Deciphering the Coordinated Roles of Host Genome, Duodenal Mucosal Genes, and Microbiota in Regulating Complex Traits in Chicken

Deciphering the Coordinated Roles of Host Genome, Duodenal Mucosal Genes, and Microbiota in Regulating Complex Traits in Chicken | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Research Article Deciphering the Coordinated Roles of Host Genome, Duodenal Mucosal Genes, and Microbiota in Regulating Complex Traits in Chicken Fangren Lan, Qianqian Zhou, Xiaochang Li, Jiaming Jin, Wenxin Zhang, and 6 more https://doi.org/ 10.21203/rs.3.rs-3978613/v1 This work is licensed under a CC BY 4.0 License Video Script The complex interactions between host genetics and the gut microbiome are well recognized; however, the specific impact of gene expression pattern and microbial composition on each other remains to be further explored. Here we investigated this complex interplay within a sizable population of 705 hens, employing integrative analyses to examine the relationships among host genetics, mucosal gene expression, and the gut microbiota. Specific microbial taxa exhibited a strong adherence to the host genomic variants, particularly in the cecum such as the Christensenellaceae family with a heritability (h 2 ) of 0.365. We proposed a novel concept regulatability ( \({r}_{b}^{2}\) ), which was derived from h 2 , to quantify the cumulative effects of gene expression on the given phenotypes. The duodenal mucosal transcriptome emerged as a potent influencer of duodenal microbial taxa, with exceptionally higher \({r}_{b}^{2}\) values (0.17 ± 0.01, mean ± SE) compared to h 2 (0.02 ± 0.00). Through a comparative analysis of chickens and humans, we revealed similar average microbiability (m 2 ) values of 0.18 and 0.20, and significant distinctions in average \({r}_{b}^{2}\) values (0.17 vs 0.04). Notably, cis heritability ( \({h}_{cis}^{2}\) ) quantifies the impact of genetic variations proximal to a gene on its expression, while trans heritability ( \({h}_{trans}^{2}\) ) assesses the influence of distant genetic variations. Higher \({h}_{trans}^{2}\) values compared to \({h}_{cis}^{2}\) , and a greater prevalence of trans-regulated genes over cis-regulated ones underscored the significant role of loci outside the cis-window in shaping gene expression levels. Furthermore, our exploration into the regulation of duodenal mucosal genes and microbiota on 18 complex traits enhanced our understanding of their regulatory mechanism, in which gene CHST14 and its regulatory relationships with Lactobacillus salivarius jointly facilitated the deposition of abdominal fat. This study has enhanced our understanding of host-microbe dynamics, which helps to devise strategies to modulate host-microbe interactions for improving economic traits in chicken. Chickens Host genetics Gut microbiota Regulatability Integrative analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations No competing interests reported. Supplementary Files GraphicalAbstract.tif Graphic Abstract Host genome, hepatic and duodenal transcriptome and gut microbiome were integrated tounravel the regulatory mechanisms underlying the complex phenotypes in chickens. Heritability estimation and GWAS analysis from the aspect of genome, regulatability estimation from transcriptome and microbiability estimation from the aspect of microbiome were collectively performed on the host phenotypes. By integrating the genome and transcriptome, cis and trans heritability of genes were estimated, and methods like eQTL mapping and SMR were employed to uncover the genetic regulatory mechanisms of phenotypes. Integrating the genome and microbiome, we conducted the microbial heritability estimation and GWAS analysis to explore the extent to which the host genome shapes the microbiota. Integrating the transcriptome and microbiome, we estimated the microbiability of genes and the regulatability of microbiota, investigating the degree of interaction between host gene expression and gut microbiota. Combining all analytical methods mentioned above, a more advanced and comprehensive understanding of the extent and how host and microbiota interact to regulate the host phenotypes can be achieved. SupplementaryTables.xlsx SupplementaryFigureS1.tif Supplementary Fig. S1. Comparative analysis of