Mucosal interactions during Trichuris infections

The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T.muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes. PLOS ONE | DOI:10.1371/journal.pone. 0125495 May 5, 2015 1 / 22 OPEN ACCESS Citation: Holm JB, Sorobetea D, Kiilerich P, RamayoCaldas Y, Estellé J, Ma T, et al. (2015) Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli. PLoS ONE 10(5): e0125495. doi:10.1371/journal.pone. 0125495 Academic Editor: Irving Coy Allen, Virginia Tech University, UNITED STATES Received: January 26, 2015 Accepted: March 13, 2015 Published: May 5, 2015 Copyright: © 2015 Holm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All sequence data is available from the European Nucleotide Archive (ENA) with study accession number: PRJEB6560. Immunological raw data is available from Dryad Digital Repository (doi:10.5061/dryad.md0vg). Funding: This work was supported by grants from the Novo Nordisk Foundation (www. novonordiskfonden.dk), The Carlsberg Foundation (www.carlsbergfondet.dk), and the Swedish Medical Research Council (www.vr.se). Yuliaxis RamayoCaldas was funded by the European Union, in the framework of the Marie-Curie FP7 COFUND People