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Recently, the gut has been identified as a niche for\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      colonization in human gut-derived organoids. However, despite the biological impact on the host remaining under investigation, oral inoculation of\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      as a whole-organism vaccine has been reported as a promising strategy for preventing genital\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      infections in mice. Few studies have evaluated the impact of oral\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      vaccination on the gut microbiome and metabolite changes. In this study, we assessed time-series alterations in the gut microbiome and metabolites following oral\n                      <jats:italic toggle=\"yes\">Chlamydia muridarum<\/jats:italic>\n                      inoculation in a mice model, and we analyzed the composition and correlation between serum immune parameters and the sequencing profiles in the host. We identified 129 microbial changes and 186 differentially abundant metabolites in the gut across various vaccination approaches during the 30-day immunization process. Additionally, we discussed the potential influence of live\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      on gut epithelium and the biomarkers of effective immunization based on correlation analysis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        infections primarily lead to morbidity rather than mortality. Consequently, in developing and implementing a\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        vaccine, the utmost priority is evaluation of safety. As a promising yet controversial approach, live oral vaccination for\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        raises concerns regarding its impact on the host\u2019s gut environment. Our study not only investigates changes in the gut microbiome and metabolites during vaccination but also identifies changes in gut epithelium during vaccination and potential biomarkers during immunization. These findings are crucial for the development of whole-organism oral\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        vaccines and provide valuable insights into the long-term colonization of\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        in the gut.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.01285-25","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T14:00:23Z","timestamp":1762783223000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Impact of oral\n                    <i>Chlamydia<\/i>\n                    vaccination on host gut microbiome and metabolite composition"],"prefix":"10.1128","volume":"10","author":[{"given":"Youyou","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Affiliated Maternal and Child Health Care Hospital, Hengyang Medical School, University of South China (Hunan Provincial Maternal and Child Health Care Hospital)","place":["Changsha, China"]},{"name":"National Health Commission Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Affiliated Maternal and Child Health Care Hospital, Hengyang Medical School, University of South China (Hunan Provincial Maternal and Child Health Care Hospital)","place":["Changsha, 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