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Knowledge of how the host responds to infection and how the parasite, in combination with microbiota, modulates host immunity can guide selection decisions to breed animals with improved parasite resistance. This understanding will help refine management practices and advance the development of new therapeutics for long-term helminth control.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Eggs per gram (EPG) of feces were obtained from Morada Nova sheep subjected to two artificial infections with <jats:italic>H. contortus<\/jats:italic> and used as a proxy to select animals with high resistance or susceptibility for transcriptome sequencing (RNA-seq) of the abomasum and 50\u00a0K single-nucleotide genotyping. Additionally, RNA-seq data for <jats:italic>H. contortus<\/jats:italic> were generated, and amplicon sequence variants (ASV) were obtained using polymerase chain reaction amplification and sequencing of bacterial and archaeal 16S ribosomal RNA genes from sheep feces and rumen content.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The heritability estimate for EPG was 0.12. <jats:italic>GAST<\/jats:italic>, <jats:italic>GNLY<\/jats:italic>, <jats:italic>IL13<\/jats:italic>, <jats:italic>MGRN1<\/jats:italic>, <jats:italic>FGF14<\/jats:italic>, and <jats:italic>RORC<\/jats:italic> genes and transcripts were differentially expressed between resistant and susceptible animals. A genome-wide association study identified regions on chromosomes 2 and 11 that harbor candidate genes for resistance, immune response, body weight, and adaptation. <jats:italic>Trans<\/jats:italic>-expression quantitative trait loci were found between significant variants and differentially expressed transcripts. Functional co-expression modules based on sheep genes and ASVs correlated with resistance to <jats:italic>H. contortus<\/jats:italic>, showing enrichment in pathways of response to bacteria, immune and inflammatory responses, and hub features of the <jats:italic>Christensenellaceae<\/jats:italic>, <jats:italic>Bacteroides<\/jats:italic>, and <jats:italic>Methanobrevibacter<\/jats:italic> genera; <jats:italic>Prevotellaceae<\/jats:italic> family; and <jats:italic>Verrucomicrobiota<\/jats:italic> phylum. In <jats:italic>H. contortus<\/jats:italic>, some mitochondrial, collagen-, and cuticle-related genes were expressed only in parasites isolated from susceptible sheep.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The present study identified chromosome regions, genes, transcripts, and pathways involved in the elaborate interactions between the sheep host, its gastrointestinal microbiota, and the <jats:italic>H. contortus<\/jats:italic> parasite. These findings will assist in the development of animal selection strategies for parasite resistance and interdisciplinary approaches to control <jats:italic>H. contortus<\/jats:italic> infection in sheep.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s13071-024-06205-9","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T15:02:48Z","timestamp":1709305368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multi-omics data elucidate parasite-host-microbiota interactions and resistance to Haemonchus contortus in sheep"],"prefix":"10.1186","volume":"17","author":[{"given":"Simone Cristina M\u00e9o","family":"Niciura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tain\u00e3 Figueiredo","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Mercia Guaratini","family":"Ibelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia Hiromi","family":"Okino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Gabriel","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda Vieira","family":"Benavides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina de Souza","family":"Chagas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Novita","family":"Esteves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro Pelegrine","family":"Minho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Correia de Almeida","family":"Regitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Gondro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"6205_CR1","doi-asserted-by":"publisher","DOI":"10.1590\/s1984-29612022044","volume":"31","author":"ACS Chagas","year":"2022","unstructured":"Chagas ACS, Tupy O, Santos IB, Esteves SN. 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