Thoene-Reineke Christa, Fischer André, Friese Christian, Briesemeister Dana, Göbel Ulf B, Kammertoens Thomas, Bereswill Stefan, Heimesaat Markus M
Forschungseinrichtung für Experimentelle Medizin, Charité - University Medicine Berlin, Berlin, Germany.
Department of Micro-biology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
PLoS One. 2014 Nov 17;9(11):e113406. doi: 10.1371/journal.pone.0113406. eCollection 2014.
Abundance of commensals constituting the intestinal microbiota (IM) affects the immune system and predisposes to a variety of diseases, including intestinal infections, cancer, inflammatory and metabolic disorders. Housing conditions determine the IM and can hence influence the immune system. We analyzed how both variables affect the IM of four immune-compromized mouse lines kept under different housing conditions.
METHODOLOGY/PRINCIPAL FINDINGS: We investigated the IM composition in mice by quantitative 16S rRNA RT-PCR analysis of the main fecal bacterial groups (Enterobacteriaceae, enterococci, lactobacilli, bifidobacteria, Bacteroides/Prevotella (BP) spp., Clostridium leptum and coccoides groups). Mice were homozygous (HO) or heterozygous (HE) for a targeted inactivating mutation of either the IFN-γ Receptor (R), IFN-γ, Rag1 or IL-4 genes. Overall, differences in IM composition were subtle. However, in the SPF-barrier, total eubacterial loads were higher in Rag1 HE versus Rag1 HO mice as well as in IFN-γR HE versus IFN-γR HO and WT animals. Although absent in WT mice, bifidobacterial loads were higher in HO and HE IFN-γ and Rag1 as well as IL-4 HO mice. Furthermore, BP was slightly lower in HO and HE IFN-γR and IFN-γ mice as well as in IL-4 HO mice as compared to WT controls. Interestingly, IM compositions were comparable in WT mice when kept in individual ventilated cages (IVC) or open cages (OC). IFN-γ HO and HE mice, however, had higher enterobacteria and BP loads, but lacked bifidobacteria when kept in OC versus IVC, as was the case in HO and HE Rag1 mice. In addition, Rag1 HO mice harbored higher clostridial loads when housed in OC as compared to IVC. Unexpectedly, lactobacilli levels were higher in IFN-γR mice when kept in OC versus IVC.
CONCLUSION/SIGNIFICANCE: Housing-dependent and immune-deficiency mediated changes in intestinal microbiota composition were rather subtle but may nevertheless impact immunopathology in experimental models.
构成肠道微生物群（IM）的共生菌数量会影响免疫系统，并使人易患多种疾病，包括肠道感染、癌症、炎症和代谢紊乱。饲养条件决定了肠道微生物群，因此可能影响免疫系统。我们分析了这两个变量如何影响饲养在不同条件下的四种免疫缺陷小鼠品系的肠道微生物群。
方法/主要发现：我们通过对主要粪便细菌类群（肠杆菌科、肠球菌、乳酸菌、双歧杆菌、拟杆菌/普雷沃菌属（BP）、纤细梭菌属和球形梭菌属）进行定量16S rRNA RT-PCR分析，研究了小鼠肠道微生物群组成。小鼠为干扰素γ受体（R）、干扰素γ、Rag1或白细胞介素4基因靶向失活突变的纯合子（HO）或杂合子（HE）。总体而言，肠道微生物群组成的差异很细微。然而，在无特定病原体屏障环境中，Rag1杂合子小鼠的总真细菌负荷高于Rag1纯合子小鼠，干扰素γR杂合子小鼠以及干扰素γR杂合子小鼠和野生型动物的总真细菌负荷也更高。双歧杆菌负荷在野生型小鼠中不存在，但在干扰素γ、Rag1以及白细胞介素4纯合子小鼠的纯合子和杂合子中较高。此外与野生型对照相比，干扰素γR、干扰素γ纯合子和杂合子小鼠以及白细胞介素4纯合子小鼠中的BP略低。有趣的是野生型小鼠饲养在独立通风笼（IVC）或开放笼（OC）中时，其肠道微生物群组成具有可比性。然而干扰素γ纯合子和杂合子小鼠饲养在开放笼中时，肠杆菌和BP负荷较高，但缺乏双歧杆菌饲养在独立通风笼中时也是如此，Rag1纯合子和杂合子小鼠也是如此。此外Rag1纯合子小鼠饲养在开放笼中时梭菌负荷高于独立通风笼。出乎意料的是，干扰素γR小鼠饲养在开放笼中时乳酸菌水平高于独立通风笼。
结论/意义：肠道微生物群组成中依赖饲养条件和免疫缺陷介导的变化相当细微，但仍可能影响实验模型中的免疫病理学。
