Commensal fungal communities in the regulation of immunity and intestinal inflammation

摘要 几十年的研究表明，肠道细菌对调节体内平衡和保护至关重要。 免疫反应。然而，最近的研究表明，真菌和病毒等其他参与者具有很高的 有可能影响这些进程。虽然肠道真菌之间重要的跨界关系 （真菌生物群）和细菌最近已经公布，真菌如何影响肠道内稳态， 炎症和对炎症性肠病（IBD）的治疗干预的反应仍然不太清楚。 在先前的工作中，我们定义了肠道菌群通过相互作用对局部和肠道远端免疫的深刻影响， 与CX3CR1+单核吞噬细胞或通过塑造宿主抗体库，影响真菌 奴隶制。我们定义这些过程在IBD中受到影响。在一项多中心安慰剂对照临床试验中， 在溃疡性结肠炎（UC）中进行粪便微生物群移植（FMT）的试验，我们最近确定真菌 清除和针对白色念珠菌的免疫激活减弱与对治疗的应答相关。这些 研究结果表明，肠道菌群在治疗干预的疗效和反应中可能发挥作用。在 初步研究表明，存在丰富的遗传和表型多样性的机会， IBD患者结肠粘膜中占主导地位的念珠菌菌株。我们发现，这些分离株的不同之处在于， 导致宿主细胞损伤的能力，并且在个体之间具有功能多样性。在这次竞争性的更新中， 提出旨在破译由患者相关菌株引起的炎症过程的研究。我们 假设这些微生物通过产生 在特定菌株水平上调节的因素。这项研究的结果将绘制人类肠道菌群 这可能为炎症性疾病的靶向新疗法和联合疗法提供基础。

Abstract Decades of research have revealed that intestinal bacteria are critical for regulating homeostatic and protective immune responses. However, recent studies suggest that additional players such as fungi and viruses have high potential to influence these processes. While important trans-kingdom relationships between gut fungi (mycobiota) and bacteria have been recently unveiled, how fungi influence intestinal homeostasis, states of inflammation and responses to therapeutic interventions for Inflammatory Bowel Disease (IBD) is still less clear. In prior works, we defined profound effects of gut mycobiota on local and gut distal immunity through interaction with CX3CR1+ mononuclear phagocyte or by shaping host antibody repertoires that influence fungal commensalism. We defined that these processes are affected in IBD. In a multicenter placebo-controlled clinical trial of fecal microbiota transplantation (FMT) in Ulcerative colitis (UC) we recently determined that fungal clearance and blunted immune activation against Candida albicans correlates with a response to therapy. These findings suggest a possible role of gut mycobiota in efficacy of and response to therapeutic interventions. In preliminary studies we demonstrate the presence of rich genetic and phenotypic diversity of opportunistic Candida strains that dominated the colonic mucosa of IBD patients. We found that these isolates differ by their ability to cause host cell damage and are functionally diverse across individuals. In this competitive renewal we propose studies aiming to decipher the processes on inflammation caused by patient-associated strains. We hypothesize that these organisms influence inflammation and response to therapy through the production of factors that are regulated at strain-specific level. The results of this study will map the human gut mycobiota functionally and might provide a basis for targeted novel therapies and co-therapies for inflammatory diseases.