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在炎症性肠病的多药耐药1a缺陷小鼠模型中,接种肠球菌不会影响结肠炎症。

Inoculation with enterococci does not affect colon inflammation in the multi-drug resistance 1a-deficient mouse model of IBD.

作者信息

Barnett Matthew P G, Dommels Yvonne E M, Butts Christine A, Zhu Shuotun, McNabb Warren C, Roy Nicole C

机构信息

Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch, Palmerston North, 4474, New Zealand.

Gravida: National Centre for Growth and Development, Private Bag 92019, Auckland, 1142, New Zealand.

出版信息

BMC Gastroenterol. 2016 Mar 3;16:31. doi: 10.1186/s12876-016-0447-y.

Abstract

BACKGROUND

Intestinal bacteria are thought to play a role in the pathogenesis of human inflammatory bowel disease (IBD). We investigated whether oral inoculation with specific intestinal bacteria increased colon inflammation in the multi-drug resistance 1a-deficient (Mdr1a (-/-) ) mouse model of IBD.

METHODS

Five-week-old Mdr1a (-/-) mice (FVB background) and FVB mice were randomly assigned to one of two treatment groups (Control or Inoculation, n = 12 per group). All mice were fed AIN-76A rodent diet, and mice in the Inoculation groups also received a single oral bacterial inoculation consisting of twelve cultured Enterococcus species combined with conventional intestinal flora obtained from the gastrointestinal tract of healthy mice (EF.CIF). Body weight, food intake, and disease activity index (DAI) were assessed throughout the study, and at 21 or 24 weeks of age, inflammation was assessed post-mortem by determining colon length and histological injury score (HIS), and plasma serum amyloid A (SAA).

RESULTS

Mdr1a (-/-) mice consumed more food than FVB mice at 13 weeks of age (P < 0.05). There was also a significant effect of genotype on body weight, with Mdr1a (-/-) mice weighing less than FVB mice throughout the study (P < 0.05) regardless of treatment, but there was no effect of inoculation on body weight (P > 0.25). Colon HIS of Mdr1a (-/-) mice was significantly higher than that of FVB mice in the Control (9.3 ± 4.7 (mean ± SD) vs. 0.58 ± 0.51; P < 0.001) and Inoculation (6.7 ± 5.1 vs. 0.92 ± 0.39; P < 0.001) groups. There was no difference in colon HIS of Mdr1a (-/-) mice in the Control group compared with Mdr1a (-/-) mice in the Inoculation group (P = 0.25), nor was there any difference in within-group variation of colon HIS in these two Mdr1a (-/-) groups. DAI was higher in Mdr1a (-/-) mice than in FVB mice, but there was no effect of treatment in either strain, nor were there any differences in colon length or plasma SAA.

CONCLUSIONS

Inoculation of Mdr1a (-/-) mice with the EF.CIF inoculum described here does not increase colon inflammation or reduce the observed variability of inflammation.

摘要

背景

肠道细菌被认为在人类炎症性肠病(IBD)的发病机制中起作用。我们研究了在IBD的多药耐药1a缺陷(Mdr1a (-/-))小鼠模型中,口服特定肠道细菌是否会加重结肠炎症。

方法

将5周龄的Mdr1a (-/-)小鼠(FVB背景)和FVB小鼠随机分为两个治疗组之一(对照组或接种组,每组n = 12)。所有小鼠均喂食AIN-76A啮齿动物饲料,接种组的小鼠还接受了一次口服细菌接种,该接种由12种培养的肠球菌与从健康小鼠胃肠道获得的传统肠道菌群(EF.CIF)组成。在整个研究过程中评估体重、食物摄入量和疾病活动指数(DAI),并在21或24周龄时,通过测定结肠长度、组织学损伤评分(HIS)和血浆血清淀粉样蛋白A(SAA)对炎症进行死后评估。

结果

13周龄时,Mdr1a (-/-)小鼠比FVB小鼠消耗更多食物(P < 0.05)。基因型对体重也有显著影响,在整个研究过程中,无论治疗如何,Mdr1a (-/-)小鼠的体重均低于FVB小鼠(P < 0.05),但接种对体重没有影响(P > 0.25)。在对照组(9.3 ± 4.7(平均值±标准差)对0.58 ± 0.51;P < 0.001)和接种组(6.7 ± 5.1对0.92 ± 0.39;P < 0.001)中,Mdr1a (-/-)小鼠的结肠HIS显著高于FVB小鼠。对照组的Mdr1a (-/-)小鼠与接种组的Mdr1a (-/-)小鼠在结肠HIS方面没有差异(P = 0.25),这两个Mdr1a (-/-)组在结肠HIS的组内变异方面也没有差异。Mdr1a (-/-)小鼠的DAI高于FVB小鼠,但两种品系的治疗均无效果,结肠长度或血浆SAA也没有差异。

结论

用此处描述的EF.CIF接种物接种Mdr1a (-/-)小鼠不会增加结肠炎症或降低观察到的炎症变异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc6/4778357/4045510ee6c2/12876_2016_447_Fig3_HTML.jpg

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