Infection with a small intestinal helminth Heligmosomoides polygyrus bakeri consistently alters microbial communities throughout the small and large intestine

Abstract

Increasing evidence suggests that intestinal helminth infection can alter intestinal microbial communities with important impacts on the mammalian host. However, all of the studies to date utilize different techniques to study the microbiome and access different sites of the intestine with little consistency noted between studies. In the present study, we set out to perform a comprehensive analysis of the impact of intestinal helminth infection on the mammalian intestinal bacterial microbiome. For this purpose, we investigated the impact of experimental infection using the natural murine small intestinal helminth, Heligmosomoides polygyrus bakeri (Hpb) and examined possible alterations in both the mucous and luminal bacterial communities along the entire small and large intestine. We also explored the impact of common experimental variables, including the parasite batch and pre-infection microbiome, on the outcome of helminth-bacterial interactions. This work provides evidence that helminth infection reproducibly alters intestinal microbial communities – with an impact of infection noted along the entire length of the intestine. Although the exact nature of helminth-induced alterations to the intestinal microbiome differed depending on the parasite batch and microbiome community structure present prior to infection, changes extended well beyond the introduction of new bacterial species by the infecting larvae. Moreover, striking similarities between different experiments were noted, including the consistent outgrowth of a bacterium belonging to the Peptostreptococcaceae family throughout the intestine. Author Summary Increasing evidence indicates a role for interactions between intestinal helminths and the microbiome in regulating mammalian health, and a greater understanding of helminth-microbiota interactions may open the path for the development of novel immunomodulatory therapies. However, such studies are hampered by the inconsistent nature of the data reported so far. Such inconsistancies likely result from variations in the experimental and technological methodologies employed to investigate helminth-microbiota interactions and well has natural variation in the starting microbiome composition and/or worm genetics. We conducted a thorough study in which the reproducibility of helminth-induced alterations of microbial communities was determined and impact of common experimental variables – such as the starting microbiome and parasite batch - was determined. Our work reveals the robust ability of small intestinal helminth infection to alter microbial communities along the entire length of the intestine and additionally identifies a single bacterium that is strongly associated with infection across multiple experiments.

Infection with a small intestinal helminth, Heligmosomoides polygyrus bakeri, consistently alters microbial communities throughout the murine small and large intestine

“…Increased smooth muscle contractility together with increased epithelial cells secretions favor the eventual expulsion of adult worms from the intestinal lumen in a combined mechanism that is commonly referred to as the "weep and sweep" response (15) To date seven studies have investigated the possible interaction between Hpb and the intestinal microbiome (4,5,(16)(17)(18)(19)(20). The first of these used a method based on the generation of 16S clone libraries and Sanger sequencing to investigate the impact of infection of the bacterial communities and reported higher proportions of Lactobacillaceae in the ileum of infected mice (16). A later study, using real-time PCR and culture-based methods, reported differences between infected and non-infected mice in the bacterial communities residing in the ileum, the cecum and the colon at two weeks post infection (17).…”