Tokyo Dental College

Animal studies suggest that periodontopathic bacteria induce gut dysbiosis and related pathology, possibly connecting periodontitis to non-oral diseases. However, the effects on the gut ecosystem in periodontitis patients are not fully understood.

We conducted a comprehensive analysis of the salivary and gut microbiota using 16S rRNA sequencing in periodontitis patients before and after treatment, comparing them to healthy participants. Serum metabolites were also analyzed.

Periodontitis patients showed high alpha diversity in both salivary and gut microbiota with a strong correlation. Significant differences were also observed in the gut microbiota composition between patients before treatment and healthy participants, irrespective of the ectopic colonization of periodontitis-associated bacteria in the gut. Co-abundance group analysis demonstrated that the gut microbiota of healthy participants was enriched with short-chain fatty acid producers. Changes in the gut microbiota coincided with alterations in the serum metabolite profile. While periodontal therapy improved salivary microbiota, it did not significantly affect gut microbiota.

Gut dysbiosis of periodontitis patients may impact systemic metabolite profiles. Given that periodontal therapy alone did not substantially improve the gut microbiota, adjunctive strategies targeting the gut microbiome may be effective in reducing the risk of periodontitis-associated diseases.

Median mandibular cyst is defined as an odontogenic cyst in a rare midline location. In spite of this definition, there have been two reports of a peculiar lesion, so-called “ciliated” median mandibular cyst associated with vital teeth, the origin of which cannot be explained in terms of odontogenic epithelium multipotentiality. We describe a thorough profile of an additional example. On the basis of the cone-beam computed tomography images of a wide open cavity in the midline of the lingual bone, the surgical findings of no association with the vital incisor roots, the immunophenotypes of the excretory duct epithelium and the absence of oncogenic mutations, the present “ciliated” median mandibular cyst associated with vital teeth may be an artifact caused by impingement of the lingual bone due to pedicled extension from an extra-glandular salivary duct cyst in the anterior mouth floor. Awareness of this ectopic presentation is of clinical importance for the differential diagnosis of radiolucencies in the median mandible.

Ectopic calcification is an abnormal regenerative response occurring in various tissues following injury, surgery, or genetic mutations. However, its underlying mechanisms remain unclear. By comparing three macrophage depletion methods using clodronate liposome, Csf1r neutralizing antibody, and macrophage-specific Csf1r gene deletion (Csf1r cKO), we found that F4/80(+)Csf1r(-) macrophages were specifically increased in calcified muscles in notexin-injected mice and BaCl₂-injected Csf1r cKO mice. Mechanistically, bone morphogenetic protein (BMP) signaling was found to contribute to ectopic calcification. Reanalysis of public single-cell sequencing data and lineage-tracing analysis using Cdh5 ^creERT2 mice revealed that endothelial-to-mesenchymal transition (EndoMT) is also a key contributor to ectopic calcification, as evidenced by the high expression of EndoMT-related markers in mesenchymal progenitor cells. Notably, the administration of BMP inhibitors reduced calcification and promoted muscle regeneration. Thus, F4/80(+)Csf1r(-) macrophages and BMP signals represent promising therapeutic targets for preventing ectopic calcifications triggered by trauma, burns, infections, or surgical interventions.