Department of Biology, University of British Columbia Okanagan, ASC 368, 3333 Univ. Way, The Irving K. Barber School of Arts and Sciences, Kelowna, BC, Canada V1V 1V7.
Am J Physiol Gastrointest Liver Physiol. 2012 Oct;303(7):G825-36. doi: 10.1152/ajpgi.00327.2011. Epub 2012 Jul 19.
Inflammatory bowel disease, inclusive of Crohn's disease and ulcerative colitis, consists of immunologically mediated disorders involving the microbiota in the gastrointestinal tract. Lavender oil is a traditional medicine used to relieve many gastrointestinal disorders. The goal of this study was to examine the therapeutic effects of the essential oil obtained from a novel lavender cultivar, Lavandula×intermedia cultivar Okanagan lavender (OLEO), in a mouse model of acute colitis caused by Citrobacter rodentium. In colitic mice, oral gavage with OLEO resulted in less severe disease, including decreased morbidity and mortality, reduced intestinal tissue damage, and decreased infiltration of neutrophils and macrophages, with reduced levels of TNF-α, IFN-γ, IL-22, macrophage inflammatory protein-2α, and inducible nitric oxide synthase expression. This was associated with increased levels of regulatory T cell populations compared with untreated colitic mice. Recently, we demonstrated that the composition of the enteric microbiota affects susceptibility to C. rodentium-induced colitis. Here, we found that oral administration of OLEO induced microbiota enriched with members of the phylum Firmicutes, including segmented filamentous bacteria, which are known to protect against the damaging effects of C. rodentium. Additionally, during infection, OLEO treatment promoted the maintenance of microbiota loads, with specific increases in Firmicutes bacteria and decreases in γ-Proteobacteria. We observed that Firmicutes bacteria were intimately associated with the apical region of the intestinal epithelial cells during infection, suggesting that their protective effect was through contact with the gut wall. Finally, we show that OLEO inhibited C. rodentium growth and adherence to Caco-2 cells, primarily through the activities of 1,8-cineole and borneol. These results indicate that while OLEO promoted Firmicutes populations, it also controlled pathogen load through antimicrobial activity. Overall, our results reveal that OLEO can protect against colitis through the microbial-immunity nexus and that a pharmacological agent, in this case OLEO, alters the normal enteric microbiota.
炎症性肠病(包括克罗恩病和溃疡性结肠炎)是一种免疫介导的疾病,涉及胃肠道中的微生物群。薰衣草油是一种传统药物,用于缓解许多胃肠道疾病。本研究的目的是研究新型薰衣草品种 Lavandula×intermedia 栽培品种奥卡纳根薰衣草(OLEO)精油在柠檬酸杆菌引起的急性结肠炎小鼠模型中的治疗作用。在结肠炎小鼠中,口服 OLEO 可导致疾病减轻,包括发病率和死亡率降低、肠道组织损伤减少、中性粒细胞和巨噬细胞浸润减少,TNF-α、IFN-γ、IL-22、巨噬细胞炎症蛋白-2α 和诱导型一氧化氮合酶表达减少。与未经治疗的结肠炎小鼠相比,这与调节性 T 细胞群体水平升高有关。最近,我们证明肠道微生物群的组成会影响柠檬酸杆菌诱导的结肠炎易感性。在这里,我们发现口服 OLEO 可诱导厚壁菌门成员丰富的肠道微生物群,包括已知可防止柠檬酸杆菌破坏性影响的分段丝状菌。此外,在感染期间,OLEO 治疗促进了微生物群负荷的维持,厚壁菌门细菌的特定增加和γ-变形菌的减少。我们观察到,在感染过程中,厚壁菌门细菌与肠上皮细胞的顶端区域密切相关,这表明其保护作用是通过与肠道壁接触实现的。最后,我们表明 OLEO 通过 1,8-桉油醇和龙脑的活性抑制柠檬酸杆菌的生长和对 Caco-2 细胞的粘附。这些结果表明,虽然 OLEO 促进了厚壁菌门种群的生长,但它也通过抗菌活性控制了病原体负荷。总的来说,我们的结果表明,OLEO 可以通过微生物-免疫网络来保护免受结肠炎的侵害,并且药理学制剂(在这种情况下为 OLEO)会改变正常的肠道微生物群。