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

Abstract

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 .

Keywords: Gut microbiome; Infectious disease; Microbiome-drug interaction; Microbiome-parasite interaction; Praziquantel; Schistosoma mansoni.

Fig. 1

Composition of the microbiota of pre-treatment samples at two taxonomic levels. This bar chart shows the composition of the most abundant bacterial groups of each patient, both at the phylum level (a) as well as at the family level (b)

Fig. 2

The gut microbiome composition differences in samples collected from S. mansoni negative and positive children at baseline. a Quantitative representation of the differences in the gut microbial composition of both groups using a bar chart representation and an LDA model (P < 0.05). b Taxonomic representation of significantly different relative abundances. Discriminative features (P < 0.05) are observed at various taxonomic levels

Fig. 3

Indicators of microbial diversity in control and infected samples, both before and 24 hours after treatment. a Faith’s Phylogenetic Diversity indicator. b The absolute number of observed species. c The Shannon’s index. d The Chao 1 index

Fig. 4

Differences in the gut microbiota of children infected with S. mansoni after administration of placebo or praziquantel. This cladogram shows the differences in bacterial composition of infected children receiving a placebo treatment (= Placebo) or infected children with failed treatment receiving a unique dose of 60 mg/kg praziquantel (= Low)

Fig. 5

Comparison of microbiome in the treatment failures versus successful treatment groups. a Before administration of praziquantel. b 24 hours after administration of 60 mg/kg praziquantel. Using the same statistical tests did not reveal any differences of the same groups for the 3 weeks follow-up samples (data not shown)

Fig. 6

Fusobacterium spp. qPCR. a The copy number for Fusobacterium spp. before treatment both in cured and non-cured children. b The variation in copies number over the 24 hours post-treatment period in both cured and non-cured children