Intestinal microbiota are considered a sensor for molecular pathways, which orchestrate energy balance, immune responses, and cell regeneration. We previously reported that microbiota restriction promoted higher levels of systemic radiation-induced genotoxicity, proliferative lymphocyte activation, and apoptotic polarization of metabolic pathways. Restricted intestinal microbiota (RM) that harbors increased abundance of Lactobacillus johnsonii (LBJ) has been investigated for bacterial communities that correlated radiation-induced genotoxicity. Indicator phylotypes were more abundant in RM mice and increased in prevalence after whole body irradiation in conventional microbiota (CM) mice, while none of the same ten most abundant phylotypes were different in abundance between CM mice before and after heavy ion irradiation. Muribaculum intestinale was detected highest in female small intestines in RM mice, which were lacking Ureaplasma felinum compared with males, and thus these bacteria could be contributing to the differential amounts of radiation-induced systemic genotoxicity between the CM and RM groups. Helicobacter rodentium and M.intestinale were found in colons in the radiation-resistant CM phenotype. While the expression of interferon-γ was elevated in the small intestine, and lower in blood in CM mice, high-linear energy transfer radiation reduced transforming growth factor-β with peripheral interleukin (IL)-17 in RM mice, particularly in females. We found that female RM mice showed improved micro-architectural bone structure and anti-inflammatory radiation response compared with CM mice at a delayed phase 6 weeks postexposure to particle radiation. However, microbiota restriction reduced inflammatory markers of tumor necrosis factor in marrow, when IL-17 was reduced by intraperitoneal injection of IL-17 neutralizing antibody.

译文

:肠道菌群被认为是分子途径的传感器,可以协调能量平衡,免疫反应和细胞再生。我们以前曾报道过,微生物群的限制促进了更高水平的全身辐射诱导的遗传毒性,增殖性淋巴细胞活化以及代谢途径的凋亡极化。对于与辐射诱导的基因毒性相关的细菌群落,已经研究了含有增加的约翰逊乳杆菌(LBJ)丰富度的限制性肠道菌群(RM)。在常规微生物区系(CM)小鼠中,RM小鼠中的指示剂系统型更为丰富,并且在全身照射后患病率增加,而在重离子照射之前和之后,这十种最丰富的系统型在CM小鼠之间的丰度没有任何不同。在RM小鼠的雌性小肠中,鼠毛肠菌的检出率最高,与雄性相比,这些小鼠缺乏猫尿素原体,因此这些细菌可能导致CM组和RM组之间辐射诱导的全身性基因毒性的差异。在抗辐射的CM表型的结肠中发现了啮齿类杆菌和肠杆菌。在CM小鼠中,干扰素-γ的表达在小肠中升高,而在血液中则更低,而高线性能量转移辐射则在RM小鼠中降低了转化生长因子-β的表达,而外周血白介素(IL)-17尤其在雌性小鼠中。我们发现,在暴露于粒子辐射后6周的延迟阶段,与CM小鼠相比,雌性RM小鼠显示出改善的微结构骨骼结构和抗炎辐射反应。然而,当通过腹膜内注射IL-17中和抗体降低IL-17时,微生物群限制降低了骨髓中肿瘤坏死因子的炎症标志物。

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