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Microbiota are active modulators of host biology and are implicated in the etiology of visceral hypersensitivity. Objectives: we studied the association between the circulating mRNA transcriptome, the intensity of induced visceral pain (IVP), and variation in the oral microbiome among participants with and without baseline visceral hypersensitivity. Methods: Transcriptomic profiles and microbial abundance were correlated with IVP intensity. Host mRNA and microbes associated with IVP were explored, linking variation in the microbiome to host RNA biology. Results: 259 OTUs were found to be associated with IVP through correlation to differential expression of 471 genes in molecular pathways related to inflammation and neural mechanisms, including Rho and PI3K\/AKT pathways. The bacterial families Lachnospiraceae, Prevotellaceae, and Veillonellaceae showed the highest degree of association. Oral microbial profiles with reduced diversity were characteristic of participants with visceral hypersensitivity. Conclusions: Our results suggest that the oral microbiome may be involved in systemic immune and inflammatory effects and play a role in nervous system and stem cell pathways. The interactions between visceral hypersensitivity, differentially expressed molecular pathways, and microbiota described here provide a framework for further work exploring the relationship between host and microbiome.<\/jats:p>","DOI":"10.3390\/nu17050921","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T09:59:17Z","timestamp":1741255157000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Host Transcriptome and Microbial Variation in Relation to Visceral Hyperalgesia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-0757","authenticated-orcid":false,"given":"Christopher J.","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Medicine, UConn Health, 263 Farmington Ave, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Prescott","sequence":"additional","affiliation":[{"name":"Inova Health Services, L.J. Murphy Children\u2019s Hospital, 3300 Gallows Rd, Falls Church, VA 22042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas H.","family":"Fourie","sequence":"additional","affiliation":[{"name":"National Institute of Nursing Research, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Abey","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimaging, National Institute of Alcohol Abuse and Alcoholism, 10 Center Drive, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LeeAnne B.","family":"Sherwin","sequence":"additional","affiliation":[{"name":"Sinclair School of Nursing, University of Missouri System, 915 Hitt Street, Columbia, MO 65203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9208-3004","authenticated-orcid":false,"given":"Bridgett","family":"Rahim-Williams","sequence":"additional","affiliation":[{"name":"Office of Research and Sponsored Programs, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-9622","authenticated-orcid":false,"given":"Paule V.","family":"Joseph","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 10 Center Drive, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4514-4772","authenticated-orcid":false,"given":"Hugo","family":"Posada-Quintero","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Storrs, CT 06269, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca K.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Laboratory of Innovative and Translational Nursing Research, School of Nursing, University of PA, 418 Curie Blvd, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-7118","authenticated-orcid":false,"given":"Wendy A.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Biobehavioral Health Sciences, School of Nursing, University of PA, 418 Curie Blvd, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1136\/gut.48.1.125","article-title":"Visceral hypersensitivity: Facts, speculations, and challenges","volume":"48","author":"Camilleri","year":"2001","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","article-title":"Central sensitization: A generator of pain hypersensitivity by central neural plasticity","volume":"10","author":"Latremoliere","year":"2009","journal-title":"J. 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