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一种孢子形成的益生菌补充剂可改善反复艰难梭菌定植期间小鼠的肠道免疫反应并保护肠道健康。

A Spore-Forming Probiotic Supplement Improves the Intestinal Immune Response and Protects the Intestinal Health During Recurrent Clostridioides difficile Colonization in Mice.

机构信息

Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.

出版信息

JPEN J Parenter Enteral Nutr. 2020 Nov;44(8):1428-1438. doi: 10.1002/jpen.1851. Epub 2020 Jun 4.

Abstract

BACKGROUND

Around 15%-30% of patients develop recurrent Clostridioides difficile infection (CDI) as conventional therapies disrupt protective gut microbiota. We tested if supplementation with a spore-forming probiotic would protect intestinal health in a mouse model of recurrent CD colonization.

METHODS

Methods: Female CF-1 mice were exposed to CD spores (4-log colony-forming units/10 μL) and then randomly assigned to receive either saline (CD-S) or probiotic (CD-PRO). Control mice received only saline (control). Following confirmation of initial CD colonization, mice were treated with vancomycin (10 days). After 5 days, mice recolonized with CD were treated again with vancomycin (10 days) and euthanized 5 days later. Fecal samples were collected at select time points for bacterial analysis. Following euthanasia, blood samples, cecum contents, and the intestine were collected for analysis.

RESULTS

Probiotic supplementation mitigated the antibiotic-induced changes in cecum weight (P < .001). Probiotic-supplemented mice had increased messenger RNA expression of several immune parameters, accompanied by lower serum iron levels compared with CD-S mice (P < .05). Lower expressions of TNF α and calprotectin (P ≤ .05) were observed in CD-PRO mice compared with CD-S. The probiotics also supported the expression of intestinal tight junction proteins, which were diminished in the proximal colon of CD-S mice (P < .05).

CONCLUSION

Mice supplemented with targeted spore-forming probiotics exhibited improved immune responses and nutrition immunity properties, which were linked with less inflammation and enhanced intestinal barrier proteins during recurrent CD colonization.

摘要

背景

由于常规疗法会破坏保护性肠道微生物群,约 15%-30%的患者会出现复发性艰难梭菌感染 (CDI)。我们测试了补充形成孢子的益生菌是否会在复发性 CD 定植的小鼠模型中保护肠道健康。

方法

雌性 CF-1 小鼠暴露于 CD 孢子(4 对数集落形成单位/10 μL),然后随机分配接受生理盐水 (CD-S) 或益生菌 (CD-PRO)。对照小鼠仅接受生理盐水 (对照)。在确认初始 CD 定植后,用万古霉素治疗小鼠(10 天)。5 天后,再次用万古霉素治疗重新定植 CD 的小鼠(10 天),5 天后安乐死。在选定的时间点收集粪便样本进行细菌分析。安乐死后收集血液样本、盲肠内容物和肠道进行分析。

结果

益生菌补充剂减轻了抗生素诱导的盲肠重量变化(P <.001)。与 CD-S 小鼠相比,益生菌补充小鼠的几种免疫参数的信使 RNA 表达增加,血清铁水平降低(P <.05)。与 CD-S 小鼠相比,CD-PRO 小鼠的 TNF α 和钙卫蛋白表达降低(P ≤.05)。益生菌还支持肠道紧密连接蛋白的表达,而在 CD-S 小鼠的近端结肠中这些蛋白的表达减少(P <.05)。

结论

补充靶向形成孢子的益生菌的小鼠表现出改善的免疫反应和营养免疫特性,这与复发性 CD 定植期间炎症减少和增强的肠道屏障蛋白有关。

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