Fecal Microbiota Transplantation Increases Colonic IL-25 and Dampens Tissue Inflammation in Patients with Recurrent Clostridioides difficile.
Fecal Microbiota Transplantation Increases Colonic IL-25 and Dampens Tissue Inflammation in Patients with Recurrent Clostridioides difficile.
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DOI：
10.1128/msphere.00669-21
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发表时间：
2021-10-27
期刊：
影响因子：
4.8
通讯作者：
Marie C
中科院分区：
文献类型：
--
作者：
Jan N;Hays RA;Oakland DN;Kumar P;Ramakrishnan G;Behm BW;Petri WA Jr;Marie C
艰难梭菌感染(CDI)是美国最常见的医院获得性感染。抗生素引起的微生物失调是肿瘤易感性的主要原因，粪便微生物区系移植(FMT)已成为治疗复发的有效方法。我们以前在CDI的小鼠模型中证明，抗生素诱导的生物失调减少了结肠白细胞介素25(IL-25)的表达，而FMT通过恢复IL-25信号来部分保护。在这里，我们在人类中进行了一项前瞻性研究，以测试FMT是否诱导复发CDI(RCDI)患者结肠中IL-25的表达。分别于FMT时和60 后采集结肠活检标本和血样。分析FMT前后结肠活检标本的IL-25蛋白水平、总组织转录组和上皮相关微生物区系，并对外周免疫细胞进行免疫表型分析。FMT增加了结肠微生物区系的α多样性和结肠组织中IL-25的水平。此外，FMT增加了体内平衡基因的表达，抑制了炎症基因的表达。最后，FMT后外周血中Th17细胞减少。细胞因子IL-25水平的升高伴随炎症反应的减少与FMT的部分作用是一致的，其作用是通过恢复2型免疫的共生激活来保护CDI的复发。重要：粪便微生物移植(FMT)对大多数患者来说是艰难梭菌感染的有效治疗方法；然而，引入复杂的微生物混合物也对一些患者产生了意想不到的后果。到目前为止，试图创造一种概括FMT疗效的标准化益生菌疗法的尝试尚未成功。我们试图了解在接受FMT治疗艰难梭菌复发感染的患者中，哪些免疫标志物发生了变化，并确定了一种免疫信号分子IL-25，该分子可通过FMT恢复。这一发现表明，用IL-25辅助治疗艰难梭菌感染可能是有用的。
Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility, and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of interleukin 25 (IL-25) and that FMT protected in part by restoring IL-25 signaling. Here, we conducted a prospective study in humans to test if FMT induced IL-25 expression in the colons of patients with recurrent CDI (rCDI). Colonic biopsy specimens and blood were collected at the time of FMT and 60 days later. Colon biopsy specimens were analyzed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after FMT, and peripheral immune cells were immunophenotyped. FMT increased alpha diversity of the colonic microbiota and levels of IL-25 in colonic tissue. In addition, FMT increased expression of homeostatic genes and repressed inflammatory genes. Finally, circulating Th17 cells were decreased post-FMT. The increase in levels of the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for C. difficile infection for most patients; however, introducing a complex mixture of microbes also has had unintended consequences for some patients. Attempts to create a standardized probiotic therapeutic that recapitulates the efficacy of FMT have been unsuccessful to date. We sought to understand what immune markers are changed in patients undergoing FMT to treat recurrent C. difficile infection and identified an immune signaling molecule, IL-25, that was restored by FMT. This finding indicates that adjunctive therapy with IL-25 could be useful in treating C. difficile infection.