Impact of oral Chlamydia Vaccination on Host Gut Microbiome and Metabolites Composition

Chlamydia trachomatis, an intracellular pathogen, is recognized as the most common sexually transmitted bacterial infection among women worldwide. Chlamydia infections can lead to undesirable clinical outcomes, including pelvic inflammatory disease and infertility. Recently, the gut has been identified as a niche for Chlamydia colonization; however, despite the biological impact on the host remaining under investigation, oral inoculation of Chlamydia as a whole-organism vaccine has been reported as a promising strategy for preventing genital Chlamydia infections. Few studies have evaluated the impact of oral Chlamydia vaccination on the gut microbiome and metabolite changes. In this study, we assessed time-series alterations in the gut microbiome and metabolites following oral Chlamydia inoculation, 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 significantly different metabolites in the gut across various vaccination approaches during the 30-day immunization process. Additionally, we discussed potential biomarkers of effective immunization based on correlation analysis. IMPORTANCEChlamydia infections primarily lead to morbidity rather than mortality. Consequently, in developing and implementing a Chlamydia vaccine, the utmost priority is ensuring safety. As a promising yet controversial approach, live oral vaccination for Chlamydia raises concerns regarding its impact on the hosts gut environment. Our study not only investigates changes in the gut microbiome and metabolites during vaccination but also identifies potential biomarkers during immunization. These findings are crucial for the development of whole-organism oral Chlamydia vaccines and provide valuable insights into the long-term colonization of Chlamydia in the gut.