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母乳中的分泌型免疫球蛋白 A 通过调节肠道菌群预防哮喘。

Secretory IgA in breast milk protects against asthma through modulation of the gut microbiota.

机构信息

Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.

出版信息

Cell Rep. 2024 Oct 22;43(10):114835. doi: 10.1016/j.celrep.2024.114835. Epub 2024 Oct 4.

Abstract

Asthma susceptibility is linked to dysbiosis in early-life gut microbiota, and the antibody secretory immunoglobulin (Ig)A (SIgA) is a key determinant of gut microbiota composition. SIgA is obtained through breast milk during the critical early-life window. We use a mouse model of SIgA deficiency and the house dust mite (HDM) model of asthma to elucidate the role of maternal SIgA in modulating the early-life gut microbiota and asthma protection. Mice that do not receive maternal SIgA display a transient bloom of segmented filamentous bacteria (SFB) in the small intestine during the early post-weaning period. Mice that do not receive maternal SIgA also display elevated T helper type 17 (Th17) cell activation in the intestine, which persists into adulthood and is associated with more severe inflammation in response to the HDM model of asthma. This study demonstrates a mechanism by which breast-milk-derived SIgA influences immune development and asthma susceptibility by modulating the early-life gut microbiota.

摘要

哮喘易感性与生命早期肠道微生物群的失调有关,而分泌型免疫球蛋白 A(SIgA)是肠道微生物群组成的关键决定因素。SIgA 是在生命早期的关键窗口期通过母乳获得的。我们使用 SIgA 缺乏的小鼠模型和屋尘螨(HDM)哮喘模型来阐明母体 SIgA 在调节生命早期肠道微生物群和哮喘保护中的作用。未接受母体 SIgA 的小鼠在断奶后早期的小肠中会短暂出现大量的丝状菌(SFB)。未接受母体 SIgA 的小鼠还表现出肠道中 Th17 细胞激活增加,这种现象持续到成年期,并与对 HDM 哮喘模型的炎症反应更严重有关。这项研究表明,母乳衍生的 SIgA 通过调节生命早期肠道微生物群来影响免疫发育和哮喘易感性的机制。

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