas chromatography-mass spectrometry metabolomics.

Results
Results showed that vaccination significantly changed the structure, composition, and predictive function of intestinal mucosal microbiota but did not significantly affect the symbiotic microbiota of other sites including gill mucosae, stomach contents, and stomach mucosae. Moreover, vaccination significantly reduced the relative abundance values of potential opportunistic pathogens such as Aeromonas, Escherichia–Shigella, and Acinetobacter in intestinal mucosae. Combined with the enhancement of immune function after vaccination, inactivated bivalent Aeromonas vaccination had a protective effect against the intestinal pathogen infection of tilapia. In addition, the metabolite differential analysis showed that vaccination significantly increased the concentrations of carbohydrate-related metabolites such as lactic acid, succinic acid, and gluconic acid but significantly decreased the concentrations of multiple lipid-related metabolites in tilapia intestines. Vaccination affected the intestinal metabolism of tilapia, which was further verified by the predictive function of intestinal microbiota. Furthermore, the correlation analyses showed that most of the intestinal differential microorganisms were significantly correlated with intestinal differential metabolites after vaccination, confirming that the effect of vaccination on intestinal metabolism was closely related to the intestinal microbiota.

Conclusions
In conclusion, this paper revealed the microbial and metabolic responses induced by inactivated vaccination, suggesting that intestinal microbiota might mediate the effect of vaccination on the intestinal metabolism of tilapia. It expanded the novel understanding of vaccine protective mechanisms from microbial and metabolic perspectives, providing important implications for the potential influence of vaccination on human intestinal microbiota and metabolism.