The relationship between bacterial communities and their host is being extensively investigated for the potential to improve the host’s health. Little is known about the interplay between the microbiota of parasites and the health of the infected host. Using nematode co-infection of lambs as a proof-of-concept model, the aim of this study was to characterise the microbiomes of nematodes and that of their host, enabling identification of candidate nematode-specific microbiota member(s) that could be exploited as drug development tools or for targeted therapy. Deep sequencing techniques were used to elucidate the microbiomes of different life stages of two parasitic nematodes of ruminants, Haemonchus contortus and Teladorsagia circumcincta, as well as that of the co-infected ovine hosts, pre- and post infection. Bioinformatic analyses demonstrated significant differences between the composition of the nematode and ovine microbiomes. The two nematode species also differed significantly. The data indicated a shift in the constitution of the larval nematode microbiome after exposure to the ovine microbiome, and in the ovine intestinal microbial community over time as a result of helminth co-infection. Several bacterial species were identified in nematodes that were absent from their surrounding abomasal environment, the most significant of which included Escherichia coli/Shigella. The ability to purposefully infect nematode species with engineered E. coli was demonstrated in vitro, validating the concept of using this bacterium as a nematode-specific drug development tool and/or drug delivery vehicle. To our knowledge, this is the first description of the concept of exploiting a parasite’s microbiome for drug development and treatment purposes.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $53.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Torgerson PR, Devleesschauwer B, Praet N, Speybroeck N, Willingham AL, Kasuga F, et al. World health organization estimates of the global and regional disease burden of 11 foodborne parasitic diseases, 2010: a data synthesis. PLoS Med. 2015;12:e1001920.
Kenyon F, Hutchings F, Morgan-Davies C, van Dijk J, Bartley DJ. Worm control in livestock: bringing science to the field. Trends Parasitol. 2017;33:669–77.
Rose H, Rinaldi L, Bosco A, Mavrot F, de Waal T, Skuce P, et al. Widespread anthelmintic resistance in European farmed ruminants: a systematic review. Vet Rec. 2015;176:546.
Peachey LE, Pinchbeck GL, Matthews JB, Burden FA, Behnke JM, Hodgkinson JE. Papaya latex supernatant has a potent effect on the free-living stages of equid cyathostomins in vitro. Vet Parasitol. 2016;228:23–9.
Hogan G, Tangney M. The Who, What, and Why of Drug Discovery and Development. Trends Pharmacol Sci. 2018;39:848–52.
Partridge FA, Murphy EA, Willis NJ, Bataille CJ, Forman R, Heyer-Chauhan N, et al. Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo. PLoS Negl Trop Dis. 2017;11:e0005359.
Partridge FA, Forman R, Willis NJ, Bataille CJR, Murphy EA, Brown AE, et al. 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm. PLoS Negl Trop Dis. 2018;12:e0006487.
Zaiss MM, Harris NL. Interactions between the intestinal microbiome and helminth parasites. Parasite Immunol. 2016;38:5–11.
White EC, Houlden A, Bancroft AJ, Hayes KS, Goldrick M, Grencis RK, et al. Manipulation of host and parasite microbiotas: Survival strategies during chronic nematode infection. Sci Adv. 2018;4:eaap7399.
Glendinning L, Nausch N, Free A, W Taylor D, Mutapi F. The microbiota and helminths: sharing the same niche in the human host. Parasitology. 2014;141:1255–71.
Rosa BA, Supali T, Gankpala L, Djuardi Y, Sartono E, Zhou Y, et al. Differential human gut microbiome assemblages during soil-transmitted helminth infections in Indonesia and Liberia. Microbiome. 2018;6:33.
Dirksen P, Marsh SA, Braker I, Heitland N, Wagner S, Nakad R, et al. The native microbiome of the nematode Caenorhabditis elegans: gateway to a new host-microbiome model. BMC Biol. 2016;14:38.
El-Ashram S, Suo X. Exploring the microbial community (microflora) associated with ovine Haemonchus contortus (macroflora) field strains. Sci Rep. 2017;7:70.
Meyer JM, Baskaran P, Quast C, Susoy V, Rodelsperger C, Glockner FO, et al. Succession and dynamics of Pristionchus nematodes and their microbiome during decomposition of Oryctes borbonicus on La Reunion Island. Environmental Microbiol. 2017;19:1476–89.
Derycke S, De Meester N, Rigaux A, Creer S, Bik H, Thomas WK, et al. Coexisting cryptic species of the Litoditis marina complex (Nematoda) show differential resource use and have distinct microbiomes with high intraspecific variability. Mol Ecol. 2016;25:2093–110.