gene expression patterns between liver and duodenum. (A) Visualization of the variance in gene expression between liver and duodenum based on PCA analysis. (B) Volcano plot identified differential expressed genes between liver and duodenum. (C) Top 20 significantly enriched biological processes in liver and duodenum. SupplementaryFigureS2.tif Supplementary Fig. S2. Spatial dynamics of microbial diversity and community composition across diverse gut segments in chickens. (A) The amount of taxa classified from phylum to species with high quality ASVs. (B) Alpha diversity based on the Shannon diversity index to determine significant differences (***p < 0.001). (C) Principal coordinate analysis (PCoA) plot generated using OTU metrics based on the Bray–Curtis dissimilarities. Each point represents a sample. (D) Relative abundance of the dominant microbial phyla in different gut segments. (E) Relative abundance of dominant genera in different gut segments. SupplementaryFigureS3.tif Supplementary Fig. S3. The cumulative relative abundances of microbial taxa with different detection rates in specific segment at family, genus and species levels. SupplementaryFigureS4.tif Supplementary Fig. S4. Circular Manhattan plots of GWAS for the microbial taxa in family Christensenellaceae, including family Christensenellaceae, genus Christensenellaceae R-7 group , species f_Christensenellaceae; g_uncultured , and species f_Christensenellaceae;g_uncultured;s_uncultured_bacterium . Blue and red dots indicate suggestively significant and significant SNPs, respectively. Cite Share Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3978613","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":274542675,"identity":"41dfcff5-a7e6-4f65-b741-5f9ce17f2aa5","order_by":0,"name":"Fangren Lan","email":"","orcid":"","institution":"State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Fangren","middleName":"","lastName":"Lan","suffix":""},{"id":274542676,"identity":"4ffeef8f-8476-43eb-b41f-b3e63f643752","order_by":1,"name":"Qianqian 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Wu","email":"","orcid":"","institution":"Beijing Engineering Research Centre of Layer","correspondingAuthor":false,"prefix":"","firstName":"Guiqin","middleName":"","lastName":"Wu","suffix":""},{"id":274542682,"identity":"9c94e98b-b579-4e0b-8cd0-3d905abc5339","order_by":7,"name":"Guangqi Li","email":"","orcid":"","institution":"Beijing Engineering Research Centre of Layer","correspondingAuthor":false,"prefix":"","firstName":"Guangqi","middleName":"","lastName":"Li","suffix":""},{"id":274542683,"identity":"88a72ae7-d1f5-4b58-8a30-02b0171b064a","order_by":8,"name":"Yiyuan Yan","email":"","orcid":"","institution":"Beijing Engineering Research Centre of Layer","correspondingAuthor":false,"prefix":"","firstName":"Yiyuan","middleName":"","lastName":"Yan","suffix":""},{"id":274542684,"identity":"033df8b3-4067-4be2-b824-0b18d6b54d05","order_by":9,"name":"Congjiao Sun","email":"","orcid":"","institution":"State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Congjiao","middleName":"","lastName":"Sun","suffix":""},{"id":274542685,"identity":"ac98ef4b-86d8-4d23-913f-2f175524581c","order_by":10,"name":"Ning Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYNCCCgglQYKWMyRrYWwjRYu5RPKzh1/n2ckbHGA+eJuHwS6PoBbLGWnmxrLbkg03HGBLtuZhSC4mqMXgRoKZtOS2A4wbDvCYSfMwHEhsIKwl/Zu05JwD9hsO8H8jVkuOmeTHhgOJQFvYiNRy5k2ZNMOx5OSZh9mMLecYJBOh5Xj6NskfNXa2fcebH954U2FHWAuDQAIDMw+IwQw2gaB6IOA/wMD4gxiFo2AUjIJRMHIBADtUOyKaNCCSAAAAAElFTkSuQmCC","orcid":"","institution":"State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University","correspondingAuthor":true,"prefix":"","firstName":"Ning","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-02-22 12:45:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3978613/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3978613/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40168-025-02054-5","type":"published","date":"2025-03-01T15:58:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":51675480,"identity":"f170daa9-af6c-4629-a905-becfa1e311a9","added_by":"auto","created_at":"2024-02-27 04:39:35","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4955507,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe shaping role of the host genome on the gut microbiota. \u003c/strong\u003e(\u003cstrong\u003eA\u003c/strong\u003e) Relationships between host genetic kinship and gut microbial similarities. (\u003cstrong\u003eB\u003c/strong\u003e) The amount and cumulative relative abundance of heritable microbial taxa in each sampling sites from family to species level. (\u003cstrong\u003eC\u003c/strong\u003e) The SNP-based heritability estimates of microbial taxa regulated by the host genome in multiple gut sites from family to species level.