Table 7_Interactions between the intestinal microbiome and host genes in regulating vibriosis resistance in Cynoglossus semilaevis.xlsx

BackgroundChinese 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.
MethodsIn 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. Histopathological sections were conducted to detected the histopathological changes in the posterior intestinal tissues of resistant and susceptible individuals. 16S rRNA sequencing was performed to characterize the changes in intestinal microbial community. RNA-seq was used for the identification of host differentially expressed genes (DEGs). The associations between intestinal microbes and host genes were illustrated by perform an integrated analysis of the differential intestinal microbes and host DEGs.
ResultsObvious 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 analysis indicated that Vibrio increased but Stenotrophomonas, Chryseobacterium, Delftia, and Salinivibrio decreased in the susceptible group. 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.
ConclusionsThe results of this study 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. Strong gene-microbe correlations may imply that the intestinal microbiome may interact with host genes to collectively regulate the vibriosis resistance in Chinese tongue sole, but the causality between them remains unestablished and requires further validation.

背景：半滑舌鳎（Cynoglossus semilaevis）是目前中国广泛养殖的重要商业比目鱼品种。近年来，弧菌病频繁暴发，对半滑舌鳎水产养殖业造成了高死亡率与巨额经济损失。肠道菌群在宿主免疫及抵御病原菌入侵过程中发挥关键作用，但弧菌病背景下肠道菌群与宿主基因的互作机制仍有待深入解析。
方法：本研究选取哈维氏弧菌（Vibrio harveyi）感染7天后的抗病与易感个体，探究其肠道组织病理学、肠道菌群与宿主基因表达的变化，并鉴定宿主基因与菌群的关联。通过组织病理切片检测抗病与易感个体的后肠组织病理变化；采用16S rRNA测序表征肠道微生物群落的组成变化；利用RNA测序（RNA-seq）鉴定宿主差异表达基因（DEGs）；通过整合分析差异肠道菌群与宿主差异表达基因，阐明肠道菌群与宿主基因间的关联。
结果：抗病组与易感组在炎症细胞浸润、黏膜层组织解离等方面存在显著组织病理学差异。16S rRNA测序分析显示，易感组中弧菌属（Vibrio）丰度升高，而寡养单胞菌属（Stenotrophomonas）、金黄杆菌属（Chryseobacterium）、戴沃斯菌属（Delftia）以及盐弧菌属（Salinivibrio）丰度降低。与对照组相比，易感组共检测到1986个差异表达基因（DEGs），数量显著高于抗病组的310个差异表达基因。易感组的差异表达基因显著富集于抗原加工呈递、MHC蛋白复合体、免疫应答等免疫相关GO条目，以及抗原加工呈递、吞噬体、蛋白酶体等免疫相关通路。通过整合分析差异肠道菌群与宿主差异表达基因，共鉴定得到207组强关联的基因-菌群对。
结论：本研究结果表明，哈维氏弧菌（Vibrio harveyi）感染会严重损伤肠道组织，并显著改变肠道菌群组成与宿主基因表达水平，在易感个体中尤为明显。强基因-菌群关联提示肠道菌群或可通过与宿主基因互作，共同调控半滑舌鳎的弧菌病抗病性，但二者间的因果关系尚未明确，仍需进一步验证。