Helminths and microbes within the vertebrate gut – not all studies are created equal

The multifaceted interactions occurring between gastrointestinal (GI) parasitic helminths and the host gut microbiota are emerging as a key area of study within the broader research domain of host-pathogen relationships. Over the past few years, a wealth of investigations has demonstrated that GI helminths interact with the host gut flora, and that such interactions result in modifications of the host immune and metabolic statuses. Nevertheless, whilst selected changes in gut microbial composition are consistently observed in response to GI helminth infections across several host-parasite systems, research in this area to date is largely characterised by inconsistent findings. These discrepancies are particularly evident when data from studies of GI helminth-microbiota interactions conducted in humans from parasite-endemic regions are compared. In this review, we provide an overview of the main sources of variance that affect investigations on human-helminth-gut microbiota interactions and propose a series of methodological approaches that, whilst accounting for the inevitable constraints of human fieldwork, are aimed at minimising confounding factors and draw biologically meaningful interpretations from highly variable datasets

First reports of autochthonous eyeworm infection by Thelazia callipaeda (Spirurida, Thelaziidae) in dogs and cat from France

Thelazia callipaeda (Spirurida, Thelaziidae) is a small nematode living in the conjunctival sac of domestic and wild carnivores, rabbits and humans causing lacrimation, epiphora, conjunctivitis, keratitis and even corneal ulcers. The first autochthonous cases of thelaziosis affecting four dogs and one cat living in South Western France (Dordogne area) are reported and described. Nematodes recovered from the animals were morphologically identified as T. callipaeda and a partial region of the cytochrome oxidase c subunit 1 gene (cox1) was amplified by PCR from nematode specimens (from two dogs and the cat). In each case, this was shown to have an identical sequence to the haplotype 1 (h1) of T. callipaeda. So far, the arthropod acting as intermediate host of T. callipaeda eyeworms has not been identified in France although it might be Phortica variegata (Steganinae, Drosophilidae) as recently described in Italy

Gastrointestinal worms and bacteria: From association to intervention

A plethora of studies, both experimental and epidemiological, have indicated the occurrence of associations between infections by gastrointestinal (GI) helminths and the composition and function of the host gut microbiota. Given the worldwide risk and spread of anthelmintic resistance, particularly for GI parasites of livestock, a better understanding of the mechanisms underpinning the relationships between GI helminths and the gut microbiome, and between the latter and host health, may assist the development of novel microbiome-targeting and other bacteria-based strategies for parasite control. In this article, we review current and prospective methods to manipulate the host gut microbiome, and/or to exploit the immune stimulatory and modulatory properties of gut bacteria (and their products) to counteract the negative impact of GI worm infections; we also discuss the potential applications of these intervention strategies in programmes aimed to aid the fight against helminth diseases of humans and livestock.Javier Sotillo is a Miguel Servet Fellow funded by Instituto de Salud Carlos III (CP17III/00002).S

The past, present, and future of Leishmania genomics and transcriptomics.

It has been nearly 10 years since the completion of the first entire genome sequence of a Leishmania parasite. Genomic and transcriptomic analyses have advanced our understanding of the biology of Leishmania, and shed new light on the complex interactions occurring within the parasite-host-vector triangle. Here, we review these advances and examine potential avenues for translation of these discoveries into treatment and control programs. In addition, we argue for a strong need to explore how disease in dogs relates to that in humans, and how an improved understanding in line with the 'One Health' concept may open new avenues for the control of these devastating diseases.Part of this article was conceived within the framework of of the EurNegVec COST Action TD1303. Funding from the Isaac Newton Trust/ Wellcome Trust ISSF/University of Cambridge Joint Research Grants Scheme to C.C. is gratefully acknowledged.This is the final version of the article. It originally appeared in Trends in Parasitology, Volume 31, Issue 3, p100–108, March 2015 doi: 10.1016/j.pt.2014.12.01

Suppression of inflammation by helminths: a role for the gut microbiota?

Multiple recent investigations have highlighted the promise of helminth-based therapies for the treatment of inflammatory disorders of the intestinal tract of humans, including inflammatory bowel disease and coeliac disease. However, the mechanisms by which helminths regulate immune responses, leading to the amelioration of symptoms of chronic inflammation are unknown. Given the pivotal roles of the intestinal microbiota in the pathogenesis of these disorders, it has been hypothesized that helminth-induced modifications of the gut commensal flora may be responsible for the therapeutic properties of gastrointestinal parasites. In this article, we review recent progress in the elucidation of host-parasite-microbiota interactions in both animal models of chronic inflammation and humans, and provide a working hypothesis of the role of the gut microbiota in helminth-induced suppression of inflammation.Funding from the Isaac Newton Trust / Wellcome Trust ISSF / University of Cambridge Joint Research Grants Scheme (C.C.) and the Australian National Health and Medical Research Council (NHMRC) grants 1037304, 1020114 (A.L.), 1052938 (C.C.) and 613718 (P.G.) is gratefully acknowledged.This is the final version of the article. It first appeared from Royal Society Publishing via http://dx.doi.org/10.1098/rstb.2014.029

Gastropod-Borne Helminths: A Look at the Snail-Parasite Interplay.

