最近,越来越多的证据支持一些复杂的疾病不是归因于给定的病原体,而是宿主肠道微生物群(IM)的生态失调。整个肠道生态系统的改变,而不是单一的病原体,与白色粪便综合征(WFS)有关,一种全球严重的非传染性虾病,而没有实验证据来探索因果关系。在这里,我们进行了全面的宏基因组和代谢组学分析,和肠道微生物移植(IMT),以探讨IM菌群失调与WFS之间的因果关系。
与对照虾相比,我们发现WFS虾中微生物的丰富度和多样性急剧下降。十个属,如弧菌,念珠菌,光细菌,和气单胞菌,在WFS中任职人数过多,而11属,包括Shewanella,几微杆菌,和红杆菌属在对照中富集。这些种群的不同变化可能有助于观察到WFS中赋予硫辛酸代谢和矿物质吸收的途径的下降。同时,一些代谢物,尤其是脂类和有机酸,被发现与WFS中的IM改变有关。结合了多组学和IMT,我们证明了群落组成的显著变化,功能电位,IM的代谢产物与虾WFS密切相关。通过饲料补充攻击验证了归因于IM菌群失调的杰出代谢物。在WFS微生物群落组装中,同质选择和异质选择过程均不太明显。值得注意的是,来自WFS捐赠者的IMT虾最终发展出WFS临床症状,而在受体虾中可以重新表征生态失调IM。
集体,我们的发现为IM菌群失调和虾WFS之间的因果关系提供了确凿的证据,这体现了科赫的微生态假设(肠道微生物群生态失调,一种疾病)在疾病病因中,并从生态学的角度启发我们对病因学的思考。视频摘要。
Recently, increasing evidence supports that some complex diseases are not attributed to a given pathogen, but dysbiosis in the host intestinal microbiota (IM). The full intestinal ecosystem alterations, rather than a single pathogen, are associated with white feces syndrome (WFS), a globally severe non-infectious shrimp disease, while no experimental evidence to explore the causality. Herein, we conducted comprehensive metagenomic and metabolomic analysis, and intestinal microbiota transplantation (IMT) to investigate the causal relationship between IM dysbiosis and WFS.
Compared to the Control shrimp, we found dramatically decreased microbial richness and diversity in WFS shrimp. Ten genera, such as Vibrio, Candidatus Bacilloplasma, Photobacterium, and Aeromonas, were overrepresented in WFS, whereas 11 genera, including Shewanella, Chitinibacter, and Rhodobacter were enriched in control. The divergent changes in these populations might contribute the observation that a decline of pathways conferring lipoic acid metabolism and mineral absorption in WFS. Meanwhile, some sorts of metabolites, especially lipids and organic acids, were found to be related to the IM alteration in WFS. Integrated with multiomics and IMT, we demonstrated that significant alterations in the community composition, functional potentials, and metabolites of IM were closely linked to shrimp WFS. The distinguished metabolites which were attributed to the IM dysbiosis were validated by feed-supplementary challenge. Both homogenous selection and heterogeneous selection process were less pronounced in WFS microbial community assembly. Notably, IMT shrimp from WFS donors eventually developed WFS clinical signs, while the dysbiotic IM can be recharacterized in recipient shrimp.
Collectively, our findings offer solid evidence of the causality between IM dysbiosis and shrimp WFS, which exemplify the \'microecological Koch\'s postulates\' (an intestinal microbiota dysbiosis, a disease) in disease etiology, and inspire our cogitation on etiology from an ecological perspective. Video abstract.