Editorial to Temporal Gut Microbial Changes Predict Recurrent Clostridium difficile Infection in Patients With and Without Ulcerative Colitis.

Editorial to Temporal Gut Microbial Changes Predict Recurrent Clostridium difficile Infection in Patients With and Without Ulcerative Colitis.
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颞部肠道微生物变化预测患有和不患有溃疡性结肠炎的患者复发艰难梭菌感染的社论。

DOI:
10.1093/ibd/izz336
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发表时间:
2020
影响因子:
4.9
通讯作者:
Kelsen,JudithR
Kelsen,JudithR
中科院分区:
医学2区
文献类型:
--
作者:
Conrad,MaireA;Kelsen,JudithR

文献摘要

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艰难梭菌感染率(CDI)在过去20年中急剧上升,已成为全球公共卫生威胁。它是主要的卫生保健相关感染之一,在北美是一个重大的经济负担。症状从轻微到严重的腹泻,中毒的巨结肠,甚至死亡。2、3 CDI发生的危险因素较多,均可导致肠道菌群失调或改变。炎症性肠病(IBD)患者尤其容易发生CDI和复发CDI(RCDI)。4、5 IBD患者CDI的临床表现可能不典型,包括年龄较小、缺乏抗生素暴露和社区发病。IBD患者感染的后遗症可能包括中毒性巨结肠、败血症、结肠切除术和死亡。6此外,这些患者有潜在IBD恶化的风险,CDI可以将疾病的发展轨迹从静止状态改变为严重状态。7目前,还没有一致的生物标志物来预测严重感染和CDI复发的风险。识别RCDI的预测因素及其对IBD病程的影响可能为患者提供预防和治疗策略。许多研究人员问,肠道微生物组中是否存在可重复的生物失调特征,最终可用于预测这些结果。虽然已经取得了一些进展,但由于肠道中细菌、病毒、真菌和其他微生物组成的复杂群落,我们才开始表征和了解其动态作为疾病的衡量标准,以及调整这一生态系统是否能带来有效的治疗方法。8在这一期的炎症性肠病中,Lee等人的手稿通过探索RCDI患者的微生物特征来解决这一挑战。作者对患有和不伴有溃疡性结肠炎的成人CDI患者的粪便细菌群落进行了一项单中心、前瞻性、观察性研究。他们的目的是调查是否有微生物生物标志物预测CDI的未来复发或CDI后UC的后续恶化。重要的是,作者设计这项研究是为了区分CDI和IBD对微生物区系的作用,因此纳入了CDI而没有IBD的受试者和没有CDI的UC受试者。这项研究是对IBD CDI领域的一次及时而重要的补充,在IBD中,确定疾病复发的进展可能是困难的。对57名受试者进行前瞻性跟踪,并将其分为3组,包括(1)32名UC合并CDI患者,(2)14名单纯CDI患者,以及(3)11名UC加重但无CDI患者。在46名CDI活跃的受试者中,46%的受试者有复发性CDI,32名UC受试者中有11名发展为随后的UC恶化。使用16S测序,作者能够通过冗余分析确定RCDI患者与研究期间未复发患者的粪便微生物区系总体上的社区差异。使用每个随访时间点的Jensen-Shannon距离,他们试图进一步澄清这一点,并确定具体的预测因素。在为期2周的抗生素疗程结束时,所有样本都与基线样本不同,RCDI和那些没有复发的患者之间没有发现差异。然而,在最后的时间点,即抗生素治疗后14天,患有RCDI的受试者与他们的基线样本比没有复发的受试者更不同。作者假设,与…相比,在他们指定为肠道重建时间点的这个时间点,将会有持续的生物失调
The rate of Clostridium difficile infection (CDI) has dramatically increased over the last 2 decades and has emerged as a global public health threat. It is one of the leading health care–associated infections and is a significant economic burden in North America. 1 Symptoms range from mild to severe diarrhea, toxic megacolon, or even death. 2, 3 There are many risk factors for the development of CDI, all which lead to dysbiosis or alterations in the intestinal microbiome. Patients with inflammatory bowel disease (IBD) are particularly at risk for CDI and recurrent CDI (rCDI). 4, 5 The clinical presentation of CDI in patients with IBD can be atypical, including presenting at a younger age, a lack of antibiotic exposure, and community onset. The sequelae of infection in patients with IBD can include toxic megacolon, sepsis, colectomy, and death. 6 In addition, these patients are at risk for exacerbation of their underlying IBD, and CDI can change the trajectory of the disease from quiescent to severe. 7 Currently, there are no consistent biomarkers to predict severe infection and risk of recurrent CDI. Identification of predictors of rCDI and its effect on the disease course of IBD may provide insight into preventative and therapeutic strategies for patients. Many investigators have asked whether there are reproducible signatures of dysbiosis in the gut microbiome that can ultimately serve to predict these outcomes. Although some progress has been made, due to the intestine’s complex community of bacteria, viruses, fungi, and other microorganisms, we have only begun to characterize and understand its dynamics as a measure of disease and whether modulation of this ecosystem can lead to effective therapeutic approaches. 8 In this issue of Inflammatory Bowel Diseases, the manuscript by Lee et al addresses this challenge by exploring the microbial signatures in patients with rCDI. The authors performed a single-center, prospective, observational study of the fecal bacterial community in adults with CDI with and without ulcerative colitis. They aimed to investigate if there are microbial biomarkers predictive of future recurrence of CDI or subsequent UC exacerbation after CDI. Importantly, the authors designed the study in an attempt to distinguish the roles of CDI and IBD on the microbiota and therefore included subjects with CDI without IBD and UC without CDI. This study is a timely and important addition to the field of CDI in IBD, in which determining disease progression from recurrence can be difficult.Fifty-seven subjects were followed prospectively and divided into 3 cohorts, including (1) 32 subjects with UC and CDI,(2) 14 with CDI alone, and (3) 11 with UC exacerbation without CDI. Of the 46 subjects with active CDI, 46% had recurrent CDI, and 11 of the 32 subjects with UC developed subsequent UC exacerbation. Using 16S sequencing, the authors were able to identify overall community differences by redundancy analysis in the fecal microbiota of patients with rCDI compared with those with no recurrence during the study. Using the Jensen-Shannon distance at each follow-up time point, they sought to clarify this further and to identify specific predictors. There were no differences seen between rCDI and those without recurrence at the end of the 2-week antibiotic course, where all samples were dissimilar from their baseline samples. However, at the final time point, 14 days postantibiotic treatment, the subjects with rCDI were more dissimilar from their baseline samples than those without recurrence. The authors hypothesized that at this time point, which they designated as the gut reconstitution time point, there would be ongoing dysbiosis as compared with those …