Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Front Immunol. 2018 Nov 9;9:2557. doi: 10.3389/fimmu.2018.02557. eCollection 2018.
Diet composition may play a crucial role in shaping host immune responses and commensal gut microbiota populations. Bioactive dietary components, such as inulin, have been extensively studied for their bioactive properties, particularly in modulating gut immune function and reducing inflammation. It has been shown that colonization with gastrointestinal parasitic worms (helminths) may alleviate chronic inflammation through promotion of T-helper cell type (Th) 2 and T-regulatory immune responses and alterations in the gut microbiome. In this study, we investigated if dietary inulin could modulate mucosal immune function in pigs during colonization with the porcine whipworm . infection induced a typical Th2-biased immune response characterized by transcriptional changes in Th2- and barrier function-related genes, accompanied by intestinal remodeling through increased epithelial goblet and tuft cell proliferation. We observed that inulin also up-regulated Th2-related immune genes (), and suppressed Th1-related pro-inflammatory genes () in the colon. Notably, inulin augmented the -induced responses with increased transcription of key Th2 and mucosal barrier genes (e.g., ), and synergistically suppressed pro-inflammatory genes, such as and . 16S rRNA sequencing of proximal colon digesta samples revealed that inulin supplementation reduced the abundance of bacterial phyla linked to inflammation, such as Proteobacteria and Firmicutes, and simultaneously increased Actinobacteria and Bacteroidetes. Interestingly, pigs treated with both inulin and displayed the highest Bacteroidetes: Firmicutes ratio and the lowest gut pH, suggesting an interaction of diet and helminth infection that stimulates the growth of beneficial bacterial species. Overall, our data demonstrate that infection and inulin co-operatively enhance anti-inflammatory immune responses, which is potentially mediated by changes in microbiota composition. Our results highlight the intricate interactions between diet, immune function and microbiota composition in a porcine helminth infection model. This porcine model should facilitate further investigations into the use of bioactive diets as immunomodulatory mediators against inflammatory conditions, and how diet and parasites may influence gut health.
饮食组成可能在塑造宿主免疫反应和共生肠道微生物群方面发挥关键作用。生物活性膳食成分,如菊粉,因其生物活性特性而被广泛研究,特别是在调节肠道免疫功能和减少炎症方面。已经表明,胃肠道寄生虫(蠕虫)的定植可以通过促进辅助性 T 细胞(Th)2 和调节性 T 免疫反应以及肠道微生物组的改变来减轻慢性炎症。在这项研究中,我们调查了膳食菊粉是否可以在猪感染猪鞭虫时调节粘膜免疫功能。感染诱导了典型的 Th2 偏向免疫反应,表现为与 Th2 和屏障功能相关基因的转录变化,伴随着通过增加上皮杯状细胞和微绒毛细胞增殖的肠道重塑。我们观察到菊粉也上调了 Th2 相关免疫基因(),并抑制了结肠中的 Th1 相关促炎基因()。值得注意的是,菊粉增强了 -诱导的反应,增加了关键 Th2 和粘膜屏障基因的转录(例如,),并协同抑制促炎基因,如和。近端结肠消化物样本的 16S rRNA 测序显示,菊粉补充剂减少了与炎症相关的细菌门的丰度,如变形菌门和厚壁菌门,同时增加了放线菌门和拟杆菌门。有趣的是,同时接受菊粉和处理的猪表现出最高的拟杆菌门:厚壁菌门比值和最低的肠道 pH 值,表明饮食和寄生虫感染的相互作用刺激了有益细菌的生长。总体而言,我们的数据表明,感染和菊粉协同增强抗炎免疫反应,这可能是通过微生物组组成的变化介导的。我们的结果强调了饮食、免疫功能和微生物组组成在猪寄生虫感染模型中的复杂相互作用。这种猪模型应该有助于进一步研究生物活性饮食作为针对炎症状态的免疫调节剂的用途,以及饮食和寄生虫如何影响肠道健康。