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/11bf06d4faef62719167c3d8.jpg"},{"id":51675488,"identity":"ef8c5407-ea67-4eaa-a8df-e622e677ff89","added_by":"auto","created_at":"2024-02-27 04:39:38","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5530245,"visible":true,"origin":"","legend":"\u003cp\u003eMicrobial genome-wide association studies in family (\u003cstrong\u003eA\u003c/strong\u003e), genus (\u003cstrong\u003eB\u003c/strong\u003e), species (\u003cstrong\u003eC\u003c/strong\u003e) levels. Microbial taxa are renamed according to the gut sites. For example, family Christensenellaceae in cecum is renamed by C_Christensenellaceae. The horizontal red and blue lines indicate genome-wide significance (P = 3.32×10\u003csup\u003e−7\u003c/sup\u003e) and suggestive significance (P = 6.63×10\u003csup\u003e−6\u003c/sup\u003e) thresholds in the Manhattan plot. Each point represents a SNP.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/30d8ffa70b53cf9553f9788b.jpg"},{"id":51675490,"identity":"a8f5beac-627a-4dde-9415-63042fe198f3","added_by":"auto","created_at":"2024-02-27 04:39:38","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":6513548,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eInteraction between host gene expression and duodenal microbiota. \u003c/strong\u003e(\u003cstrong\u003eA\u003c/strong\u003e) Procrustes analysis between the gene expression profile and duodenal microbial community. (\u003cstrong\u003eB\u003c/strong\u003e) Comparison of the heritability and microbiability of duodenal mucosal genes. (\u003cstrong\u003eC\u003c/strong\u003e) Heritability and regulatability estimations of duodenal microbiota from family to species level.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/14943e18ddd74e7eda07f30d.jpg"},{"id":51675491,"identity":"d1d0ffc0-001c-48e9-b8bb-3a53a1d8941a","added_by":"auto","created_at":"2024-02-27 04:39:38","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4349382,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparative analysis of host genetics and intestinal microbial interaction patterns between chicken and human. \u003c/strong\u003e(\u003cstrong\u003eA\u003c/strong\u003e) Procrustes analysis between colonic gene expression profile and microbial community in human. (\u003cstrong\u003eB\u003c/strong\u003e) Comparison of the regulatability estimates of microbial species between chicken and human. Shared taxa were specifically visualized. (\u003cstrong\u003eC\u003c/strong\u003e) Comparison of the microbiability estimates of mucosal genes between chicken and human.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/7f68b7e505cd6fd0e2c89b5b.jpg"},{"id":51675492,"identity":"ccbd1a87-ac02-428e-8d89-17061640075b","added_by":"auto","created_at":"2024-02-27 04:39:39","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2170136,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRelationships between genetics and gene expression. \u003c/strong\u003e(\u003cstrong\u003eA\u003c/strong\u003e) Correlation of the host genetic kinship and gene expression similarity in liver and duodenum. (\u003cstrong\u003eB\u003c/strong\u003e) Comparison of the \u003cem\u003eh\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003ecis\u003c/em\u003e and \u003cem\u003eh\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003etrans\u003c/em\u003e, and distribution of genes in different heritable patterns in liver and duodenum. (\u003cstrong\u003eC\u003c/strong\u003e) Statistics of hepatic and duodenal mucosal genes in different regulatory patterns categorized by chromosomes.