Gastrointestinal nematodes (GINs), particularly Haemonchus contortus (H. contortus), pose significant challenges to small ruminant health and productivity, with increasing resistance to commercial anthelmintics. Conventional diagnostic techniques, such as fecal egg counts (FEC) and larval cultures (LC), are labor-intensive, time-consuming, and require technical expertise, limiting their practicality in field settings. There is an urgent need for faster, more accessible diagnostic tools to inform treatment decisions and improve parasite management strategies. In this study, we hypothesized that changes in microbiota, specifically shifts in microbial richness, community composition, and consistency, can serve as reliable biomarkers for infection and resistance. To test this hypothesis, we employed a metagenomic approach to characterize microbial communities in Alpine wethers based on their GIN infection status. Animals were divided into four groups: uninfected controls, infected-only, infected and treated with zoledronic acid (a bisphosphonate, previously believed to act as an antibiotic), and infected and treated with a neutralizing antibody targeting γδ T cells. Metagenomic analyses of tissue samples revealed distinct microbial signatures associated with host susceptibility or resistance. Infection with H. contortus was linked to inflammatory microbial profiles, which varied depending on the treatment and infection status. Our findings suggest that inflammation-associated microbial taxa could serve as indicators of parasitic infection, supporting the development of more precise, data-driven diagnostic tools for early detection of haemonchosis. Additionally, by identifying microbiota-based markers of resistance, this research paves the way for more sustainable parasite control strategies, including microbiota manipulation and fecal microbiota transplantation. Overall, metagenomics provides a robust framework for investigating host-pathogen interactions and uncovering novel approaches to combat parasitism in livestock.
References
[1]
Charlier, J., van der Voort, M., Kenyon, F., Skuce, P. and Vercruysse, J. (2014) Chasing Helminths and Their Economic Impact on Farmed Ruminants. Trends in Parasitology, 30, 361-367. https://doi.org/10.1016/j.pt.2014.04.009
[2]
Roeber, F., Morrison, A., Casaert, S., Smith, L., Claerebout, E. and Skuce, P. (2017) Multiplexed-tandem PCR for the Specific Diagnosis of Gastrointestinal Nematode Infections in Sheep: An European Validation Study. Parasites & Vectors, 10, Article No. 226. https://doi.org/10.1186/s13071-017-2165-x
[3]
Cai, K., Wang, F., Wang, K., Liu, J., Wang, B., Xu, Q., et al. (2017) In Vitro Predatory Activity of Arthrobotrys oligospora and after Passing through Gastrointestinal Tract of Small Ruminants on Infective Larvae of Trichostrongylides. Experimental Parasitology, 177, 104-111. https://doi.org/10.1016/j.exppara.2017.04.008
[4]
Fthenakis, G.C. and Menzies, P.I. (2011) Preface: Therapeutics and Control of Sheep and Goat Diseases. Veterinary Clinics of North America: Food Animal Practice, 27, xiii-xiv. https://doi.org/10.1016/j.cvfa.2010.11.001
[5]
Matthews, J.B., Geldhof, P., Tzelos, T. and Claerebout, E. (2016) Progress in the Development of Subunit Vaccines for Gastrointestinal Nematodes of Ruminants. Parasite Immunology, 38, 744-753. https://doi.org/10.1111/pim.12391
[6]
Hahn, M.A., Piecyk, A., Jorge, F., Cerrato, R., Kalbe, M. and Dheilly, N.M. (2022) Host Phenotype and Microbiome Vary with Infection Status, Parasite Genotype, and Parasite Microbiome Composition. Molecular Ecology, 31, 1577-1594. https://doi.org/10.1111/mec.16344
[7]
Tilahun, Y., Pinango, J.Q., Johnson, F., Lett, C., Smith, K., Gipson, T., et al. (2022) Transcript and Blood-Microbiome Analysis Towards a Blood Diagnostic Tool for Goats Affected by Haemonchus contortus. Scientific Reports, 12, Article No. 5362. https://doi.org/10.1038/s41598-022-08939-x
[8]
Elsheikha, H. (2017) Endoparasites in Cattle: Studies and Diagnostics. Vet Times, VT47.31.
