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普拉梭菌(Faecalibacterium prausnitzii)和一种益生元可保护抗生素和艰难梭菌暴露小鼠模型的肠道健康。

Faecalibacterium prausnitzii and a Prebiotic Protect Intestinal Health in a Mouse Model of Antibiotic and Clostridium difficile Exposure.

机构信息

Lerner Research Institute, Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, USA.

Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.

出版信息

JPEN J Parenter Enteral Nutr. 2018 Sep;42(7):1156-1167. doi: 10.1002/jpen.1053. Epub 2018 Jan 31.

Abstract

BACKGROUND

Clostridium difficile (CD) infection (CDI) increases patient morbidity, mortality and healthcare costs. Antibiotic treatment induces gut dysbiosis and is both a major risk factor for CD colonization and treatment of CDI. Probiotics have been trialed to support commensal gut microbiota and reduce CDI. This study investigated commensal microbe Faecalibacterium prausnitzii (FP) and a prebiotic, both known to yield butyrate and be anti-inflammatory and immunomodulatory, on CD colonization and gut integrity in mice.

METHODS

Mice were randomly grouped and supplemented daily with FP, prebiotic, FP + prebiotic, FP/prebiotic supernatant, or saline throughout the entire study. Following treatment with clindamycin for 3 days, mice were exposed to CD. Feces were collected at baseline, the day after antibiotic, and 1, 3, and 5 days after CD exposure and cultured for bacterial overgrowth and CD colonization. On days 1 and 5 after CD exposure, mice were randomly euthanized, and proximal colon was dissected for histological analysis and preparation of RNA for analysis of proinflammatory and anti-inflammatory cytokines.

RESULTS

Although all mice exhibited bacterial overgrowth and CD colonization, bacterial burden resolved quicker in the FP + prebiotic group. This was associated with induction and resolution of innate immune responses, anion exchanger, and tight junction protein preservation in proximal colon. CD toxin virulence potential was questionable as expression of CD toxin B receptor was depleted in the FP + prebiotic group.

CONCLUSION

Supplementation with anti-inflammatory butyrate-supporting commensal bacteria and prebiotic may support innate immune responses and minimize bacterial burden and negative effects during antibiotic and CD exposure.

摘要

背景

艰难梭菌(CD)感染(CDI)会增加患者的发病率、死亡率和医疗保健成本。抗生素治疗会导致肠道菌群失调,是 CD 定植和 CDI 治疗的主要危险因素。益生菌已被尝试用于支持共生肠道微生物群并减少 CDI。本研究调查了共生微生物 Faecalibacterium prausnitzii(FP)和一种益生菌,它们都能产生丁酸,具有抗炎和免疫调节作用,对 CD 定植和小鼠肠道完整性的影响。

方法

小鼠被随机分组,在整个研究过程中每天补充 FP、益生菌、FP+益生菌、FP/益生菌上清液或生理盐水。用克林霉素治疗 3 天后,小鼠接触 CD。在基线、抗生素后第 1 天、接触 CD 后第 1、3 和 5 天收集粪便进行细菌过度生长和 CD 定植培养。在接触 CD 后第 1 和第 5 天,随机处死小鼠,解剖近端结肠进行组织学分析,并准备 RNA 用于分析促炎和抗炎细胞因子。

结果

尽管所有小鼠都出现了细菌过度生长和 CD 定植,但 FP+益生菌组的细菌负荷更快得到解决。这与近端结肠固有免疫反应的诱导和解决、阴离子交换器和紧密连接蛋白的保存有关。CD 毒素的毒力潜力值得怀疑,因为 FP+益生菌组中 CD 毒素 B 受体的表达被耗尽。

结论

补充抗炎丁酸支持的共生细菌和益生菌可能有助于支持固有免疫反应,并在抗生素和 CD 暴露期间最小化细菌负荷和负面影响。

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