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

BACKGROUND: 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 c...

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Autores principales: Schneeberger, Pierre H. H., Coulibaly, Jean T., Panic, Gordana, Daubenberger, Claudia, Gueuning, Morgan, Frey, Jürg E., Keiser, Jennifer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848565/
https://www.ncbi.nlm.nih.gov/pubmed/29530088
http://dx.doi.org/10.1186/s13071-018-2739-2
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author Schneeberger, Pierre H. H.
Coulibaly, Jean T.
Panic, Gordana
Daubenberger, Claudia
Gueuning, Morgan
Frey, Jürg E.
Keiser, Jennifer
author_facet Schneeberger, Pierre H. H.
Coulibaly, Jean T.
Panic, Gordana
Daubenberger, Claudia
Gueuning, Morgan
Frey, Jürg E.
Keiser, Jennifer
author_sort Schneeberger, Pierre H. H.
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, number ISRCTN15280205. ELECTRONIC SUPPLEMENTARY MATERIAL: 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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spelling pubmed-58485652018-03-21 Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome Schneeberger, Pierre H. H. Coulibaly, Jean T. Panic, Gordana Daubenberger, Claudia Gueuning, Morgan Frey, Jürg E. Keiser, Jennifer Parasit Vectors Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, number ISRCTN15280205. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2739-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-12 /pmc/articles/PMC5848565/ /pubmed/29530088 http://dx.doi.org/10.1186/s13071-018-2739-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Schneeberger, Pierre H. H.
Coulibaly, Jean T.
Panic, Gordana
Daubenberger, Claudia
Gueuning, Morgan
Frey, Jürg E.
Keiser, Jennifer
Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome
title Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome
title_full Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome
title_fullStr Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome
title_full_unstemmed Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome
title_short Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome
title_sort investigations on the interplays between schistosoma mansoni, praziquantel and the gut microbiome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848565/
https://www.ncbi.nlm.nih.gov/pubmed/29530088
http://dx.doi.org/10.1186/s13071-018-2739-2
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