A Humanized Diet Profile May Facilitate Colonization and Immune Stimulation in Human Microbiota-Colonized Mice
A Humanized Diet Profile May Facilitate Colonization and Immune Stimulation in Human Microbiota-Colonized Mice
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DOI：
10.3389/fmicb.2020.01336
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发表时间：
2020-06-19
影响因子：
5.2
通讯作者：
Hansen, Axel K.
中科院分区：
文献类型：
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作者：
Moreno-Indias, Isabel;Lundberg, Randi;Hansen, Axel K.
背景尽管使用无菌小鼠用于人类粪便转移的重要性，但与小鼠微生物群接种相比，对小鼠中人类微生物群接种后的定殖效率和免疫刺激的研究很少。我们测试了在用人类（HM）或小鼠微生物群（MM）接种亲本一代后再繁殖一代的小鼠中的定殖效率和免疫应答。此外，我们测试了是否可以通过饮食方法改善HM-定殖小鼠中的定殖效率和免疫刺激：如果这些小鼠被喂食更接近人类饮食的饮食，无论是在其动物脂肪和蛋白质的来源[“动物来源”（AS）饮食]还是在其来自小鼠饮食的正常来源的常量营养素的比例[“人类概况”（HP）饮食]。结果虽然在具有人类微生物群的小鼠中显著较低（30-40%对61-70%），但在喂食HP饮食的HM小鼠（40%）和喂食AS的MM小鼠（70%）中的定殖效率显著较高。喂食HP的小鼠的微生物群与喂食标准啮齿动物食物的小鼠的微生物群相当，而喂食动物源饮食（AS）的小鼠的微生物群单独聚集。与人类微生物群接种的小鼠相比，接种小鼠粪便的小鼠具有显著更多的CD 4（+）T细胞和Cd 4表达，显著更少的调节性T细胞（TcR）和FoxP 3表达，但细胞比例差异在喂食AS饮食的小鼠之间最为明显。喂食HP饮食的小鼠具有显著更高的Cd 8a表达。结论得出的结论是，具有人源化特征的饮食可以支持在小鼠中建立人微生物群，然而，与接种小鼠微生物群的小鼠相比，这仍然会引起较低的定殖效率。
Background In spite of the importance of the use of gnotobiotic mice for human fecal transfer, colonization efficiency and immune stimulation after human microbiota inoculation in mice are poorly studied compared to mouse microbiota inoculation. We tested the colonization efficiency and immune responses in mice bred for one additional generation after inoculating the parent generation with either a human (HM) or a mouse microbiota (MM). Furthermore, we tested if colonization efficiency and immune stimulation could be improved in HM-colonized mice by dietary approaches: if these were fed a diet closer to the human diet either in its sources of animal fat and protein [the "animal source" (AS) diet] or in its proportions of macronutrients from the normal sources of a mouse diet [the "human profile" (HP) diet]. Results Although significantly lower in mice with a human microbiota (30-40% vs. 61-70%) the colonization efficiency was significantly higher in HM mice fed the HP diet (40%), and in MM mice fed AS (70%). The microbiota of mice fed HP was comparable to the microbiota of mice fed a standard rodent chow, while the microbiota of mice fed the animal source diet (AS) clustered separately. Mice inoculated with mouse fecal matter had significantly more CD4(+)T cells andCd4expression and significantly fewer regulatory T cells (Tregs) andFoxP3expression than human microbiota inoculated mice, but cell proportions differences were mostly apparent between mice fed the AS diet. Mice fed the HP diet had significantly higher expression ofCd8a. Conclusion It is concluded that a diet with a humanized profile could support the establishment of a human microbiota in mice, which will, however, still elicit a lower colonization efficiency compared to mice inoculated with a mouse microbiota.