Gut microbiome predictors of treatment response and recurrence in primary Clostridium difficile infection.

Gut microbiome predictors of treatment response and recurrence in primary Clostridium difficile infection.
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DOI:
10.1111/apt.13750
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发表时间:
2016-10
影响因子:
7.6
通讯作者:
Kashyap P
Kashyap P
中科院分区:
医学1区
文献类型:
--
作者:
Khanna S;Montassier E;Schmidt B;Patel R;Knights D;Pardi DS;Kashyap P

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艰难梭菌感染(CDI)可能对最初的治疗无效并经常复发,但对应答和复发的预测是不一致的。决定CDI患者治疗反应和复发的肠道微生物区系的特定变化的影响尚不清楚。评估微生物特征作为CDI治疗反应和复发的预测因子。治疗前的粪便样本和临床元数据,包括结果,前瞻性地从首次CDI发作的患者中收集。使用MiSeq Illumina平台进行下一代16S rRNA测序,微生物群落结构的变化与CDI结果相关。纳入88例患者(中位年龄52.7岁,女性占60.2%)。治疗失败率为12.5%,反应后复发率为28.5%。与无反应的患者相比,对治疗有反应的患者有更多的瘤胃球菌科、Rikenellaceae、Clostridiaceae、Bacteroidae、Faecaliens和Rothia。根据这组微生物建立的风险指数区分应答者(平均值0.07±0.24)和无应答者(0.52±0.42;p=0.0002)。受试者操作特征(ROC)曲线显示风险指数是治疗反应的有力预测因子,曲线下面积(AUC)为0.85。在测试的临床参数中,只有使用质子泵抑制剂可以预测CDI的复发(OR 3.75,95%CI 1.27-11.1,p=0.01)。复发组与无复发组比较,韦氏杆菌、肠杆菌科、链球菌、类副杆菌和沙眼衣原体感染发生率显著增加,危险指数可预测复发(AUC=0.78)。肠道微生物区系特征预测治疗反应和复发,潜在地可以识别可能受益于早期替代治疗的CDI患者。
Clostridium difficile infection (CDI) may not respond to initial therapy and frequently recurs but predictors of response and recurrence are inconsistent. The impact of specific alterations in the gut microbiota determining treatment response and recurrence in patients with CDI is unknown. To assess microbial signatures as predictors of treatment response and recurrence in CDI. Pre-treatment stool samples and clinical metadata including outcomes were collected prospectively from patients with their first CDI episode. Next generation 16s rRNA sequencing using MiSeq Illumina platform was performed and changes in microbial community structure were correlated with CDI outcomes. Eighty-eight patients (median age 52.7 years, 60.2% female) were included. Treatment failure occurred in 12.5% and recurrence after response in 28.5%. Patients who responded to treatment had an increase in Ruminococcaceae, Rikenellaceae, Clostridiaceae, Bacteroides, Faecalibacterium and Rothia compared to non-responders. A risk-index built from this panel of microbes differentiated responders (mean 0.07±0.24) from non-responders (0.52±0.42; p=0.0002). Receiver operating characteristic (ROC) curve demonstrated that risk-index was a strong predictor of treatment response with an area under the curve (AUC) of 0.85. Among clinical parameters tested, only proton-pump inhibitor use predicted recurrent CDI (OR 3.75, 95%CI 1.27-11.1, p=0.01). Patients with recurrent CDI had statistically significant increases in Veillonella, Enterobacteriaceae, Streptococci, Parabacteroides and Lachnospiraceae compared to patients without recurrence and a risk index was able to predict recurrence (AUC=0.78). Gut microbiota signatures predict treatment response and recurrence potentially allowing identification of CDI patients that may benefit from early institution of alternate therapies.
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