Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia.
Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia.
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DOI：
10.1371/journal.pntd.0006620
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发表时间：
2018-08
影响因子：
3.8
通讯作者：
Yazdanbakhsh M
中科院分区：
文献类型：
--
作者：
Martin I;Djuardi Y;Sartono E;Rosa BA;Supali T;Mitreva M;Houwing-Duistermaat JJ;Yazdanbakhsh M
微生物组研究表明，人体肠道微生物组和土壤传播的蠕虫之间存在相互作用。在驱虫时，驱虫药、蠕虫和微生物组组成之间可能会发生复杂的相互作用。为了剖析这一点，我们分析了在印度尼西亚一个土壤传播蠕虫流行地区进行的一项双盲安慰剂对照试验的样本中肠道细菌图谱所发生的变化。
在一年半的时间里，每三个月给予安慰剂或阿苯达唑。在最后一轮治疗之前和之后3个月评估蠕虫感染情况。对150名受试者使用454焦磷酸测序对细菌进行了图谱分析。在治疗前进行横断面统计分析以评估感染的影响，并在治疗后使用狄利克雷 - 多项回归模型确定感染和治疗对微生物组组成的影响。
在门水平上，治疗前，蠕虫感染和未感染受试者之间在微生物组组成的相对丰度方面没有差异，治疗后，阿苯达唑组和安慰剂组之间在微生物组组成方面也没有发现差异。然而，在仍然感染的受试者中，接受阿苯达唑和安慰剂的受试者在微生物组组成上存在显著差异。这种差异主要归因于拟杆菌门的改变。阿苯达唑对蛔虫和钩虫更有效，但对鞭虫无效，因此在接受阿苯达唑后仍然感染的受试者中，蠕虫组成以鞭虫为主。
我们发现，总体而言，阿苯达唑不影响微生物组组成。然而，治疗和蠕虫之间存在相互作用，因为在接受阿苯达唑且仍然感染的受试者中，拟杆菌门有显著改变。这种蠕虫 - 阿苯达唑相互作用需要进一步研究，以充分理解驱虫对微生物组影响的复杂性。
ISRCTN登记处，ISRCTN83830814。
随着土壤传播的蠕虫病和肠道微生物群都被认为在各种炎症性疾病中调节免疫系统，研究它们之间的关系变得越来越重要。然而，先前关于蠕虫对微生物组影响的研究结果并不一致。在这项研究中，进行了一项优化设计的安慰剂对照驱虫试验，以剖析蠕虫和驱虫治疗对肠道微生物图谱的影响。此外，使用了一种新的统计模型，通过应用多变量分析考虑细菌类别之间的相关结构来分析关联，从而不需要进行多重检验校正。
Microbiome studies suggest the presence of an interaction between the human gut microbiome and soil-transmitted helminth. Upon deworming, a complex interaction between the anthelminthic drug, helminths and microbiome composition might occur. To dissect this, we analyse the changes that take place in the gut bacteria profiles in samples from a double blind placebo controlled trial conducted in an area endemic for soil transmitted helminths in Indonesia. Either placebo or albendazole were given every three months for a period of one and a half years. Helminth infection was assessed before and at 3 months after the last treatment round. In 150 subjects, the bacteria were profiled using the 454 pyrosequencing. Statistical analysis was performed cross-sectionally at pre-treatment to assess the effect of infection, and at post-treatment to determine the effect of infection and treatment on microbiome composition using the Dirichlet-multinomial regression model. At a phylum level, at pre-treatment, no difference was seen in microbiome composition in terms of relative abundance between helminth-infected and uninfected subjects and at post-treatment, no differences were found in microbiome composition between albendazole and placebo group. However, in subjects who remained infected, there was a significant difference in the microbiome composition of those who had received albendazole and placebo. This difference was largely attributed to alteration of Bacteroidetes. Albendazole was more effective against Ascaris lumbricoides and hookworms but not against Trichuris trichiura, thus in those who remained infected after receiving albendazole, the helminth composition was dominated by T. trichiura. We found that overall, albendazole does not affect the microbiome composition. However, there is an interaction between treatment and helminths as in subjects who received albendazole and remained infected there was a significant alteration in Bacteroidetes. This helminth-albendazole interaction needs to be studied further to fully grasp the complexity of the effect of deworming on the microbiome. ISRCTN Registy, ISRCTN83830814. Studying the relationship between soil-transmitted helminthiasis and gut microbiota is becoming more important as both have been implicated in modulating immune system in various inflammatory diseases. However, findings of previous studies of the effect of helminth on the microbiome are inconsistent. In this study, an optimal design, a placebo-controlled anthelminthic trial was conducted to dissect the effect of helminths and anthelminthic treatment on gut microbial profile. In addition, a novel statistical model was used to analyse the association by taking into account the correlation structures between bacterial categories by applying multivariate analysis whereby the multiple testing correction is not needed.
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影响因子：
3.7
作者：
Lin AY;Almeida JP;Bear A;Liu N;Luo L;Foster AE;Drezek RA
通讯作者：
Drezek RA
影响因子：
15.5
作者：
Rosa BA;Supali T;Gankpala L;Djuardi Y;Sartono E;Zhou Y;Fischer K;Martin J;Tyagi R;Bolay FK;Fischer PU;Yazdanbakhsh M;Mitreva M
通讯作者：
Mitreva M
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
3.1
作者：
Li, Robert W.;Wu, Sitao;Urban, Joseph F., Jr.
通讯作者：
Urban, Joseph F., Jr.
影响因子：
0.8
作者：
Hall, Nancy S.
通讯作者：
Hall, Nancy S.