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Total body irradiation-induced colon damage is prevented by nitrate-mediated suppression of oxidative stress and homeostasis of the gut microbiome.
Nitric Oxide ( IF 3.2 ) Pub Date : 2020-05-26 , DOI: 10.1016/j.niox.2020.05.002
Weili Wang 1 , Liang Hu 2 , Shimin Chang 3 , Linsha Ma 3 , Xiangchun Li 4 , Zi Yang 5 , Conglin Du 5 , Xingmin Qu 5 , Chunmei Zhang 6 , Songlin Wang 7
Affiliation  

Inorganic dietary nitrate plays vital roles in biological functions via the exogenous NO3-/NO2-/NO pathway under hypoxia and ischemia. We previously verified the antioxidative effects of inorganic nitrate in a mouse model of total body irradiation (TBI). Accordingly, in this study, we evaluated the effects of inorganic nitrate on prevention of TBI-induced colon injury and dysbiosis of the gut microbiome. Nitrate significantly rescued the abnormal biological indexes (body weight, white blood cell, red blood cell, platelet, hemoglobin level and intestinal canal lengths) induced by TBI. Then, we detected oxidative stress and DNA damage indexes (phospho-histone H2AX and p53 binding protein 1), which were both increased by irradiation (IR) and alleviated by nitrate. IR-induced apoptosis and senescence were ameliorated by inorganic nitrate. The distribution of the gut microbiome differed for mice with TBI and those receiving inorganic nitrate. The average abundance of Lactobacillus significantly increased, and that of Bacteroidales decreased at the genus level in the nitrate group compared with that in the IR alone group. At 30 days after TBI, the abundances of Bacteroides and Faecalibaculum decreased, whereas that of Lactobacillus increased in the IR + nitrate group compared with that in the IR alone group. Inorganic nitrate efficiently prevents TBI-induced colon epithelium injury and maintains the homeostasis of the gut microbiome. Thus, our results showed that inorganic nitrate might be a promising treatment for TBI induced colon injury.



中文翻译:

硝酸盐介导的肠道微生物组氧化应激和体内稳态的抑制可防止全身辐射引起的结肠损伤。

无机膳食硝酸盐通过外源NO3起着生物学功能至关重要的作用- / NO2 -/ NO途径在缺氧和缺血下。我们先前验证了全身辐射(TBI)小鼠模型中无机硝酸盐的抗氧化作用。因此,在这项研究中,我们评估了无机硝酸盐对预防TBI引起的结肠损伤和肠道微生物组营养不良的作用。硝酸盐可有效挽救由TBI引起的异常生物学指标(体重,白细胞,红细胞,血小板,血红蛋白水平和肠管长度)。然后,我们检测到氧化应激和DNA损伤指数(磷酸组蛋白H2AX和p53结合蛋白1),它们都通过辐射(IR)升高而被硝酸盐缓解。无机硝酸盐改善了IR诱导的细胞凋亡和衰老。患有TBI的小鼠和接受无机硝酸盐的小鼠肠道微生物组的分布有所不同。与单独IR组相比,硝酸盐组乳酸菌的平均丰度显着增加,而细菌类细菌的平均丰度在属水平上降低。TBI后30天,与单独的IR组相比,IR +硝酸盐组中的细菌和Faecalibaculum的丰度降低,而乳​​酸杆菌的丰度增加。无机硝酸盐可有效防止TBI引起的结肠上皮损伤,并维持肠道微生物组的稳态。因此,我们的结果表明,无机硝酸盐可能是TBI引起的结肠损伤的一种有前途的治疗方法。与单独的IR组相比,IR +硝酸盐组的拟杆菌和Faecalibaculum的丰度降低,而乳​​酸杆菌的丰度增加。无机硝酸盐可有效防止TBI引起的结肠上皮损伤,并维持肠道微生物组的稳态。因此,我们的结果表明,无机硝酸盐可能是TBI引起的结肠损伤的一种有前途的治疗方法。与单独的IR组相比,IR +硝酸盐组的拟杆菌和Faecalibaculum的丰度降低,而乳​​酸杆菌的丰度增加。无机硝酸盐可有效防止TBI引起的结肠上皮损伤,并维持肠道微生物组的稳态。因此,我们的结果表明,无机硝酸盐可能是TBI引起的结肠损伤的一种有前途的治疗方法。

更新日期:2020-05-26
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