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Intestinal helminths are potent regulators of their host's immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions.

Intestinal parasitic worms (commonly named intestinal helminths) affect close to one quarter of the world population and cause major losses for the livestock industry. These parasites establish chronic infections by modulation the immunity of their host. The immune system of mammals has been challenged by this immuno-modulation all along the course of evolution. Although intestinal parasites constitute a threat to human health, their recent eradication from industrialized regions may not be without consequence. In fact, the loss of intestinal helminth-driven immuno-regulation has been proposed to underlie the increased frequency of immune disorders observed in developed areas. Here, we first showed that one immune-modulatory strategy of intestinal helminths involves alterations of the intestinal bacterial communities. Although a lot remained to be understood about these alterations, they were characterized by higher intestinal levels of short-chain fatty acids (SCFAs), bacterial metabolites with immuno-suppressive activity. A better understanding of how intestinal helminths modulate host immunity via the intestinal microbiome may open the door to novel strategies to fight both intestinal parasites and immune disorders. In this context, I further characterized the impact of intestinal helminths on fecal bacterial communities in children living in a rural region of Ecuador and naturally infected with Ascaris lumbricoides, a parasite affecting 1.2 billion people worldwide. I then used a mouse model to extensively characterize the impact of intestinal helminth infection on intestinal bacterial communities along the intestinal tract. Based on our main results, we hypothesized that the worm-induced mucus secretion may favor the growth of SCFA-producing bacteria in the intestine, which in turn down-regulates the host immunity by promoting regulatory T cells. As part of this work, I also developed a web-based platform to assist scientists in analyzing data from high-throughput nucleic-acid sequencing, a method commonly used to characterize microbial communities but for which data analysis remains particularly challenging.

The microbiota have been shown to play an important role in diverse biological processes including immunity, metabolism, and digestion. Assessing the exact composition of the microbiota has proven challenging due to the often unknown growth specificities of its members, and culture-based approaches typically fail to capture the complete diversity of microorganisms present. Next Generation Sequencing (NGS) methods provide an efficient means to gather information about cultured and uncultured members of the microbiota. This article provides a method to characterize bacterial communities in terms of species composition using high-throughput sequencing. Briefly, by extracting the entire DNA content of a microbiota sample and performing a targeted high-throughput sequencing of the 16S rRNA gene, a phylogenetic marker for prokaryotes, prediction of the composition of the entire bacterial community is made possible. © 2017 by John Wiley & Sons, Inc.