Gut-derived immunoglobulin A (IgA) is the most abundant antibody secreted in the gut that shapes gut microbiota composition and functionality. However, most of the microbial antigens targeted by gut IgA remain unknown, and the functional effects of IgA targeting these antigens are currently understudied. This study provides a framework for identifying and characterizing gut microbiota antigens targeted by gut IgA. We developed a small intestinal ex vivo culture assay to harvest lamina propria IgA from gnotobiotic mice, with the aim of identifying antigenic targets in a model human gut commensal, Bacteroides thetaiotaomicron VPI-5482. Colonization by B. thetaiotaomicron induced a microbe-specific IgA response that was reactive against diverse antigens, including capsular polysaccharides, lipopolysaccharides, and proteins. IgA against microbial protein antigens targeted membrane and secreted proteins with diverse functionalities, including an IgA specific against proteins of the polysaccharide utilization locus (PUL) that are necessary for utilization of fructan, which is an important dietary polysaccharide. Further analyses demonstrated that the presence of dietary fructan increased the production of fructan PUL-specific IgA, which then downregulated the expression of fructan PUL in B. thetaiotaomicron, both in vivo and in vitro Since the expression of fructan PUL has been associated with the ability of B. thetaiotaomicron to colonize the gut in the presence of dietary fructans, our work suggests a novel role for gut IgA in regulating microbial colonization by modulating their metabolism.IMPORTANCE Given the significant impact that gut microbes have on our health, it is essential to identify key host and environmental factors that shape this diverse community. While many studies have highlighted the impact of diet on gut microbiota, little is known about how the host regulates this critical diet-microbiota interaction. In our present study, we discovered that gut IgA targeted a protein complex involved in the utilization of an important dietary polysaccharide: fructan. While the presence of dietary fructans was previously thought to allow unrestricted growth of fructan-utilizing bacteria, our work shows that gut IgA, by targeting proteins responsible for fructan utilization, provides the host with tools that can restrict the microbial utilization of such polysaccharides, thereby controlling their growth.

中文翻译：

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肠道 IgA 调节肠道共生多形拟杆菌定植中果聚糖多糖利用位点的表达。


肠源性免疫球蛋白 A (IgA) 是肠道中分泌最丰富的抗体，可塑造肠道微生物群的组成和功能。然而，肠道 IgA 靶向的大多数微生物抗原仍然未知，并且针对这些抗原的 IgA 的功能效应目前尚未得到充分研究。这项研究为识别和表征肠道 IgA 靶向的肠道微生物群抗原提供了一个框架。我们开发了一种小肠离体培养测定法，从限生小鼠中收获固有层 IgA，目的是鉴定人类肠道共生模型 Bacteroides thetaiotaomicron VPI-5482 中的抗原靶点。 B. thetaiotaomicron 的定植诱导了微生物特异性 IgA 反应，该反应对多种抗原有反应，包括荚膜多糖、脂多糖和蛋白质。针对微生物蛋白抗原的 IgA 靶向具有多种功能的膜和分泌蛋白，包括针对多糖利用位点 (PUL) 蛋白质的特异性 IgA，该蛋白是利用果聚糖（一种重要的膳食多糖）所必需的。进一步的分析表明，膳食果聚糖的存在增加了果聚糖 PUL 特异性 IgA 的产生，然后在体内和体外下调 B. thetaiotaomicron 中果聚糖 PUL 的表达，因为果聚糖 PUL 的表达与能力相关B. thetaiotaomicron 在膳食果聚糖存在的情况下在肠道中定殖，我们的工作表明肠道 IgA 在通过调节微生物的新陈代谢来调节微生物定植方面发挥着新的作用。 重要性 鉴于肠道微生物对我们的健康具有重大影响，因此至关重要确定塑造这个多样化社区的关键宿主和环境因素。 虽然许多研究强调了饮食对肠道微生物群的影响，但人们对宿主如何调节这种关键的饮食与微生物群相互作用知之甚少。在我们目前的研究中，我们发现肠道 IgA 靶向一种参与重要膳食多糖：果聚糖利用的蛋白质复合物。虽然膳食果聚糖的存在以前被认为可以使利用果聚糖的细菌不受限制地生长，但我们的工作表明，肠道 IgA 通过靶向负责果聚糖利用的蛋白质，为宿主提供了可以限制微生物利用此类多糖的工具，从而控制它们的生长。