Periodontal pathogen Aggregatibacter actinomycetemcomitans JP2 correlates with colonic leukocytes decrease and gut microbiome imbalance in mice.

AIM: Evidence suggests that translocation of oral pathogens through the oral-gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice. METHODS: Eight-week-old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, 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-parametric tests. RESULTS: The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2-infected mice than in controls (p < .05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL-6 expression in colonic tissues, and higher splenic MPO activity than controls (p < .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-6 levels than controls (p < .05). CONCLUSION: Based on this model, intragastric administration of Aa 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-inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.

Oral-gut bacterial profiles discriminate between periodontal health and diseases.

OBJECTIVE: This investigation explored oral-gut microbial signatures with potential to distinguish among periodontal conditions. BACKGROUND DATA: The interplay between the oral and gut microbiomes may be a critical pathway linking periodontal diseases and systemic inflammatory disorders. The mechanisms by which oral microorganisms translocate to the gut and cause microbial dysbiosis, favoring an inflammatory state, are still unknown. As a first approach, characterization of oral-gut microbial profiles associated with periodontal health and diseases can provide insights on such mechanisms of etiology and pathogenesis. METHODS: Fecal and saliva samples from individuals with periodontal health (PH, 8), gingivitis (GG, 17), and periodontitis (PD, 24) were analyzed for their microbial composition by 16S rRNA gene sequencing. Microbial taxa were compared and correlated to periodontal parameters. Multivariate discriminant analysis (MDA) was carried out to identify profiles related to health and disease. RESULTS: Few significant differences in oral-gut taxa were detected among clinical groups, although increase in fecal Fusobacterium nucleatum ss vincentii and salivary Aggregatibacter actinomycetemcomitans, Parvimonas micra, and Fretibacterium sp. HMT358 were strongly correlated with deep pockets and inflammation (p < .01). Over 50% of the fecal microbiota comprised microorganisms shared between oral and gut sites, whereas oral taxa were detected in approximately 9%, particularly enriched in GG fecal samples (p = .04). Trends for lower fecal richness and higher salivary diversity in PD compared to PH were observed. MDA was able to classify correctly 82% of the patients into the clinical groups. Main classifiers of periodontitis were high BMI, older age, and enrichment of oral-fecal Leptotrichia sp. HMT4, Peptostreptococcus stomatis, Dialister invisus, and a novel Lautropia sp. HMTC89-like organism. CONCLUSION: Within the limitations of an exploratory investigation, specific profiles of oral-gut taxa, including known and potential novel organisms, combined with social-demographic features were able to discriminate individuals with periodontal diseases in this study population.

Impact of systemic probiotics as adjuncts to subgingival instrumentation on the oral-gut microbiota associated with periodontitis: A randomized controlled clinical trial.

BACKGROUND: The oral-gut axis may be a route linking periodontal and systemic diseases. Probiotics could be an alternative for the treatment of microbial dysbiotic conditions, including periodontitis. This randomized placebo-controlled clinical trial evaluated the short-term efficacy of systemic probiotics adjunctive to subgingival instrumentation (SI) in promoting a better restoration of the oral-gut microbiotas and greater periodontal clinical outcome. METHODS: Systemically healthy adults with untreated periodontitis were recruited from a Dental School setting and allocated to receive SI plus placebo (n = 24) or probiotics (n = 24), one capsule/day for 30 days. Subgingival biofilm and stool were obtained at baseline and 2-months post-therapy for microbiological analyses by checkerboard and 16S rRNA gene sequencing. Differences in all parameters between placebo (n = 23) and probiotics (n = 19) groups were assessed by non-parametric tests. RESULTS: Most subgingival species and α-diversity decreased after therapies (P <0.05), whereas gut composition/diversity were slightly or not affected by treatments. In parallel, significant clinical improvement (P <0.05) was similar between groups, although a trend for a higher proportion of poor responders in the placebo (60.8%) than the probiotic group (31.5%) was observed (P = 0.07). Strong correlations between oral and fecal species were found (P <0.01), and distinct species related to poor response for different therapies (P <0.05). Patients were classified into five periodontitis oral-gut microbial clusters, which correlated differently with attachment loss after therapies (P <0.05). CONCLUSION: Systemic probiotics combined with SI did not provide short-term additional clinical or microbiological benefits in the treatment of periodontitis; however, response to therapies seemed to correlate with distinct oral-gut microbial profiles.