Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii.
Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii.
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DOI：
10.3389/fmicb.2016.01520
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发表时间：
2016
影响因子：
5.2
通讯作者：
Wilhelm SW
中科院分区：
文献类型：
--
作者：
Stough JM;Dearth SP;Denny JE;LeCleir GR;Schmidt NW;Campagna SR;Wilhelm SW
C57 BL/6小鼠广泛用于哺乳动物免疫功能和代谢的体内研究。在先前的研究中，观察到当从不同供应商购买的C57 BL/6小鼠感染约氏疟原虫（鼠疟疾的病原体）时，它们表现出不同的免疫反应和显著不同的寄生虫负荷：当肠道内容物移植到gnotobiotic小鼠中时，这些模式是可重复的。为了深入了解耐药机制，我们从两家供应商Taconic Biosciences（低寄生虫血症）和Charles River Laboratories（高寄生虫血症）购买的小鼠中取出整个盲肠，以确定合并的宿主和微生物代谢组和元转录组。除两份Charles River样本外，我们观察到供应商内总体细菌基因表达的相似性≥90%，供应商之间的相似性≤80%。相对于购自Taconic的小鼠，Charles River小鼠中总共有33个细菌基因差异表达（p值< 0.05）。其中，fliC、ureABC和nuo基因家族的六个成员在对更严重的疟疾易感的微生物组中比例过高。此外，38个小鼠基因在这些声称的遗传相同的小鼠中差异表达。差异表达的基因包括basigin，一种恶性疟原虫侵入红细胞所需的细胞表面受体。检测到代谢物库的差异，但其与疟疾感染，微生物群落活动或宿主反应的相关性尚不清楚。我们的数据提供了新的靶点，可能将肠道微生物活性与C57 BL/6模式生物的疟疾抗性和易感性表型联系起来。
C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed ≥90% similarity in overall bacterial gene expression within vendors and ≤80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value < 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism.
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影响因子：
--
作者：
Clasquin, Michelle F;Melamud, Eugene;Rabinowitz, Joshua D
通讯作者：
Rabinowitz, Joshua D
影响因子：
2.5
作者：
Gewirtz, AT
通讯作者：
Gewirtz, AT
影响因子：
2.5
作者：
Green, Maia L.;Singh, Amar V.;Knudsen, Thomas B.
通讯作者：
Knudsen, Thomas B.
影响因子：
3.7
作者：
Hoffmann C;Dollive S;Grunberg S;Chen J;Li H;Wu GD;Lewis JD;Bushman FD
通讯作者：
Bushman FD
DOI：
10.1084/jem.20081398
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jones RB;Ndhlovu LC;Barbour JD;Sheth PM;Jha AR;Long BR;Wong JC;Satkunarajah M;Schweneker M;Chapman JM;Gyenes G;Vali B;Hyrcza MD;Yue FY;Kovacs C;Sassi A;Loutfy M;Halpenny R;Persad D;Spotts G;Hecht FM;Chun TW;McCune JM;Kaul R;Rini JM;Nixon DF;Ostrowski MA
通讯作者：
Ostrowski MA