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益生菌调节宿主免疫反应并与肠道微生物群相互作用:塑造其组成并介导抗生素耐药性。

Probiotics Modulate Host Immune Response and Interact with the Gut Microbiota: Shaping Their Composition and Mediating Antibiotic Resistance.

机构信息

College of Pharmacy, Al Ain University, Abu Dhabi P.O. Box 64141, United Arab Emirates.

AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi P.O. Box 112612, United Arab Emirates.

出版信息

Int J Mol Sci. 2023 Sep 7;24(18):13783. doi: 10.3390/ijms241813783.

DOI:10.3390/ijms241813783
PMID:37762089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10531388/
Abstract

The consortium of microbes inhabiting the human body, together with their encoded genes and secreted metabolites, is referred to as the "human microbiome." Several studies have established a link between the composition of the microbiome and its impact on human health. This impact spans local gastrointestinal inflammation to systemic autoimmune disorders and neurodegenerative diseases such as Alzheimer's and Autism. Some of these links have been validated by rigorous experiments that identify specific strains as mediators or drivers of a particular condition. Consequently, the development of probiotics to compensate for a missing beneficial microbe(s) has advanced and become popular, especially in the treatment of irritable bowel diseases and to restore disrupted gut flora after antibiotic administration. The widespread use of probiotics is often advocated as a natural ecological therapy. However, this perception is not always accurate, as there is a potential for unexpected interactions when administering live microbial cultures. Here, we designed this research to explore the intricate interactions among probiotics, the host, and microbes through a series of experiments. Our objectives included assessing their immunomodulatory effects, response to oral medications, impact on microbial population dynamics, and mediation of antibiotic resistance. To achieve these goals, we employed diverse experimental protocols, including cell-based enzyme -linked immunosorbent assay (ELISA), antibiotic susceptibility testing, antimicrobial activity assays, computational prediction of probiotic genes responsible for antibiotic resistance, polymerase chain reaction (PCR)-based validation of predicted genes, and survival assays of probiotics in the presence of selected oral medications. Our findings highlight that more than half of the tested probiotics trigger an inflammatory response in the Caco-2 cell line, are influenced by oral medications, exhibit antibacterial activity, and possess genes encoding antimicrobial resistance. These results underscore the necessity for a reevaluation of probiotic usage and emphasize the importance of establishing regulations to govern probiotic testing, approval, and administration.

摘要

人体中栖息的微生物群落及其编码基因和分泌代谢物被称为“人类微生物组”。多项研究已经证实了微生物组的组成与其对人类健康的影响之间存在关联。这种影响范围从局部胃肠道炎症到全身性自身免疫性疾病和神经退行性疾病,如阿尔茨海默病和自闭症。其中一些关联已经通过严格的实验得到了验证,这些实验确定了特定的菌株是特定疾病的介质或驱动因素。因此,开发益生菌来弥补缺失的有益微生物已经取得了进展,并变得流行起来,特别是在治疗肠易激综合征和恢复抗生素治疗后破坏的肠道菌群方面。益生菌的广泛使用通常被倡导为一种自然生态疗法。然而,这种看法并不总是准确的,因为在给予活体微生物培养物时存在潜在的意外相互作用。在这里,我们设计了这项研究,通过一系列实验来探索益生菌、宿主和微生物之间的复杂相互作用。我们的目标包括评估它们的免疫调节作用、对口服药物的反应、对微生物种群动态的影响以及对抗生素耐药性的介导。为了实现这些目标,我们采用了多种实验方案,包括基于细胞的酶联免疫吸附测定(ELISA)、抗生素敏感性测试、抗菌活性测定、预测益生菌基因对抗生素耐药性的计算、基于聚合酶链反应(PCR)的预测基因验证以及在选定口服药物存在下益生菌的存活测定。我们的研究结果表明,超过一半的测试益生菌会在 Caco-2 细胞系中引发炎症反应,受口服药物影响,具有抗菌活性,并具有编码抗菌耐药性的基因。这些结果强调了重新评估益生菌使用的必要性,并强调了制定法规来管理益生菌测试、批准和管理的重要性。

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