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/26aea9fea620bd62734d11be.jpg"},{"id":51675486,"identity":"a258e3d7-c569-4f83-82f1-c7ac37ac782b","added_by":"auto","created_at":"2024-02-27 04:39:37","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":4823682,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eJoint contributions of duodenal mucosal genes and microbiota on the host phenotypes. \u003c/strong\u003e(\u003cstrong\u003eA\u003c/strong\u003e) Regulatory effect of duodenal mucosal genes on the host phenotypes and microbial taxa at species level. (\u003cstrong\u003eB\u003c/strong\u003e) Manhattan plots of GWAS for AFW and \u003cem\u003eLactobacillus salivarius\u003c/em\u003e. Gray, dark blue and reddish-brown dots indicate non-significant, suggestively significant and significant SNPs, respectively. Colocalization of trans-eQTLs of duodenal mucosal gene CHST14 identified two colocalized SNPs, highlighted by green diamonds. (\u003cstrong\u003eC\u003c/strong\u003e) The putative causal association between AFW and \u003cem\u003eL. salivarius\u003c/em\u003e generated by GSMR. (\u003cstrong\u003eD\u003c/strong\u003e) The summarized result of the relationship between CHST14, \u003cem\u003eL. salivarius\u003c/em\u003e and AFW. AFW: abdominal fat weight; AFP: abdominal fat percentage; BW90: body weight at the age of 90 weeks; LW: liver weight; LP: liver percentage; EN90: total egg number until the age of 90 weeks; FCR: feed conversion ratio; RFI: residual feed intake; HTG: hepatic triglyceride; HTBA: hepatic total bile acid; HDL: serum high-density lipoprotein; LDL: serum low-density lipoprotein; VLDL: serum very low-density lipoprotein; STG: serum triglyceride; STC: serum total cholesterol; HTBA: serum total bile acid.\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/28ca4d91418d74c17005242f.jpg"},{"id":77622658,"identity":"320b2c1a-5027-449b-88a6-5e9f46e8bbe7","added_by":"auto","created_at":"2025-03-03 16:09:00","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":29040234,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1_covered_7bc4a4a7-8690-4942-b6a1-361cb810d7f9.pdf"},{"id":51675484,"identity":"f6be674c-c7af-43b4-be0b-1cdb01d8c919","added_by":"auto","created_at":"2024-02-27 04:39:37","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2659452,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraphic Abstract\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHost genome, hepatic and duodenal transcriptome and gut microbiome were integrated tounravel the regulatory mechanisms underlying the complex phenotypes in chickens. Heritability estimation and GWAS analysis from the aspect of genome, regulatability estimation from transcriptome and microbiability estimation from the aspect of microbiome were collectively performed on the host phenotypes.\u003c/p\u003e\n\u003cp\u003eBy integrating the genome and transcriptome, cis and trans heritability of genes were estimated, and methods like eQTL mapping and SMR were employed to uncover the genetic regulatory mechanisms of phenotypes. Integrating the genome and microbiome, we conducted the microbial heritability estimation and GWAS analysis to explore the extent to which the host genome shapes the microbiota. Integrating the transcriptome and microbiome, we estimated the microbiability of genes and the regulatability of microbiota, investigating the degree of interaction between host gene expression and gut microbiota.\u003c/p\u003e\n\u003cp\u003eCombining all analytical methods mentioned above, a more advanced and comprehensive understanding of the extent and how host and microbiota interact to regulate the host phenotypes can be achieved.\u003c/p\u003e","description":"","filename":"GraphicalAbstract.tif","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/27a525f9a5fa3ac88409ca63.tif"},{"id":51675487,"identity":"bb98aa67-875e-4399-8f28-56b2fe4dc693","added_by":"auto","created_at":"2024-02-27 04:39:37","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":4257320,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/d72b1635d3b2cd9075818f60.xlsx"},{"id":51675482,"identity":"6593315a-01f0-40b0-81c4-d3b369c273f1","added_by":"auto","created_at":"2024-02-27 04:39:37","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":1538604,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. S1. Comparative analysis of gene expression patterns between liver and duodenum. \u003c/strong\u003e(\u003cstrong\u003eA\u003c/strong\u003e) Visualization of the variance in gene expression between liver and duodenum based on PCA analysis. (\u003cstrong\u003eB\u003c/strong\u003e) Volcano plot identified differential expressed genes between liver and duodenum. (\u003cstrong\u003eC\u003c/strong\u003e) Top 20 significantly enriched biological processes in liver and duodenum.