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溃疡性结肠炎患者接受供体粪便微生物群治疗后的噬菌体组揭示了与疾病缓解相关的标志物。

The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission.

机构信息

School of Biomedical Sciences, Faculty of Medicine and Health, UNSW, Sydney, Australia.

Concord Clinical School, University of Sydney, Sydney, Australia.

出版信息

Nat Commun. 2024 Oct 17;15(1):8979. doi: 10.1038/s41467-024-53454-4.

Abstract

Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution.

摘要

噬菌体在人类肠道微生物群中具有重要影响,但相对于细菌而言,它们的研究仍相对较少。这是粪便微生物群移植(FMT)研究的一个局限性,因为噬菌体可能会影响结果。在这里,我们使用宏基因组学对招募到的溃疡性结肠炎 FMT 两项双盲随机试验中的个体的噬菌体种群(噬菌体组)进行了分析。我们利用试验设计观察到噬菌体种群的行为与细菌种群相似,在健康状态下具有时间稳定性,在活跃疾病中出现失调,抗生素治疗和 FMT 可对其进行调节。我们鉴定出一种可能与疾病缓解相关的供体噬菌体,通过基因组分析发现它整合在一种被归类为 Oscillospiraceae 的细菌中,该细菌以前从一位百岁老人身上分离出来,并且预测除了 B12 之外还能产生维生素 B 复合物。我们的研究对不同状态下的噬菌体种群进行了深入评估,并表明噬菌体跟踪在确定疾病活动和缓解的决定因素方面具有实用价值。

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