Exposing new taxonomic variation with inflammation - a murine model-specific genome database for gut microbiome researchers.
Exposing new taxonomic variation with inflammation - a murine model-specific genome database for gut microbiome researchers.
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DOI：
10.1186/s40168-023-01529-7
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发表时间：
2023-05-20
期刊：
影响因子：
15.5
通讯作者：
中科院分区：
文献类型：
--
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鼠类 CBA/J 小鼠模型广泛支持免疫学和肠道病原体研究。该模型阐明了沙门氏菌与肠道微生物组的相互作用，因为病原体增殖不需要对天然微生物群进行破坏性预处理，也不会变得系统性，从而类似于人类胃肠炎疾病的进展。尽管对广泛的研究界有价值，但 CBA/J 小鼠的微生物群并未出现在当前的小鼠微生物组基因组目录中。在这里，我们展示了 CBA/J 小鼠肠道微生物组的第一个微生物和病毒基因组目录。利用未经治疗和感染沙门氏菌、高度炎症小鼠的粪便微生物群落，我们进行了基因组重建，以确定对肠道微生物组成员和功能潜力的影响。通过深度全群落测序（~ 42.4 Gbps/样本），我们重建了 2281 个细菌和 4516 个病毒草图基因组。沙门氏菌挑战显着改变了 CBA/J 小鼠的肠道成员资格，揭示了在非炎症小鼠中条件罕见且未采样的 30 属和 98 种。此外，发炎群落中调节宿主抗炎途径的微生物基因被耗尽，而呼吸能量产生的基因则被丰富。我们的研究结果表明，沙门氏菌感染期间丁酸盐浓度的降低与Alistipes成员相对丰度的降低相对应。 CBA/J 微生物基因组与著名的小鼠肠道微生物组数据库的菌株水平比较确定了该资源中新采样的谱系，而与人类肠道微生物组的比较则扩展了主要 CBA/J 抗炎菌株的宿主相关性。该 CBA/J 微生物组数据库首次从这一广泛使用的实验室模型中获取肠道内相关的、未培养的微生物的基因组样本。利用这一资源，我们对沙门氏菌如何重塑完整的小鼠肠道群落提出了功能性、菌株解析的观点，从而超越了先前基于扩增子的方法的推论，推进了病理组学的理解。沙门氏菌引起的炎症抑制了Alistipes和其他主要成员，而乳杆菌和肠球菌等罕见的共生菌则持续存在。在这个炎症梯度中采样的稀有和新物种促进了这种微生物组资源的实用性，有利于 CBA/J 科学界的广泛研究需求，以及那些使用小鼠模型更广泛地了解炎症对肠道微生物组的影响的人们。视频摘要 在线版本包含可在 10.1186/s40168-023-01529-7 获取的补充材料。
The murine CBA/J mouse model widely supports immunology and enteric pathogen research. This model has illuminated Salmonella interactions with the gut microbiome since pathogen proliferation does not require disruptive pretreatment of the native microbiota, nor does it become systemic, thereby representing an analog to gastroenteritis disease progression in humans. Despite the value to broad research communities, microbiota in CBA/J mice are not represented in current murine microbiome genome catalogs. Here we present the first microbial and viral genomic catalog of the CBA/J murine gut microbiome. Using fecal microbial communities from untreated and Salmonella-infected, highly inflamed mice, we performed genomic reconstruction to determine the impacts on gut microbiome membership and functional potential. From high depth whole community sequencing (~ 42.4 Gbps/sample), we reconstructed 2281 bacterial and 4516 viral draft genomes. Salmonella challenge significantly altered gut membership in CBA/J mice, revealing 30 genera and 98 species that were conditionally rare and unsampled in non-inflamed mice. Additionally, inflamed communities were depleted in microbial genes that modulate host anti-inflammatory pathways and enriched in genes for respiratory energy generation. Our findings suggest decreases in butyrate concentrations during Salmonella infection corresponded to reductions in the relative abundance in members of the Alistipes. Strain-level comparison of CBA/J microbial genomes to prominent murine gut microbiome databases identified newly sampled lineages in this resource, while comparisons to human gut microbiomes extended the host relevance of dominant CBA/J inflammation-resistant strains. This CBA/J microbiome database provides the first genomic sampling of relevant, uncultivated microorganisms within the gut from this widely used laboratory model. Using this resource, we curated a functional, strain-resolved view on how Salmonella remodels intact murine gut communities, advancing pathobiome understanding beyond inferences from prior amplicon-based approaches. Salmonella-induced inflammation suppressed Alistipes and other dominant members, while rarer commensals like Lactobacillus and Enterococcus endure. The rare and novel species sampled across this inflammation gradient advance the utility of this microbiome resource to benefit the broad research needs of the CBA/J scientific community, and those using murine models for understanding the impact of inflammation on the gut microbiome more generally. Video Abstract The online version contains supplementary material available at 10.1186/s40168-023-01529-7.
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影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
1.1
作者：
Antoun M;Hattab Y;Akhrass FA;Hamilton LD
通讯作者：
Hamilton LD
影响因子：
7.3
作者：
Ang Z;Ding JL
通讯作者：
Ding JL
影响因子：
15.9
作者：
Walker GT;Raffatellu M
通讯作者：
Raffatellu M
DOI：
10.1073/pnas.1000080107
发表时间：
2011-03-15
影响因子：
11.1
作者：
Caporaso, J. Gregory;Lauber, Christian L.;Knight, Rob
通讯作者：
Knight, Rob