Nat. Med：抗生素使用或可加重过敏和哮喘发作

3月25日，发表在《自然—医学》（Nature Medicine）上的一项报告称，长期服用抗生素或生活在无菌环境下的小鼠容易患上严重的过敏和哮喘。这项发现支持了“卫生假说”理论，该理论认为一定量的细菌能预防过敏疾病的发生。

据多项流行病研究显示，肠道细菌的改变与呼吸道过敏疾病比如哮喘，存在一定关联。但导致该关联产生的细胞和分子的具体种类目前仍是未知数。

David Artis和同事发现服用五种抗生素或者在无菌条件下培养的小鼠产生的呼吸道过敏疾病更严重，而这种疾病原本是由房屋灰尘颗粒中的过敏原导致的。在这项研究中，服用抗生素会导致小鼠血液中与过敏有关的IgE抗生素、嗜碱性粒细胞以及免疫细胞的浓度升高。正常情况下，肠道中的有益菌会刺激免疫B细胞以限制B细胞分泌IgE，而在抗生素的作用下，肠道有益菌发生变化，进而放任B细胞分泌更多IgE，IgE又作用于骨髓嗜碱性粒细胞前体并促进其发育。

这项研究在肠道菌群如何影响骨髓中嗜碱性粒细胞的发育和如何导致过敏疾病之间建立起了一种新的关联。

doi:10.1038/nm.2657
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Commensal bacteria–derived signals regulate basophil hematopoiesis and allergic inflammation

David A Hill, Mark C Siracusa, Michael C Abt, Brian S Kim, Dmytro Kobuley, Masato Kubo, Taku Kambayashi, David F LaRosa, Ellen D Renner, Jordan S Orange, Frederic D Bushman & David Artis

Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (TH2) cytokine-dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we find that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum IgE concentrations, increased steady-state circulating basophil populations and exaggerated basophil-mediated TH2 cell responses and allergic inflammation. Elevated serum IgE levels correlated with increased circulating basophil populations in mice and subjects with hyperimmunoglobulinemia E syndrome. Furthermore, B cell–intrinsic expression of myeloid differentiation factor 88 (MyD88) was required to limit serum IgE concentrations and circulating basophil populations in mice. Commensal-derived signals were found to influence basophil development by limiting proliferation of bone marrow–resident precursor populations. Collectively, these results identify a previously unrecognized pathway through which commensal-derived signals influence basophil hematopoiesis and susceptibility to TH2 cytokine–dependent inflammation and allergic disease.