Efficacy of photodynamic therapy as an adjunct to scaling and root planing on clinical parameters and microbial composition in subgingival plaque of periodontitis patients: A split-mouth randomized clinical trial.

BACKGROUND: The aim of this study was to assess the efficacy of photodynamic therapy (PDT) as an adjunct to scaling and root planing (SRP) on clinical parameters and microbial composition in subgingival plaque of periodontitis patients. METHODS: Seventeen patients were included in this split-mouth randomized clinical trial. Sites with probing pocket depth (PPD) ≥5 mm in combination with bleeding on probing in different quadrants were randomized into the control group, the group with a single PDT application right after SRP, and the group with three repeated PDT applications 1 week after SRP. The subgingival plaque was collected for 16S rRNA gene sequencing at baseline, Week 2, and Week 8. RESULTS: Seventeen patients with 60 sites completed this 8-week follow-up, and 157 subgingival plaques were successfully analyzed by sequencing. Significant improvements were observed in two primary outcomes: PPD at Week 8 and subgingival microbial composition. Compared to the control group, the repeated-PDT group showed a notable improvement in PPD, substantial alterations in the microbial profile, including a reduction in α-diversity and anaerobic bacteria, and an increase in aerobic bacteria at Week 2. Secondary outcomes, such as clinical attachment level and sulcus bleeding index, also showed improvement at Week 8. Furthermore, both the single- and repeated-PDT groups exhibited a decrease in periodontopathogens and an increase in beneficial bacteria compared with baseline. CONCLUSION: PDT promotes changes in the microbial composition of periodontitis patients' subgingival plaque in a direction favorable to periodontal health, and repeated PDT is a promising adjunctive therapy for periodontal treatment.

CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

Metagenomic Sequencing Analysis Identifies Cross-Cohort Gut Microbial Signatures Associated With Age-Related Macular Degeneration.

Purpose: Alterations in the gut microbiota have been associated with age-related macular degeneration (AMD). However, the dysbiosis shared by different ethnicity and geographic groups, which may associate with the disease pathogenesis, remain underexplored. Here, we characterized dysbiosis of the gut microbiota in patients with AMD from Chinese and Swiss cohorts and identified cross-cohort signatures associated with AMD. Methods: Shotgun metagenomic sequencing was performed on fecal samples from 30 patients with AMD and 30 healthy subjects. Published datasets with 138 samples from Swiss patients with AMD and healthy subjects were re-analyzed. Comprehensive taxonomic profiling was conducted by matching to the RefSeq genome database, metagenome-assembled genome (MAG) database, and Gut Virome Database (GVD). Functional profiling was performed by reconstruction of the MetaCyc pathways. Results: The α-diversity of the gut microbiota was decreased in patients with AMD according to taxonomic profiles generated using MAG but not RefSeq database as reference. The Firmicutes/Bacteroidetes ratio was also decreased in patients with AMD. Among AMD-associated bacteria shared between Chinese and Swiss cohorts, Ruminococcus callidus, Lactobacillus gasseri, and Prevotellaceae (f) uSGB 2135 were enriched in patients with AMD, whereas Bacteroidaceae (f) uSGB 1825 was depleted in patients with AMD and was negatively associated with hemorrhage size. Bacteroidaceae was one of the major hosts of phages associated with AMD. Three degradation pathways were reduced in AMD. Conclusions: These results demonstrated that dysbiosis of the gut microbiota was associated with AMD. We identified cross-cohort gut microbial signatures involving bacteria, viruses, and metabolic pathways, which potentially serve as promising targets for the prevention or treatment of AMD.