Schistosoma mansoni infection is associated with quantitative and qualitative modifications of the mammalian intestinal microbiota

Abstract

In spite of the extensive contribution of intestinal pathology to the pathophysiology of schistosomiasis, little is known of the impact of schistosome infection on the composition of the gut microbiota of its mammalian host. Here, we characterised the fluctuations in the composition of the gut microbial flora of the small and large intestine, as well as the changes in abundance of individual microbial species, of mice experimentally infected with Schistosoma mansoni with the goal of identifying microbial taxa with potential roles in the pathophysiology of infection and disease. Bioinformatic analyses of bacterial 16S rRNA gene data revealed an overall reduction in gut microbial alpha diversity, alongside a significant increase in microbial beta diversity characterised by expanded populations of Akkermansia muciniphila (phylum Verrucomicrobia) and lactobacilli, in the gut microbiota of S. mansoni-infected mice when compared to uninfected control animals. These data support a role of the mammalian gut microbiota in the pathogenesis of hepato-intestinal schistosomiasis and serves as a foundation for the design of mechanistic studies to unravel the complex relationships amongst parasitic helminths, gut microbiota, pathophysiology of infection and host immunity.

Figure 1

Bacteroidetes and Firmicutes are most abundant in the mouse gut microbiome. Relative abundances of bacterial phyla detected in luminal content samples from the small and large intestine of mice infected by Schistosoma mansoni (S+) at 28 and 50 days post-infection (D28 p.i. and D50 p.i., respectively), as well as of uninfected controls (S−). Percentages in individual pie chart sections indicate the relative proportion of the corresponding phylum.

Figure 2

Profound shifts in the gut microbial profiles of Schistosoma mansoni infected mice were observed at 50 days post-infection. The gut microbial profiles of luminal content samples from the small and large intestine of mice infected by S. mansoni (S+) at 28 and 50 days post-infection (D28 p.i. and D50 p.i., respectively), as well as of uninfected controls (S−), ordinated by Principal Coordinates Analysis (PCoA) (a: small intestine; b: large intestine) and Canonical Correspondence Analysis (CCA) (c: small intestine; d: large intestine).

Figure 3

Gut microbial shannon diversity was significantly reduced in Schistosoma mansoni infected mice at 50 days post-infection compared to uninfected controls. Differences between microbial Shannon diversity detected in the gut microbiota of mice infected with S. mansoni (S+) at day 28 and 50 post-infection (D28 p.i. and D50 p.i., respectively) and that of uninfected control mice (S−), in the small (a; SI) and large intestine (b; LI). Asterisks denote significant differences (P < 0.05) between individual groups.

Figure 4

Gut microbial beta diversity was significantly increased in Schistosoma mansoni infected mice 50 days post-infection compared to uninfected controls. Differences between microbial beta diversity detected in the gut microbiota of mice infected with S. mansoni (S+) at day 28 and 50 post-infection (D28 p.i. and D50 p.i., respectively) compared with control mice (S−), in the small (a; SI) and large intestine (b; LI). Asterisks denote significant differences (P < 0.05) between individual groups.

Figure 5

Bacterial taxa displaying significant differences in abundance between microbial profiles obtained from luminal content samples from mice experimentally infected with Schistosoma mansoni (S+) and uninfected controls (S−) based on linear discriminant analysis effect Size (LEfSe). For S+, datasets are separated for site (small and large intestine) and time point (28 and 50 days post-infection) and compared to the corresponding S− datasets. Colours correspond to Linear Discriminant Analysis (LDA) scores of 4.5 or higher (red), 4 to 4.5 (orange), and 3.5 to 4 (yellow).