Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome.

Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome.
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DOI:
10.1186/s13071-018-2739-2
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发表时间:
2018-03-12
影响因子:
3.2
通讯作者:
Keiser J
Keiser J
中科院分区:
医学2区
文献类型:
--
作者:
Schneeberger PHH;Coulibaly JT;Panic G;Daubenberger C;Gueuning M;Frey JE;Keiser J

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血吸虫病是一种被忽视的热带疾病,给数百万人带来负担。一种名为吡喹酮的药物目前用于治疗和控制。临床上相关的耐药性尚未被描述,但治疗结果存在相当大的异质性,从治愈到只有中等的减卵率不等。这项研究的目的是调查蠕虫引起的肠道微生物区系的潜在菌群失调,并评估特定的微生物组特征是否会影响吡喹酮的反应。我们利用16S rRNA基因的V3和V4区,对34名科特迪瓦曼氏血吸虫感染和未感染儿童的肠道微生物区系进行了筛选。每个感染的儿童在服用60 mg/kg吡喹酮或安慰剂后,收集一份治疗前、一份24小时和一份21天的随访样本。总体分类特征和多样性指标被发现接近于所有儿童的“健康”肠道结构。在感染和未感染曼氏葡萄球菌的儿童之间,观察到轻微的总体成分变化。吡喹酮治疗与肠道分类图谱的重大变化无关,因此通过排除对肠道微生物的非靶标影响,从而加强了药物的良好安全性。无论是在基线还是治疗后24小时,治愈的个体中梭杆菌目的16S rRNA基因都明显更丰富。实时荧光定量聚合酶链式反应证实了梭杆菌的过量表达。在治愈的儿童中。梭杆菌属(Fus杆菌spp.)丰度也可能与处理诱导的曼氏血吸虫产卵减少相关。我们的研究表明,无论是曼氏沙门氏菌感染还是吡喹酮给药都不会对微生物组成产生显著影响,治疗前梭杆菌数量越多,吡喹酮治疗曼氏沙门氏菌感染的效果越好。国际标准随机对照试验,编号为ISRCTN15280205。本文的在线版本(10.1186/s13071-0182739-2)包含补充材料,可供授权用户使用。
Schistosomiasis is a neglected tropical disease burdening millions of people. One drug, praziquantel, is currently used for treatment and control. Clinically relevant drug resistance has not yet been described, but there is considerable heterogeneity in treatment outcomes, ranging from cure to only moderate egg reduction rates. The objectives of this study are to investigate potential worm-induced dysbacteriosis of the gut microbiota and to assess whether a specific microbiome profile could influence praziquantel response. Using V3 and V4 regions of 16S rRNA genes, we screened the gut microbiota of 34 Schistosoma mansoni infected and uninfected children from Côte d’Ivoire. From each infected child one pre-treatment, one 24-hour and one 21-day follow-up sample after administering 60 mg/kg praziquantel or placebo, were collected. Overall taxonomic profiling and diversity indicators were found to be close to a “healthy” gut structure in all children. Slight overall compositional changes were observed between S. mansoni-infected and non-infected children. Praziquantel treatment was not linked to a major shift in the gut taxonomic profiles, thus reinforcing the good safety profile of the drug by ruling out off-targets effects on the gut microbes.16S rRNA gene of the Fusobacteriales order was significantly more abundant in cured individuals, both at baseline and 24 hours post-treatment. A real-time qPCR confirmed the over-abundance of Fusobacterium spp. in cured children. Fusobacterium spp. abundance could also be correlated with treatment induced S. mansoni egg-reduction. Our study suggests that neither a S. mansoni infection nor praziquantel administration triggers a significant effect on the microbial composition and that a higher abundance of Fusobacterium spp., before treatment, is associated with higher efficacy of praziquantel in the treatment of S. mansoni infections. International Standard Randomised Controlled Trial, number ISRCTN15280205. The online version of this article (10.1186/s13071-018-2739-2) contains supplementary material, which is available to authorized users.
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发表时间: 2000-05-01
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