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一种新型革兰氏阴性细菌亚种的免疫调节及肠道形态功能方面

Immunomodulation and Intestinal Morpho-Functional Aspects of a Novel Gram-Negative Bacterium subsp. .

作者信息

Yahfoufi Nour, Alsadi Nawal, Mallet Jean Francois, Kulshreshtha Garima, Hincke Maxwell, Ismail Nafissa, Matar Chantal

机构信息

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.

Department of Innovation in Medical education, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.

出版信息

Front Microbiol. 2021 Jun 22;12:569119. doi: 10.3389/fmicb.2021.569119. eCollection 2021.

DOI:10.3389/fmicb.2021.569119
PMID:34239502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8258396/
Abstract

A novel bacterium ( subsp. ) isolated from the microbiota of wild blueberry fruit was investigated for its immunomodulation capabilities and intestinal morpho-functional aspects. The whole-genome shotgun sequencing of this bacterium led to its new taxonomy and showed absence of pathogenicity genes. Although the bacterium was used for blueberry-fermentation and enhancing its anti-inflammatory effects on neurodegeneration, diabetes, and cancer, no study has assessed the effect of the bacterium on health. In this study, we used several and assays to evaluate the interaction of subsp. with the intestinal mucosa and its impact on the localized immune response. The strain antibiotic susceptibility has been investigated as well as its tolerance to gastric and intestinal environment and ability to attach to human intestinal epithelial cells (Caco-2 and HT-29). In addition, Balb/c mice were used to explore the immune-modulatory characteristics of the live bacterium at the intestinal level and its impact on the morpho-functional aspects of the intestinal mucosa. assays revealed the ability of subsp. to survive the gastric and intestinal simulated conditions and to satisfactorily adhere to the human intestinal epithelial cells. The bacterium was shown to be sensitive to an array of antibiotics. Immuno-modulation studies with mice orally administered with subsp. showed a higher number of IgA positive cells in the small intestine, a higher concentration of the anti-inflammatory cytokine IL-10 in the intestinal mucosa, as well as an increase in the number of goblet cells. The anti-inflammatory cytokine miR146a was found to be increased in the ileum and brain. Furthermore, it increases the number of goblet cells which contribute to intestinal barrier integrity. Taken together, our findings reflect the ability of the tested bacterium to modulates the intestinal homeostasis and immune response. Detailed safety unpublished studies and genome data support our finding. The strain subsp. has been filed in a provisional patent; a U.S. Provisional Application No. 62/916,921 entitled "Probiotics Composition and Methods." Future studies are still needed to validate the potential utilization of this strain as functional food and its potential probiotic effect.

摘要

对从野生蓝莓果实微生物群中分离出的一种新型细菌(亚种)的免疫调节能力和肠道形态功能方面进行了研究。该细菌的全基因组鸟枪法测序确定了其新的分类地位,并表明其不存在致病基因。尽管该细菌被用于蓝莓发酵并增强其对神经退行性疾病、糖尿病和癌症的抗炎作用,但尚无研究评估该细菌对健康的影响。在本研究中,我们使用了多种检测方法来评估该亚种与肠黏膜的相互作用及其对局部免疫反应的影响。研究了该菌株的抗生素敏感性、对胃和肠道环境的耐受性以及附着于人类肠上皮细胞(Caco-2和HT-29)的能力。此外,使用Balb/c小鼠来探究该活细菌在肠道水平的免疫调节特性及其对肠黏膜形态功能方面的影响。检测显示该亚种能够在模拟的胃和肠道条件下存活,并能令人满意地附着于人类肠上皮细胞。该细菌对一系列抗生素敏感。对口服该亚种的小鼠进行的免疫调节研究表明,小肠中IgA阳性细胞数量增加,肠黏膜中抗炎细胞因子IL-10浓度升高,杯状细胞数量增加。发现抗炎细胞因子miR146a在回肠和大脑中增加。此外,它增加了有助于维持肠道屏障完整性的杯状细胞数量。综上所述,我们的研究结果反映了受试细菌调节肠道稳态和免疫反应的能力。未发表的详细安全性研究和基因组数据支持了我们的发现。该亚种菌株已提交临时专利;美国临时专利申请号62/916,921,题为“益生菌组合物和方法”。仍需要进一步的研究来验证该菌株作为功能性食品的潜在用途及其潜在的益生菌效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f1/8258396/dcd0aa79f0ed/fmicb-12-569119-g009.jpg
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