Abstract:
Short-chain fatty acids (SCFAs) have been proposed to have anti-inflammatory effects and improve immune homeostasis. We aimed to examine the effects of SCFAs on skin phenotype, systemic inflammation, and gut microbiota in mice with psoriasis-like inflammation. Imiquimod (IMQ)-treated C57BL/6 mice served as the study model. We conducted a metagenomic association study of IMQ-mice treated with SCFAs or anti-IL-17 antibody using whole-genome shotgun sequencing. The associations among SCFA supplements, skin thickness, circulating inflammatory profiles, and fecal microbiota profiles were investigated. The microbiome study was performed using pipelines for phylogenetic analysis, functional gene analysis, and pathway analysis. In IMQ-treated mice, there were increases in skin thickness and splenic weight, as well as unique fecal microbial profiles. SCFAs ameliorated IMQ-induced skin thickening, splenic weight gain, and serum IL-17F levels, with results that were comparable with those receiving anti-IL-17 treatment. IMQ-treated mice receiving SCFAs had greater microbial diversity than mice treated with IMQ alone. SCFAs and anti-IL17 treatment were associated with alteration of gut microbiota, with increased prevalences of Oscillospiraceae and Lachnopiraceae and decreased prevalences of Muribaculaceae and Bacteroides, which have been predicted to be associated with increased glycan degradation, phenylalanine metabolism, and xylene degradation. SCFAs may mitigate IMQ-induced skin thickening and IL-17F levels and alter fecal microbiota profiles in IMQ-treated mice.
摘要:
短链脂肪酸(SCFA)已被提出具有抗炎作用并改善免疫稳态。我们旨在研究SCFA对皮肤表型的影响,全身性炎症,和牛皮癣样炎症小鼠的肠道微生物群。咪喹莫特(IMQ)处理的C57BL/6小鼠用作研究模型。我们使用全基因组鸟枪测序对用SCFA或抗IL-17抗体治疗的IMQ小鼠进行了宏基因组关联研究。SCFA补充剂之间的关联,蒙皮厚度,循环炎症谱,和粪便微生物区系进行了调查。微生物组研究使用管道进行系统发育分析,功能基因分析,和路径分析。在IMQ处理的小鼠中,皮肤厚度和脾脏重量增加,以及独特的粪便微生物概况。SCFA改善了IMQ诱导的皮肤增厚,脾体重增加,和血清IL-17F水平,结果与接受抗IL-17治疗的患者相当。接受SCFA的IMQ处理的小鼠比单独用IMQ处理的小鼠具有更大的微生物多样性。SCFA和抗IL17治疗与肠道微生物群的改变有关,随着螺旋藻科和落叶草科的流行率增加,而半枝杆菌科和拟杆菌属的流行率降低,预测与聚糖降解增加有关,苯丙氨酸代谢,和二甲苯降解。SCFA可以减轻IMQ诱导的皮肤增厚和IL-17F水平,并改变IMQ治疗小鼠的粪便微生物群。