Impact of oral <i>Chlamydia</i> vaccination on host gut microbiome and metabolite composition

<i>Chlamydia trachomatis</i>, an intracellular pathogen, is recognized as the most common sexually transmitted bacterial infection among women worldwide. <i>Chlamydia</i> infections can lead to undesirable clinical outcomes, including pelvic inflammatory disease and infertility. Recently, the gut has been identified as a niche for <i>Chlamydia</i> colonization in human gut-derived organoids. However, despite the biological impact on the host remaining under investigation, oral inoculation of <i>Chlamydia</i> as a whole-organism vaccine has been reported as a promising strategy for preventing genital <i>Chlamydia</i> infections in mice. Few studies have evaluated the impact of oral <i>Chlamydia</i> vaccination on the gut microbiome and metabolite changes. In this study, we assessed time-series alterations in the gut microbiome and metabolites following oral <i>Chlamydia muridarum</i> 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 <i>Chlamydia</i> on gut epithelium and the biomarkers of effective immunization based on correlation analysis.IMPORTANCE<i>Chlamydia</i> infections primarily lead to morbidity rather than mortality. Consequently, in developing and implementing a <i>Chlamydia</i> vaccine, the utmost priority is evaluation of safety. As a promising yet controversial approach, live oral vaccination for <i>Chlamydia</i> raises concerns regarding its impact on the host's 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 <i>Chlamydia</i> vaccines and provide valuable insights into the long-term colonization of <i>Chlamydia</i> in the gut.