Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Mucosal Immunol. 2018 May;11(3):785-795. doi: 10.1038/mi.2017.75. Epub 2017 Oct 25.
The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4 T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL19 in vitro, and exhibit a dampened ability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC-dependent mechanisms that are inhibited by SCFAs.
哺乳动物的胃肠道中栖息着一个具有代谢活性的微生物群落，这些代谢活动对宿主的健康至关重要，其中包括能够调节免疫细胞效应功能的代谢产物。万古霉素处理的小鼠的微生物组和代谢物谱发生改变，表现出 Th2 细胞反应的加剧，并且更容易发生过敏性肺炎症。在这里，我们表明，通过调节 T 细胞和树突状细胞（DC）的活性，短链脂肪酸（SCFAs）的饮食补充可以改善这种增强的哮喘易感性。用 SCFAs 处理的失调小鼠产生较少的白细胞介素 4（IL4）产生的 CD4 T 细胞，并且循环免疫球蛋白 E（IgE）水平降低。此外，暴露于 SCFAs 的 DC 激活 T 细胞的能力较弱，在体外对 CCL19 的反应性迁移性降低，并且向肺部引流节点输送吸入过敏原的能力减弱。因此，我们的数据表明，肠道菌群失调可以通过 T 细胞和 DC 依赖的机制来加剧过敏性肺炎症，而 SCFAs 可以抑制这些机制。
