Interactions between the intestinal microbiome and host genes in regulating vibriosis resistance in Cynoglossus semilaevis

Weiwei Zheng¹Yadong Chen¹Tao Yang¹Zhihong Liu¹Dong Xu¹Huizong Han²Yaning Wang¹Xiaoqing Xi³Tengteng Wang^2*Songlin Chen^1*

• ¹Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences (CAFS), Qingdao, China
• ²Shandong Marine Resource and Environment Research Institute, Yantai, China
• ³Rongcheng Marine Economic Development Center, Weihai, China

Chinese tongue sole (Cynoglossus semilaevis) is now a commercially important flatfish species widely farmed in China. In recent years, frequent outbreak of vibriosis has caused high mortality rates and enormous economic losses to the aquaculture industry of Chinese tongue sole. The intestinal microbiome plays a crucial role in host immunity and protection against pathogen invasion. However, the interactions between the intestinal microbiome and host genes in vibriosis remain poorly understood. In this study, we investigated the changes in intestinal histopathology, intestinal microbiome and host gene expression in resistant and susceptible individuals at 7 days post infection with Vibrio harveyi, and identified the host gene-microbe correlations. Obvious histopathological differences were observed between the resistant and susceptible groups in terms of inflammatory cells infiltration, and tissue dissociation of mucosal layer. 16S rRNA sequencing was performed to characterize the changes in intestinal microbial community, in which Vibrio increased but Stenotrophomonas, Chryseobacterium, Delftia, and Salinivibrio decreased in the susceptible group. RNA-seq analysis indicated that compared to the control group, 1,986 differentially expressed genes (DEGs) were detected in the susceptible group, significantly more than the 310 DEGs found in the resistant group. DEGs in the susceptible group were significantly enriched in immune-related GO terms, such as antigen processing and presentation, MHC protein complex, and immune response, and pathways, including antigen processing and presentation, phagosome, and proteasome. Through an integrative analysis of differential intestinal microbes and host DEGs, 207 strong gene-microbe correlations were identified, but the causality between microbes and host genes remians unestablished and requires further validation. These findings indicate that V. harveyi infection severely damages the intestinal tissue and substantially alters the composition of intestinal microbiome and the expression of host genes, especially in susceptible individuals. Meanwhile, the intestinal microbiome may interact with host genes to collectively regulate the vibriosis resistance in Chinese tongue sole.