[9]
Clézardin, P. (2013) Mechanisms of Action of Bisphosphonates in Oncology: A Scientific Concept Evolving from Antiresorptive to Anticancer Activities. BoneKEy Reports, 2, Article No. 267. https://doi.org/10.1038/bonekey.2013.1
[10]
Inagaki-Ohara, K., Sakamoto, Y., Dohi, T. and Smith, A.L. (2011) γδ T Cells Play a Protective Role during Infection with Nippostrongylus brasiliensis by Promoting Goblet Cell Function in the Small Intestine. Immunology, 134, 448-458. https://doi.org/10.1111/j.1365-2567.2011.03503.x
[11]
Mills, K.H.G. (2022) IL-17 and Il-17-Producing Cells in Protection versus Pathology. Nature Reviews Immunology, 23, 38-54. https://doi.org/10.1038/s41577-022-00746-9
[12]
Shrestha, N., Ida, J.A., Lubinski, A.S., Pallin, M., Kaplan, G. and Haslett, P.A.J. (2005) Regulation of Acquired Immunity by γδ T-Cell/Dendritic-Cell Interactions. Annals of the New York Academy of Sciences, 1062, 79-94. https://doi.org/10.1196/annals.1358.011
[13]
O’Keeffe, K.R., Halliday, F.W., Jones, C.D., Carbone, I. and Mitchell, C.E. (2021) Parasites, Niche Modification and the Host Microbiome: A Field Survey of Multiple Parasites. Molecular Ecology, 30, 2404-2416. https://doi.org/10.1111/mec.15892
[14]
Quince, C., Walker, A.W., Simpson, J.T., Loman, N.J. and Segata, N. (2017) Shotgun Metagenomics, from Sampling to Analysis. Nature Biotechnology, 35, 833-844. https://doi.org/10.1038/nbt.3935
Wieland Brown, L.C., Penaranda, C., Kashyap, P.C., Williams, B.B., Clardy, J., Kronenberg, M., et al. (2013) Production of α-Galactosylceramide by a Prominent Member of the Human Gut Microbiota. PLOS Biology, 11, e1001610. https://doi.org/10.1371/journal.pbio.1001610
[17]
Broderick, N.A. (2015) A Common Origin for Immunity and Digestion. Frontiers in Immunology, 6, Article 72. https://doi.org/10.3389/fimmu.2015.00072
[18]
Califf, K., Gonzalez, A., Knight, R. and Caporaso, J.G. (2014) The Human Micro-Biome: Getting Personal: Each of Us Harbors a Unique Microbiome, and Its Characteristics Play an Important Role in Differentiating Us from One Another. Microbe, 9, 410-415.
[19]
Huttenhower, C., Kostic, A.D. and Xavier, R.J. (2014) Inflammatory Bowel Disease as a Model for Translating the Microbiome. Immunity, 40, 843-854. https://doi.org/10.1016/j.immuni.2014.05.013
[20]
Maizels, R.M. and Yazdanbakhsh, M. (2003) Immune Regulation by Helminth Parasites: Cellular and Molecular Mechanisms. Nature Reviews Immunology, 3, 733-744. https://doi.org/10.1038/nri1183
[21]
Ingham, A., Reverter, A., Windon, R., Hunt, P. and Menzies, M. (2008) Gastrointestinal Nematode Challenge Induces Some Conserved Gene Expression Changes in the Gut Mucosa of Genetically Resistant Sheep. International Journal for Parasitology, 38, 431-442. https://doi.org/10.1016/j.ijpara.2007.07.012
[22]
Silva, M.V.B., Sonstegard, T.S., Hanotte, O., Mugambi, J.M., Garcia, J.F., Nagda, S., et al. (2011) Identification of Quantitative Trait Loci Affecting Resistance to Gastrointestinal Parasites in a Double Backcross Population of Red Maasai and Dorper Sheep. Animal Genetics, 43, 63-71. https://doi.org/10.1111/j.1365-2052.2011.02202.x
[23]
Balic, A., Bowles, V.M. and Meeusen, E.N.T. (2002) Mechanisms of Immunity to Haemonchus contortus Infection in Sheep. Parasite Immunology, 24, 39-46. https://doi.org/10.1046/j.0141-9838.2001.00432.x