\u003c/p\u003e","description":"","filename":"SupplementaryFigureS1.tif","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/20ebaf9ce8b31cf663394638.tif"},{"id":51675485,"identity":"3af9e30e-4b35-4690-9721-c0e3c07af42a","added_by":"auto","created_at":"2024-02-27 04:39:37","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":2967486,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. S2. Spatial dynamics of microbial diversity and community composition across diverse gut segments in chickens. \u003c/strong\u003e(\u003cstrong\u003eA\u003c/strong\u003e) The amount of taxa classified from phylum to species with high quality ASVs. (\u003cstrong\u003eB\u003c/strong\u003e) Alpha diversity based on the Shannon diversity index to determine significant differences (***p \u0026lt; 0.001). (\u003cstrong\u003eC\u003c/strong\u003e) Principal coordinate analysis (PCoA) plot generated using OTU metrics based on the Bray–Curtis dissimilarities. Each point represents a sample. (\u003cstrong\u003eD\u003c/strong\u003e) Relative abundance of the dominant microbial phyla in different gut segments. (\u003cstrong\u003eE\u003c/strong\u003e) Relative abundance of dominant genera in different gut segments.\u003c/p\u003e","description":"","filename":"SupplementaryFigureS2.tif","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/6576d72491299a74b47efa9e.tif"},{"id":51675483,"identity":"e8ba92ab-c85a-4d0d-be40-bd259dab3a44","added_by":"auto","created_at":"2024-02-27 04:39:37","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":441666,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. S3. \u003c/strong\u003eThe cumulative relative abundances of microbial taxa with different detection rates in specific segment at family, genus and species levels.\u003c/p\u003e","description":"","filename":"SupplementaryFigureS3.tif","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/a6f6cde9649baf8eb83093a6.tif"},{"id":51675489,"identity":"3d03c5b7-a3a1-4595-b0e0-b5cd50b5e1ee","added_by":"auto","created_at":"2024-02-27 04:39:38","extension":"tif","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":1911443,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. S4. \u003c/strong\u003eCircular Manhattan plots of GWAS for the microbial taxa in family Christensenellaceae, including family Christensenellaceae, genus \u003cem\u003eChristensenellaceae R-7 group\u003c/em\u003e, species \u003cem\u003ef_Christensenellaceae; g_uncultured\u003c/em\u003e, and species \u003cem\u003ef_Christensenellaceae;g_uncultured;s_uncultured_bacterium\u003c/em\u003e. Blue and red dots indicate suggestively significant and significant SNPs, respectively.\u003c/p\u003e","description":"","filename":"SupplementaryFigureS4.tif","url":"https://assets-eu.researchsquare.com/files/rs-3978613/v1/9a0d43f2861136f9d4850ae5.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Deciphering the Coordinated Roles of Host Genome, Duodenal Mucosal Genes, and Microbiota in Regulating Complex Traits in Chicken","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"microbiome","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mbio","sideBox":"Learn more about [Microbiome](http://microbiomejournal.biomedcentral.com/)","snPcode":"40168","submissionUrl":"https://submission.nature.com/new-submission/40168/3","title":"Microbiome","twitterHandle":"@MicrobiomeJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Chickens, Host genetics, Gut microbiota, Regulatability, Integrative analysis","lastPublishedDoi":"10.21203/rs.3.rs-3978613/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3978613/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe complex interactions between host genetics and the gut microbiome are well recognized; however, the specific impact of gene expression pattern and microbial composition on each other remains to be further explored. Here we investigated this complex interplay within a sizable population of 705 hens, employing integrative analyses to examine the relationships among host genetics, mucosal gene expression, and the gut