Schuelke T, Pereira TJ, Hardy SM, Bik HM. Nematode-associated microbial taxa do not correlate with host phylogeny, geographic region or feeding morphology in marine sediment habitats. Mol Ecol. 2018;27:1930–51.
Paramsothy S, Kamm MA, Kaakoush NO, Walsh AJ, van den Bogaerde J, Samuel D, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017;389:1218–28.
Biddle AS. An In Vitro Model of the Horse Gut Microbiome Enables Identification of Lactate-Utilizing Bacteria That Differentially Respond to Starch Induction. PloS One. 2013;8:e77599.
Schallig HD. Immunological responses of sheep to Haemonchus contortus. Parasitol. 2000;120:Suppl:S63–72.
Harfoot CG. Anatomy, physiology and microbiology of the ruminant digestive tract. Prog Lipid Res. 1978;17:1–19.
Patterson DM, Jackson F, Huntley JF, Stevenson LM, Jones DG, Jackson E, et al. Studies on caprine responsiveness to nematodiasis: segregation of male goats into responders and non-responders. Int J Parasitol. 1996;26:187–94.
MAFF. Ministry of Agriculture, Fisheries and Food, Manual of veterinary parasitological laboratory techniques, 3rd edition. Her Majesty’s Stationary Office (HMSO), London, 1986. Reference Book 418.
Bancroft JD, Gamble M. Theory and practice of histological techniques. London: Churchill Livingstone; 2008.
Callahan BJ, McMurdie PJ, Holmes SP. Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. ISME J. 2017;11:2639–43.
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
Eisenhofer R, Minich JJ, Marotz C, Cooper A, Knight R, Weyrich LS. Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations. Trends Microbiol. 2019;27:105–17.
Glendinning L, Nausch N, Free A, Taylor DW, Mutapi F. The microbiota and helminths: sharing the same niche in the human host. Parasitology. 2014;141:1255–71.
Wang J, Fan H, Han Y, Zhao J, Zhou Z. Characterization of the microbial communities along the gastrointestinal tract of sheep by 454 pyrosequencing analysis. Asian-Australasian J Anim Sci. 2017;30:100–10.
Zeng Y, Zeng D, Ni X, Zhu H, Jian P, Zhou Y, et al. Microbial community compositions in the gastrointestinal tract of Chinese Mongolian sheep using Illumina MiSeq sequencing revealed high microbial diversity. AMB Express. 2017;7:75.
Chen L, Cai Y, Zhou G, Shi X, Su J, Chen G, et al. Rapid Sanger sequencing of the 16S rRNA gene for identification of some common pathogens. PloS One. 2014;9:e88886.
Pester M, Bittner N, Deevong P, Wagner M, Loy AA. ‘rare biosphere’ microorganism contributes to sulfate reduction in a peatland. ISME J. 2010;4:1591–602.
Slatko BE, Luck AN, Dobson SL, Foster JM. Wolbachia endosymbionts and human disease control. Mol Biochem Parasitol. 2014;195:88–95.
Murray J, Smith WD. Ingestion of host immunoglobulin by three non-blood-feeding nematode parasites of ruminants. Res Vet Sci. 1994;57:387–9.
Lello J, McClure SJ, Tyrrell K, Viney ME. Predicting the effects of parasite co-infection across species boundaries. Proc Biol Sci. 2018;285:1–9.
Murphy L, Pathak AK, Cattadori IM. A co-infection with two gastrointestinal nematodes alters host immune responses and only partially parasite dynamics. Parasite Immunol. 2013;35:421–32.
Almeida FA, Bassetto CC, Amarante MRV, Albuquerque ACA, Starling RZC, Amarante A. Helminth infections and hybridization between Haemonchus contortus and Haemonchus placei in sheep from Santana do Livramento, Brazil. J Vet Parasitol. 2018;27:280–8.
Lee SC, Tang MS, Lim YA, Choy SH, Kurtz ZD, Cox LM, et al. Helminth colonization is associated with increased diversity of the gut microbiota. PLoS Negl Trop Dis. 2014;8:e2880.
Telfer S, Lambin X, Birtles R, Beldomenico P, Burthe S, Paterson S, et al. Species interactions in a parasite community drive infection risk in a wildlife population. Science. 2010;330:243–6.
Goossens B, Osaer S, Kora S, Jaitner J, Ndao M, Geerts S. The interaction of Trypanosoma congolense and Haemonchus contortus in Djallonke sheep. Int J Parasitol. 1997;27:1579–84.
