Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility

Sequencing of the bacterial 16S rRNA gene revealed that these treatments significantly altered the ileal and cecal microbiota, resulting in increases in the Firmicutes:Bacteriodetes ratio, and abundances of lactobacilli and butyrate producing genera. Both treatments partially normalized the peripheral inflammatory state, reducing plasma cytokine, chemokine and TLR-4 activity levels. The proinflammatory islet transcriptome was more extensively normalized by HCD and immune-fluorescent staining revealed reductions in β-cell chemokine expression. HCD and antibiotic treatment did not normalize BB rat PBMC hyper-responsiveness to ex vivo mitogen stimulation. Combined, these studies link islet-level T1D susceptibility in BB rats to a genetically controlled innate inflammatory state that is influenced by environmental determinants encompassing the diet and the intestinal microbiota.对细菌16S核糖体RNA基因（16S rRNA gene）进行测序的结果显示，上述干预措施显著改变了回肠与盲肠的微生物群组成，使得厚壁菌门（Firmicutes）与拟杆菌门（Bacteroidetes，原文此处拼写为Bacteriodetes）的丰度比值升高，同时提升了乳杆菌属（lactobacilli）及产丁酸菌属（butyrate producing genera）的相对丰度。两种干预措施均能部分改善外周炎症状态，降低血浆细胞因子、趋化因子与Toll样受体4（TLR-4）的活性水平。促炎性胰岛转录组经高胆固醇饮食（HCD，High Cholesterol Diet）干预后得到了更为全面的正常化恢复，免疫荧光染色结果显示β细胞（β-cell）的趋化因子表达量有所降低。高胆固醇饮食与抗生素治疗均未能使BB大鼠（BB rat）的外周血单个核细胞（PBMC，peripheral blood mononuclear cell）在体外有丝分裂原刺激（ex vivo mitogen stimulation）下的过度反应性恢复至正常水平。综合上述研究结果，本研究将BB大鼠胰岛层面的1型糖尿病（T1D，Type 1 Diabetes）易感性与受遗传调控的先天炎症状态建立了关联，该炎症状态受到涵盖饮食与肠道微生物群的环境因素的影响。