PDF(Pubmed)
Abstract：
Commensal enteric bacteria have evolved systems that enable growth in the ecologic niche of the host gastrointestinal tract. Animals evolved parallel mechanisms to survive the constant exposure to bacteria and their metabolic by-products. We propose that drug transporters encompass a crucial system to managing the gut microbiome. Drug transporters are present in the apical surface of gut epithelia. They detoxify cells from small molecules and toxins (xenobiotics) in the lumen. Here, we review what is known about commensal structure in the absence of the transporter ABCB1/P-glycoprotein in mammalian models. Knockout or low-activity alleles of ABCB1 lead to dysbiosis, Crohn\'s disease and ulcerative colitis in mammals. However, the exact function of ABCB1 in these contexts remain unclear. We highlight emerging models-the zebrafish Danio rerio and sea urchin Lytechinus pictus-that are poised to help dissect the fundamental mechanisms of ATP-binding cassette (ABC) transporters in the tolerance of commensal and pathogenic communities in the gut. We and others hypothesize that ABCB1 plays a direct role in exporting inflammatory bacterial products from host epithelia. Interdisciplinary work in this research area will lend novel insight to the transporter-mediated pathways that impact microbiome community structure and accelerate the pathogenesis of inflammatory bowel disease when perturbed. This article is part of the theme issue \'Sculpting the microbiome: how host factors determine and respond to microbial colonization\'.
摘要：
共生肠细菌已经进化出能够在宿主胃肠道的生态壁龛中生长的系统。动物进化出平行的机制来在持续暴露于细菌及其代谢副产物中存活。我们建议药物转运蛋白包含一个管理肠道微生物组的关键系统。药物转运蛋白存在于肠上皮细胞的顶端表面。它们使细胞从内腔中的小分子和毒素（异种生物）中解毒。这里,我们回顾了哺乳动物模型中缺乏转运体ABCB1/P-糖蛋白的共生结构。基因敲除或ABCB1的低活性等位基因导致生态失调，哺乳动物克罗恩病和溃疡性结肠炎。然而,ABCB1在这些情况下的确切功能尚不清楚.我们重点介绍了新兴的模型-斑马鱼Daniorerio和海胆Lytechinuspictus-有望帮助剖析ATP结合盒（ABC）转运蛋白在肠道共生和致病群落耐受性中的基本机制。我们和其他人假设ABCB1在从宿主上皮输出炎性细菌产物中起直接作用。该研究领域的跨学科工作将为影响微生物群落结构的转运蛋白介导的途径提供新的见解，并在受到干扰时加速炎症性肠病的发病机理。本文是“塑造微生物组：宿主因素如何决定和响应微生物定植”主题的一部分。
