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Selecting donors for fecal microbiota transplantation in ulcerative colitis
medRxiv - Gastroenterology Pub Date : 2020-07-07 , DOI: 10.1101/2020.03.25.20043182
Marcel A. de Leeuw , Manuel X. Duval

Background. Inflammatory bowel disease (IBD) is a set of conditions characterized by non-infectious chronic inflammation of the gastrointestinal tract. These primarily include Crohn's disease (CD), ulcerative colitis (UC) and indeterminate colitis. Fecal microbiota transplantation (FMT) has proven to be an effective treatment for some patients with active UC. There is currently no procedure allowing to predict the patients' response and to select the most adequate donor(s). Aim. Investigate microbiome characteristics in association with responder/non-responder status and develop selection criteria for donor samples to be used for UC FMT. Methods. Available UC longitudinal FMT microbiome data sets were in part combined and reanalyzed, with focus on species level changes in the microbiota, using state-of-the-art 16S analysis routines. Results. We predicted antibiotic resistance to be higher in non-responders (p=0.0064). Microbiomes of UC FMT responder donors have higher phylogenetic diversity (p=0.0026) and a higher proportion of facultative anaerobes (p=3.3E-5) as compared to non-responder donors. We predicted succinate and histamine to be increased in non-responder donors and non-responders, respectively. Sialic acid catabolism was also predicted to be increased in non-responder donors. Tryptamine and indole-3-acetaldehyde were predicted to be increased in responder donors. Conclusions. Our findings contribute to the establishment of selection criteria for UC FMT donor samples. Our results suggest that oxidative stress resistant facultative anaerobes are important for the establishment of an anaerobic environment and a successful UC FMT therapy. Several metabolites can be tested for additional prioritization of stool bank samples for UC FMT.

中文翻译:

溃疡性结肠炎的粪便微生物群移植选择供体

背景。炎症性肠病(IBD)是一组以胃肠道非感染性慢性炎症为特征的疾病。这些主要包括克罗恩氏病(CD),溃疡性结肠炎(UC)和不确定性结肠炎。粪便菌群移植(FMT)已被证明对某些活动性UC患者有效。当前尚无任何程序可以预测患者的反应并选择最合适的供体。目标。研究与响应者/非响应者状态相关的微生物组特征,并制定供UC FMT使用的供体样品的选择标准。方法。使用最新的16S分析例程,部分合并并重新分析了可用的UC纵向FMT微生物组数据集,重点是微生物群中物种水平的变化。结果。我们预测无反应者的抗生素耐药性会更高(p = 0.0064)。与非响应者相比,UC FMT响应者捐助者的微生物群具有更高的系统发育多样性(p = 0.0026)和兼性厌氧菌的比例更高(p = 3.3E-5)。我们预测琥珀酸和组胺分别在无反应者和无反应者中增加。唾液酸分解代谢也被预测在无反应的供体中增加。预计响应者供体中会增加色胺和吲哚-3-乙醛的含量。结论。我们的发现有助于建立UC FMT供体样品的选择标准。我们的结果表明,抗氧化应激的兼性厌氧菌对于建立厌氧环境和成功的UC FMT治疗很重要。
更新日期:2020-07-07
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