Kenyon F, Sargison ND, Skuce PJ, Jackson F. Sheep helminth parasitic disease in south eastern Scotland arising as a possible consequence of climate change. Veterinary Parasitol. 2009;163:293–7.
Li RW, Li W, Sun J, Yu P, Baldwin RL, Urban JF. The effect of helminth infection on the microbial composition and structure of the caprine abomasal microbiome. Sci Rep. 2016;6:20606.
El-Ashram S, Al Nasr I, Abouhajer F, El-Kemary M, Huang G, Dincel G, et al. Microbial community and ovine host response varies with early and late stages of Haemonchus contortus infection. Vet Res Commun. 2017;41:263–77.
Kamke J, Kittelmann S, Soni P, Li Y, Tavendale M, Ganesh S, et al. Rumen metagenome and metatranscriptome analyses of low methane yield sheep reveals a Sharpea-enriched microbiome characterised by lactic acid formation and utilisation. Microbiome. 2016;4:56.
Biavati B, Mattarelli P. Bifidobacterium ruminantium sp. nov. and Bifidobacterium merycicum sp. nov. from the rumens of cattle. Int J Syst Bacteriol. 1991;41:163–8.
Henderson G, Cox F, Ganesh S, Jonker A, Young W, Global Rumen Census C, et al. Rumen microbial community composition varies with diet and host, but a core microbiome is found across a wide geographical range. Sci Rep. 2015;5:14567.
Menon R, Ramanan V, Korolev KS. Interactions between species introduce spurious associations in microbiome studies. PLOS Comput Biol. 2018;14:e1005939.
Kaplan RM. Drug resistance in nematodes of veterinary importance: a status report. Trends Parasitol. 2004;20:477–81.
Fernandes MAM, Gilaverte S, Bianchi MD, da Silva CJA, Molento MB, Reyes FGR, et al. Moxidectin residues in tissues of lambs submitted to three endoparasite control programs. Res Vet Sci. 2017;114:406–11.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.
Prilassnig M, Wenisch C, Daxboeck F, Feierl G. Are probiotics detectable in human feces after oral uptake by healthy volunteers? Wien Klin Wochenschr. 2007;119:456–62.
Joeres-Nguyen-Xuan TH, Boehm SK, Joeres L, Schulze J, Kruis W. Survival of the probiotic Escherichia coli Nissle 1917 (EcN) in the gastrointestinal tract given in combination with oral mesalamine to healthy volunteers. Inflamm Bowel Dis. 2010;16:256–62.
Flores Bueso Y, Lehouritis P, Tangney M. In situ biomolecule production by bacteria; a synthetic biology approach to medicine. J Control Release. 2018;275:217–28.
Wassenaar TM. Insights from 100 Years of Research with Probiotic E. Coli. European J Microbiol & Immunol. 2016;6:147–61.
Murphy C, Rettedal E, Lehouritis P, Devoy C, Tangney M. Intratumoural production of TNFalpha by bacteria mediates cancer therapy. PLoS One. 2017;12:e0180034.
Lehouritis P, Stanton M, McCarthy FO, Jeavons M, Tangney M. Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria. J Control Release. 2016;222:9–17.
Cronin M, Le Boeuf F, Murphy C, Roy DG, Falls T, Bell JC, et al. Bacterial-mediated knockdown of tumor resistance to an oncolytic virus enhances therapy. Mol Ther. 2014;22:1188–97.
Byrne WL, Murphy CT, Cronin M, Wirth T, Tangney M. Bacterial-mediated DNA delivery to tumour associated phagocytic cells. J Control Release. 2014;196:384–93.
Lehouritis P, Hogan G, Tangney M. Designer bacteria as intratumoural enzyme biofactories. Adv Drug Deliv Rev. 2017;118:8–23.
The authors acknowledge the provision of in vitro larval images with kind permission from Prof Antony Page, University of Glasgow. MT acknowledges relevant support from Science Foundation Ireland (15/CDA/3630 and 12/RC/2273). We also gratefully acknowledge funding from The Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). We are grateful to the Bioservices Division, Moredun Research Institute, for expert care and assistance with the animals.
Conflict of interest
The authors declare that they have no conflict of interest.
All experimental procedures described here were approved by the Moredun Research Animal Welfare and Ethical Review Body and were conducted under the legislation of a UK Home Office License (reference P95890EC1) in accordance with the Animals (Scientific Procedures) Act of 1986.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.