Intestinal microbial products from alcohol-fed mice contribute to intestinal permeability and peripheral immune activation.

IF 3.2 3区医学 Q1 Medicine

Alcoholism, clinical and experimental research Pub Date : 2019-09-05 DOI:10.1111/acer.14176

Derrick R. Samuelson, Min Gu, J. Shellito, P. Molina, Christopher M. Taylor, Meng Luo, D. Welsh

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引用次数: 15

Abstract

BACKGROUND Alcohol use causes significant disruption of intestinal microbial communities, yet exactly how these dysbiotic communities interact with the host is unclear. We sought to understand the role of microbial products associated with alcohol-dysbiosis in mice on intestinal permeability and immune activation in an in-vitro model system. METHODS Microbiota samples from binge-on-chronic alcohol-fed and pair-fed male and female mice were cultured in Gifu Anaerobic Broth for 24 hours under anaerobic conditions. Live/whole organisms were removed, microbial products were collected, and added to human peripheral blood mononuclear cells (PBMC) or polarized C2BBe1 intestinal epithelial monolayers. Following stimulation, transepithelial electrical resistance (TEER) was measured using a volt/ohm meter and immune activation of PBMC was assessed via flow cytometry. RESULTS Microbial products from male and female alcohol-fed mice significantly decreased TEER (mean percentage change from baseline alcohol-fed 0.86 Ω/cm2 v. pair-fed 1.10 Ω/cm2 ) compared to microbial products from control mice. Following ex-vivo stimulation immune activation of PBMC was assessed via flow cytometry. We found that microbial products from alcohol-fed mice significantly increased the percentage of CD38+ CD4+ (mean alcohol-fed 17.32%+0.683% SD v. mean pair-fed 14.2%+1.21% SD, P<0.05) and CD8+ (mean alcohol-fed 20.28%+0.88% SD v. mean pair-fed 12.58%+3.59% SD, P<0.05) T-cells. CONCLUSIONS Collectively, these data suggest that microbial products contribute to immune activation and intestinal permeability associated with alcohol dysbiosis. Further, utilization of these ex-vivo microbial product assays will allow us to rapidly assess the impact of microbial products on intestinal permeability and immune activation and to identify probiotic therapies to ameliorate these defects. This article is protected by copyright. All rights reserved.

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酒精喂养小鼠的肠道微生物产物有助于肠道通透性和外周免疫激活。

饮酒会导致肠道微生物群落的严重破坏，但这些益生菌群落如何与宿主相互作用尚不清楚。我们试图在体外模型系统中了解与小鼠酒精生态失调相关的微生物产物对肠道通透性和免疫激活的作用。方法将慢性酒精暴饮暴食和配对饲养的雌雄小鼠的微生物群样本在岐阜市厌氧肉汤中厌氧培养24小时。活的/完整的生物体被去除，微生物产物被收集，并加入到人外周血单核细胞(PBMC)或极化C2BBe1肠上皮单分子层。刺激后，使用伏特/欧姆计测量经上皮电阻(TEER)，并通过流式细胞术评估PBMC的免疫激活。结果与对照组小鼠相比，雄性和雌性酒精喂养小鼠的微生物产物显著降低了TEER(从基线酒精喂养0.86 Ω/cm2到成对喂养1.10 Ω/cm2的平均百分比变化)。体外刺激后，通过流式细胞术评估PBMC的免疫激活。我们发现，酒精喂养小鼠的微生物产物显著提高了CD38+ CD4+(平均酒精喂养17.32%+0.683% SD vs平均配对喂养14.2%+1.21% SD, P<0.05)和CD8+(平均酒精喂养20.28%+0.88% SD vs平均配对喂养12.58%+3.59% SD, P<0.05) t细胞的百分比。综上所述，这些数据表明微生物产物有助于与酒精生态失调相关的免疫激活和肠道通透性。此外，利用这些离体微生物产品检测将使我们能够快速评估微生物产品对肠道通透性和免疫激活的影响，并确定改善这些缺陷的益生菌疗法。这篇文章受版权保护。版权所有。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alcoholism, clinical and experimental research 医学-药物滥用

CiteScore

5.90

自引率

9.40%

发文量

219

审稿时长

1 months

期刊介绍： Alcoholism: Clinical and Experimental Research''s scope spans animal and human clinical research, epidemiological, experimental, policy, and historical research relating to any aspect of alcohol abuse, dependence, or alcoholism. This journal uses a multi-disciplinary approach in its scope of alcoholism, its causes, clinical and animal effect, consequences, patterns, treatments and recovery, predictors and prevention.