More than 300 million people suffer from a range of diseases caused by gastropod-borne helminths, predominantly flatworms and roundworms, whose life cycles are characterized by a diversified ecology and epidemiology. Despite the plethora of data on these parasites, very little is known of the fundamental biology of their gastropod intermediate hosts, or of the interactions occurring at the snail-helminth interface. In this article, we focus on schistosomes and metastrongylids of human and animal significance, and review current knowledge of snail-parasite interplay. Future efforts aimed at elucidating key elements of the biology and ecology of the snail intermediate hosts, together with an improved understanding of snail-parasite interactions, will aid to identify, plan, and develop new strategies for disease control focused on gastropod intermediate hosts.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.pt.2015.12.00

A bug’s life: Delving into the challenges of helminth microbiome studies

The body of vertebrates is inhabited by trillions of microorganisms, i.e. viruses, archaea, bacteria and unicellular eukaryotes, together referred to as the ‘microbiota’. Similarly, vertebrates also host a plethora of parasitic worms (the ‘macrobiota’), some of which share their environment with the microbiota inhabiting the gastrointestinal tract [1]. Complex interactions between the helminths and the gut microbiota have been associated with establishment of parasite infection, disease manifestations, and host immune-modulation [2, 3]. Remarkably, not only enteric helminths alter the 26 gut microbiome composition [4], but also the infection with blood flukes of the genus Schistosoma has been associated to intestinal dysbiosis even before the onset of egg laying [5, 6]. Comparably, over the last decade, evidence has emerged of the contribution(s) of the resident microbiota to several physiological and reproductive processes of invertebrate hosts, including insects, arachnids, worms and snails [7, 8]. These noteworthy discoveries, coupled with 30 the recent expansion of high-throughput microbiota- and microbiome-profiling approaches (the former referring to a community of microorganisms themselves, and the latter to the microorganisms and their genomes, in a ecological niche), are rapidly leading to a much better understanding of the composition and functions of microbial communities inhabiting parasitic worms of major public health and socio-economic significance. This basic knowledge might expose exploitable vulnerabilities of parasites, paving the way to the development of novel control strategies [9]

Tissue-specific transcriptomes of Anisakis simplex (sensu stricto) and Anisakis pegreffii reveal potential molecular mechanisms involved in pathogenicity.

Background: Larval stages of the sibling species of parasitic nematodes Anisakis simplex sensu stricto (AS) and Anisakis pegreffii (AP) are responsible for a fish-borne zoonosis, known as anisakiasis, that humans acquire via the ingestion of raw or undercooked infected fish or fish-based products. These two species differ in geographical distribution, genetic background and peculiar traits involved in pathogenicity. However, thus far, little is known of key molecules potentially involved in host-parasite interactions. Here, high-throughput RNA-Seq and bioinformatics analyses of sequence data were applied to the characterization of the whole sets of transcripts expressed by infective larvae of AS and AP, as well as of their pharyngeal tissues, in a bid to identify transcripts potentially involved in tissue invasion and host-pathogen interplay. Results: Approximately ~34,000,000 single-end reads were generated from cDNA libraries for each species. Transcripts identified in AS and AP encoded 19,403 and 10,424 putative peptides, respectively, and were classified based on homology searches, protein motifs, Gene Ontology and biological pathway mapping. Differential gene expression analysis yielded 226 and 339 transcripts up-regulated in the pharyngeal regions of AS and AP, respectively, compared with their corresponding whole-larvae datasets. These included proteolytic enzymes, molecules encoding anaesthetics, inhibitors of primary hemostasis and virulence factors, anticoagulants and immunomodulatory peptides. Conclusions: This work provides the scientific community with a list of key transcripts expressed by AS and AP pharyngeal tissues and corresponding annotation information which represents a ready-to-use resource for future functional studies of biological pathways specifically involved in host-parasite interplay

Comparative Transcriptomics Reveals Clues for Differences in Pathogenicity between Hysterothylacium aduncum, Anisakis simplex sensu stricto and Anisakis pegreffii.

Ascaridoid nematodes are widespread in marine fishes. Despite their major socioeconomic importance, mechanisms associated to the fish-borne zoonotic disease anisakiasis are still obscure. RNA-Seq and de-novo assembly were herein applied to RNA extracted from larvae and dissected pharynx of Hysterothylacium aduncum (HA), a non-pathogenic nematode. Assembled transcripts in HA were annotated and compared to the transcriptomes of the zoonotic species Anisakis simplex sensu stricto (AS) and Anisakis pegreffii (AP). Approximately 60,000,000 single-end reads were generated for HA, AS and AP. Transcripts in HA encoded for 30,254 putative peptides while AS and AP encoded for 20,574 and 20,840 putative peptides, respectively. Differential gene expression analyses yielded 471, 612 and 526 transcripts up regulated in the pharynx of HA, AS and AP. The transcriptomes of larvae and pharynx of HA were enriched in transcripts encoding collagen, peptidases, ribosomal proteins and in heat-shock motifs. Transcripts encoding proteolytic enzymes, anesthetics, inhibitors of primary hemostasis and virulence factors, anticoagulants and immunomodulatory peptides were up-regulated in AS and AP pharynx. This study represents the first transcriptomic characterization of a marine parasitic nematode commonly recovered in fish and probably of negligible concern for public health