Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, IL.
Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, IL..
J Nutr Biochem. 2018 Apr;54:95-104. doi: 10.1016/j.jnutbio.2017.12.002. Epub 2017 Dec 10.
Inflammatory bowel diseases (IBD) are caused by the convergence of microbial, environmental, and genetic factors. Diet significantly alters these interactions by affecting both the host and microbiome. Using a mucosal inflammatory model that resembles the human condition of ileal pouchitis, we investigated the effects of Control (CONT) or Antioxidant (AOX) diet, containing pharmacologically relevant levels of 4 micronutrients, on disease risk in wild-type and IL-10 animals following surgical self-filling (SF) ileal blind loop placement. Although no differences were found in body weight change or survival, IL-10 CONT animals had significantly larger lymphoid organs compared with IL-10 AOX or with WT. SF loops from IL-10 CONT loop mucosa demonstrated histological inflammation, characterized by goblet cell depletion, increased mucosal myeloperoxidase (MPO), and elevated IFNγ, TNFα, and IL-17α gene expression, which AOX attenuated. AOX elevated luminal IgA in IL-10 animals, but not significantly in WT. In IL-10 animals, AOX significantly decreased the percentage of CD4 + T-bet and CD4 + RORγ T-cells compared with CONT, with no changes in CD4 + Foxp3+ Treg cells. 16S rRNA gene sequencing demonstrated AOX increased microbial alpha diversity compared with CONT in both genotypes. Notably, colonizing germ-free IL-10 hosts with CONT bacterial communities, but not AOX, recapitulated the inflammatory phenotype. Collectively, these findings highlight that common dietary antioxidant micronutrients reshape the gut microbial community to mitigate intestinal inflammatory profiles in genetically susceptible hosts. Insights into the dietary-immune-microbial nexus may improve understanding for recurrent inflammatory episodes in susceptible patient populations and opportunities for practical therapeutics to restore immune and microbial homeostasis.
炎症性肠病（IBD）是由微生物、环境和遗传因素的融合引起的。饮食通过影响宿主和微生物组显著改变这些相互作用。我们使用一种类似于人类回肠袋炎的粘膜炎症模型，研究了在手术自填充（SF）回肠盲袢放置后，含有药理相关水平的 4 种微量营养素的对照（CONT）或抗氧化（AOX）饮食对野生型和 IL-10 动物疾病风险的影响。尽管在体重变化或存活率方面没有差异，但与 IL-10 AOX 或 WT 相比，IL-10 CONT 动物的淋巴器官明显更大。来自 IL-10 CONT 环粘膜的 SF 环显示出组织学炎症，其特征是杯状细胞耗竭、粘膜髓过氧化物酶（MPO）增加和 IFNγ、TNFα 和 IL-17α 基因表达升高，AOX 减轻了这些变化。AOX 增加了 IL-10 动物的腔 IgA，但在 WT 中没有显著增加。在 IL-10 动物中，与 CONT 相比，AOX 显著降低了 CD4 + T-bet 和 CD4 + RORγ T 细胞的百分比，而 CD4 + Foxp3+ Treg 细胞没有变化。16S rRNA 基因测序表明，与 CONT 相比，AOX 增加了两种基因型的微生物 α多样性。值得注意的是，用 CONT 细菌群落定植无菌 IL-10 宿主而不是 AOX 重现了炎症表型。总之，这些发现强调了常见的饮食抗氧化微量营养素重塑肠道微生物群落，以减轻遗传易感宿主的肠道炎症特征。对饮食-免疫-微生物关系的深入了解可能有助于理解易感患者群体中反复发生的炎症发作，并为恢复免疫和微生物平衡提供实际治疗机会。
