Gnotobiotic zebrafish microbiota display inter-individual variability affecting host physiology.
Gnotobiotic zebrafish microbiota display inter-individual variability affecting host physiology.
复制标题
知生斑马鱼微生物群表现出影响宿主生理机能的个体间变异。
DOI：
10.1101/2023.02.01.526612
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Valm,AlexM
中科院分区：
文献类型：
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作者：
Adade,EmmanuelE;Stevick,RebeccaJ;Pérez-Pascual,David;Ghigo,Jean-Marc;Valm,AlexM
在受控的实验室条件下，用多物种细菌群落重新常规化的非菌生物动物模型通常用于在比常规动物更可重现的条件下研究宿主-微生物群相互作用。然而，这些模型的有用性受限于细菌定殖的动物间变异性以及我们普遍缺乏对微米至毫米尺度的微生物群组装体的个体间波动和时空动态的理解。在这里，我们通过分析肠道定殖效率，细菌组成和宿主肠道粘液生产之间的差异，显示了gnotobiotic模型的低估变异性，常规和gnotobiotic斑马鱼幼虫与9种从常规微生物群中分离的细菌的混合物重新约定。尽管相似的细菌群落组成，我们观察到高度变异性的细菌沿着肠道的空间分布中的重新约定的模型。我们还观察到，虽然细菌丰度和每条鱼的肠粘液不相关，但与传统动物相比，重新常规化的鱼具有较低的肠粘液，这表明粘液产生的刺激取决于微生物群的组成。因此，我们的研究结果表明，可变的殖民表型影响宿主生理学和影响使用gnotobiotic动物的研究中的实验结果的再现性。这项工作提供了深入了解gnotobiotic模型的异质性，并需要准确地评估reconventionalization在宿主微生物群研究的再现性。
Gnotobiotic animal models reconventionalized under controlled laboratory conditions with multi-species bacterial communities are commonly used to study host-microbiota interactions under presumably more reproducible conditions than conventional animals. The usefulness of these models is however limited by inter-animal variability in bacterial colonization and our general lack of understanding of the inter-individual fluctuation and spatio-temporal dynamics of microbiota assemblies at the micron to millimeter scale. Here, we show underreported variability in gnotobiotic models by analyzing differences in gut colonization efficiency, bacterial composition, and host intestinal mucus production between conventional and gnotobiotic zebrafish larvae re-conventionalized with a mix of 9 bacteria isolated from conventional microbiota. Despite similar bacterial community composition, we observed high variability in the spatial distribution of bacteria along the intestinal tract in the reconventionalized model. We also observed that, whereas bacteria abundance and intestinal mucus per fish were not correlated, reconventionalized fish had lower intestinal mucus compared to conventional animals, indicating that the stimulation of mucus production depends on the microbiota composition. Our findings, therefore, suggest that variable colonization phenotypes affect host physiology and impact the reproducibility of experimental outcomes in studies that use gnotobiotic animals. This work provides insights into the heterogeneity of gnotobiotic models and the need to accurately assess re-conventionalization for reproducibility in host-microbiota studies.