Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain.
Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.
Front Immunol. 2021 Jun 4;12:683387. doi: 10.3389/fimmu.2021.683387. eCollection 2021.
Fecal microbiota transplantation (FMT) is an effective procedure against infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient's mucosal immune response against the donor's microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the phylum and genus, with a decrease in the phylum and genus. The most relevant result was the lack of engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient's local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.
粪便微生物群移植（FMT）是一种有效的抗感染（CDI）方法，但在其他疾病（如溃疡性结肠炎（UC））中的效果仍不尽人意。受体对供体微生物群的黏膜免疫反应可能是 FMT 有效性的相关因素。我们的目的是设计并验证一种基于免疫的个体化测试，以优化 FMT 的粪便供体选择。首先，我们通过共培养器官捐献者尸体小肠黏膜获得的淋巴细胞（n=7）和来自 19 名健康供体粪便的微生物相关分子模式（MAMPs），验证了该测试。使用 Cytometric Bead Array 试剂盒（B&D）测定上清液中白细胞介素的含量来确定炎症反应。然后，我们对 4 例 UC 患者进行了临床试点研究，从直肠活检中提取免疫活性细胞，从 3 名供体候选者的 MAMPs 中提取。我们使用测试结果来指导 FMT 的供体选择，通过结肠镜检查进行，并在接下来的一个月内通过灌肠进行 4 次强化灌输。通过粪便 16S rDNA 大量测序评估微生物组的植入情况，并对患者进行 16 周的临床随访。结果表明，IL-6、IL-8 和 IL-1β是最具变异性的标志物，尽管我们观察到对微生物刺激的普遍耐受。16 周后，UC 患者的临床和结肠镜缓解并未实现，尽管 FMT 引发了门和属的富集，而门和属的减少。最相关的结果是 UC 中没有植入。总之，UC 患者 FMT 的临床成功似乎不受基于受体对 FMT 局部免疫反应的供体选择的影响，这表明该方法对此类患者的 FMT 粪便供体优化无效。
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