BACKGROUND 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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微生态科赫的假设表明，肠道菌群失调是虾白粪综合征的原因。

背景技术近来，越来越多的证据支持一些复杂的疾病不归因于给定的病原体，而是宿主肠道菌群（IM）中的营养不良。肠道生态系统的完整变化，而不是单一病原体，与白色粪便综合征（WFS）有关，白粪综合征是一种全球性严重的非传染性虾病，但没有实验证据可以探讨其因果关系。在这里，我们进行了全面的宏基因组学和代谢组学分析，以及肠道菌群移植（IMT），以研究IM病和WFS之间的因果关系。结果与对照虾相比，我们发现WFS虾的微生物丰富度和多样性大大降低。十个属，例如弧菌，芽孢杆菌，光杆菌和气单胞菌，在WFS中占过多，而11个属，包括希瓦氏菌，Chitinibacter和Rhodobacter在内的对照均富集。这些人群的差异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减少。同时，发现某些代谢物，特别是脂质和有机酸，与WFS中的IM改变有关。结合多组学和IMT，我们证明IM的群落组成，功能潜力和代谢产物的重大改变与虾的WFS密切相关。饲料补充攻击验证了归因于IM代谢异常的杰出代谢物。在WFS微生物群落装配中，同质选择和异质选择过程均较不明显。值得注意的是 来自WFS供体的IMT虾最终发展出WFS临床体征，而致病性IM可以在受体虾中重新表征。结论总体而言，我们的发现为IM病菌病和虾WFS之间的因果关系提供了有力的证据，这证明了病因病原学中的“微生态科赫假设”（一种肠道菌群病，一种疾病），并从生态学角度激发了我们对病因学的认识。录像摘要。并从生态学角度激发我们对病因学的认识。录像摘要。并从生态学角度激发我们对病因学的认识。录像摘要。