microbiota. Specific microbial taxa exhibited a strong adherence to the host genomic variants, particularly in the cecum such as the Christensenellaceae family with a heritability (h\u003csup\u003e2\u003c/sup\u003e) of 0.365. We proposed a novel concept regulatability (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({r}_{b}^{2}\\)\u003c/span\u003e\u003c/span\u003e), which was derived from h\u003csup\u003e2\u003c/sup\u003e, to quantify the cumulative effects of gene expression on the given phenotypes. The duodenal mucosal transcriptome emerged as a potent influencer of duodenal microbial taxa, with exceptionally higher \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({r}_{b}^{2}\\)\u003c/span\u003e\u003c/span\u003e values (0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SE) compared to h\u003csup\u003e2\u003c/sup\u003e (0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00). Through a comparative analysis of chickens and humans, we revealed similar average microbiability (m\u003csup\u003e2\u003c/sup\u003e) values of 0.18 and 0.20, and significant distinctions in average \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({r}_{b}^{2}\\)\u003c/span\u003e\u003c/span\u003e values (0.17 vs 0.04). Notably, cis heritability (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({h}_{cis}^{2}\\)\u003c/span\u003e\u003c/span\u003e) quantifies the impact of genetic variations proximal to a gene on its expression, while trans heritability (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({h}_{trans}^{2}\\)\u003c/span\u003e\u003c/span\u003e) assesses the influence of distant genetic variations. Higher \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({h}_{trans}^{2}\\)\u003c/span\u003e\u003c/span\u003e values compared to \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({h}_{cis}^{2}\\)\u003c/span\u003e\u003c/span\u003e, and a greater prevalence of trans-regulated genes over cis-regulated ones underscored the significant role of loci outside the cis-window in shaping gene expression levels. Furthermore, our exploration into the regulation of duodenal mucosal genes and microbiota on 18 complex traits enhanced our understanding of their regulatory mechanism, in which gene CHST14 and its regulatory relationships with \u003cem\u003eLactobacillus salivarius\u003c/em\u003e jointly facilitated the deposition of abdominal fat. This study has enhanced our understanding of host-microbe dynamics, which helps to devise strategies to modulate host-microbe interactions for improving economic traits in chicken.\u003c/p\u003e","manuscriptTitle":"Deciphering the Coordinated Roles of Host Genome, Duodenal Mucosal Genes, and Microbiota in Regulating Complex Traits in Chicken","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-27 04:39:29","doi":"10.21203/rs.3.rs-3978613/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-03-05T15:06:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-05T15:05:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-23T16:58:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Microbiome","date":"2024-02-22T12:38:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"microbiome","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mbio","sideBox":"Learn more about [Microbiome](http://microbiomejournal.biomedcentral.com/)","snPcode":"40168","submissionUrl":"https://submission.nature.com/new-submission/40168/3","title":"Microbiome","twitterHandle":"@MicrobiomeJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"070ed84f-8fa6-4170-9fbf-583f8d1ab522","owner":[],"postedDate":"February 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-03T16:04:17+00:00","versionOfRecord":{"articleIdentity":"rs-3978613","link":"https://doi.org/10.1186/s40168-025-02054-5","journal":{"identity":"microbiome","isVorOnly":false,"title":"Microbiome"},"publishedOn":"2025-03-01 15:58:17","publishedOnDateReadable":"March 1st, 2025"},"versionCreatedAt":"2024-02-27 04:39:29","video":{"identity":"f3d6bcec0fc11b61f99e131c8619cecc"},"vorDoi":"10.1186/s40168-025-02054-5","vorDoiUrl":"https://doi.org/10.1186/s40168-025-02054-5","workflowStages":[]},"version":"v1","identity":"rs-3978613","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3978613","identity":"rs-3978613","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}