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This study aimed to evaluate the impact of a highly leukotoxic <jats:italic>Aggregatibacter actinomycetemcomitans<\/jats:italic> (<jats:italic>Aa<\/jats:italic>) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight\u2010week\u2010old male C57BL6 mice were divided into control (<jats:italic>n<\/jats:italic>\u2009=\u200916) and JP2 groups (<jats:italic>n<\/jats:italic>\u2009=\u200919), which received intragastric gavage with PBS and with a suspension of <jats:italic>Aa<\/jats:italic> JP2 (HK921), respectively, twice a week for 4\u2009weeks. Colonic <jats:italic>lamina propria<\/jats:italic>, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non\u2010parametric tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in <jats:italic>Aa<\/jats:italic> JP2\u2010infected mice than in controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). In contrast, infected animals showed higher abundance of <jats:italic>Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium<\/jats:italic>, higher levels of IL\u20106 expression in colonic tissues, and higher splenic MPO activity than controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL\u20106 levels than controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on this model, intragastric administration of <jats:italic>Aa<\/jats:italic> JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live\/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro\u2010inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13288","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T05:25:30Z","timestamp":1715923530000},"page":"961-973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Periodontal pathogen <i>Aggregatibacter actinomycetemcomitans<\/i><scp>JP2<\/scp> correlates with colonic leukocytes decrease and gut microbiome imbalance in mice"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2170-7940","authenticated-orcid":false,"given":"Andr\u00e9 L. 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