Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus

Abstract

Background: In a murine model of inflammatory bowel disease (IBD), treatment of colitis in IL-10 gene-deficient mice with the parasitic helminth Heligmosomoides polygyrus ameliorates colonic inflammation. The cellular and molecular mechanisms driving this therapeutic host response are being studied vigorously. One proposed mechanism is that H. polygyrus infection favors the outgrowth or suppression of certain bacteria, which in turn help modulate host immunity.

Methods: To quantify the effect of H. polygyrus infection on the composition of the gastrointestinal (GI) tract microbiota, we conducted two independent microbial ecology analyses of C57BL/6 mice. We obtained and analyzed 3,353 bacterial 16S rRNA encoding gene sequences from the ileum and cecum of infected and uninfected mice as well as incective H. polygyrus larvae at the outset of the second experiment and adult worms taken directly from the mouse duodenum at the end of the second experiment.

Results: We found that a significant shift in the abundance and relative distribution of bacterial species in the ileum of mice is associated with H. polygyrus infection. Members of the bacterial family Lactobacillaceae significantly increased in abundance in the ileum of infected mice reproducibly in two independent experiments despite having different microbiotas present at the outset of each experiment.

Conclusions: These data support the concept that helminth infection shifts the composition of intestinal bacteria. The clinical consequences of these shifts in intestinal flora are yet to be explored.

Figure 1

Overview of two independent murine infection experiments. The difference between the first experiment (A) and the second (B) was the inclusion of the L3 larval stage and adult H. polygyrus worms.

Figure 2

Principal coordinates analysis of the structure of the GI tract microbiotas of H. polygyrus infected and uninfected mice. Cecal and ileal microbiotas are represented by symbols of different color (cecum = black, ileum = red); experiment 1 and 2 are represented by symbols of different shape (square = experiment 1, circle = experiment 2); and microbiotas from infected and uninfected mice are represented by filled and unfilled symbols (uninfected = unfilled, infected = filled). Cecal microbiotas grouped according to the experiments. Ileal microbiotas from infected mice were different from uninfected mice in both experiments.

Figure 3

Abundance of bacterial families in microbiotas from the first (A) and second (B) experiments. Samples are represented by differently colored bars (see legend). Error bars represent the standard deviation in abundance among the mice. No differences were detected between infected and uninfected cecal samples. Significant differences between the infected and uninfected ileal samples are indicated with asterisks and bolded bacterial family name.

Figure 4

Worm-associated microbiotas. Pie charts display the proportion of bacterial families in sequences from the L3 larvae (28 sequences), adult worms from infected mice (473 sequences), and samples from the ileum of mice (422 sequences). On average, the microbiota associated with adult worms is highly similar to the microbiota from ileal tissue samples.