Interplay between periodontitis and chronic kidney disease
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Periodontitis impacts on thrombotic diseases: from clinical aspect to future therapeutic approaches
Periodontitis is a chronic inflammatory disease initiated by biofilm microorganisms and mediated by host immune imbalance. Uncontrolled periodontal infections are the leading cause of tooth loss in adults. Thrombotic diseases can lead to partial or complete obstruction of blood flow in the circulatory system, manifesting as organ or tissue ischemia and necrosis in patients with arterial thrombosis, and local edema, pain and circulatory instability in patients with venous thrombosis, which may lead to mortality or fatality in severe case. Recent studies found that periodontitis might enhance thrombosis through bacterial transmission or systemic inflammation by affecting platelet-immune cell interactions, as well as the coagulation, and periodontal therapy could have a prophylactic effect on patients with thrombotic diseases. In this review, we summarized clinical findings on the association between periodontitis and thrombotic diseases and discussed several novel prothrombotic periodontitis-related agents, and presented a perspective to emphasize the necessity of oral health management for people at high risk of thrombosis.
The blood pressure lowering effect of beetroot juice is impaired in periodontitis and recovered after periodontal treatment
We have previously demonstrated that subgingival levels of nitrate-reducing bacteria, as well as the in vitro salivary nitrate reduction capacity (NRC), were diminished in periodontitis patients, increasing after periodontal treatment. However, it remains unclear if an impaired NRC in periodontitis can affect systemic health. To determine this, the effect of nitrate-rich beetroot juice (BRJ) on blood pressure was determined in 15 periodontitis patients before and 70 days after periodontal treatment (i.e., professional mechanical plaque removal, oral hygiene instruction, and subgingival instrumentation), as well as in a healthy control group of 15 individuals. Additionally, subgingival and tongue samples were taken to analyse the bacterial composition with Illumina sequencing of the 16S rRNA gene. In healthy individuals, the systolic and diastolic blood pressure (SBP and DPB) decreased significantly (both P < 0.01) 90 min after BRJ intake, but not in periodontitis patients. However, after periodontal treatment, this blood pressure-lowering effect was recovered (P < 0.05 for SBP; P < 0.01 for DBP). Lower levels of salivary nitrate after identical doses of BRJ intake indicated a potentially higher NRC in healthy individuals (P < 0.05). Periodontitis-associated bacteria decreased in tongue and subgingival samples after periodontal treatment (P < 0.01). In contrast, nitrate-reducing bacteria were associated with health in both habitats, but increased only in subgingival plaque after periodontal treatment (P < 0.001). This is the first study showing that periodontitis could limit the blood-pressure lowering effects of nitrate reduction by the oral microbiota. We propose that an impaired NRC represents a potential link between periodontitis and systemic conditions, which should be confirmed in future randomized controlled trials. Future work should also aim to determine if nitrate prebiotic supplementation and/or tongue cleaning could improve the treatment of periodontitis and its associated comorbidities.
A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis
Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins – drivers or suppressors – associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.
Regulation of tryptophan-indole metabolic pathway in Porphyromonas gingivalis virulence and microbiota dysbiosis in periodontitis
Pathogenesis of periodontitis is marked by microbiota dysbiosis and disrupted host responses. Porphyromonas gingivalis is a keystone pathogen of periodontitis which expresses various crucial virulence factors. This study aimed to clarify the role and mechanisms of P. gingivalis tryptophan-indole metabolic pathway in the pathogenesis of periodontitis. This study showed that periodontitis patients exhibited elevated tryptophan metabolism and salivary pathogen abundance. Tryptophanase gene-deficiency altered proteome and metabolome of P. gingivalis, inhibited P. gingivalis virulent factors expression, biofilm growth, hemin utilization, cell adhesion/invasion and pro-inflammation ability. Tryptophan-indole pathway of P. gingivalis stimulated periodontitis biofilm formation and induced oral microbiota dysbiosis. In periodontitis mice, this pathway of P. gingivalis aggravated alveolar bone loss and gingival tissue destruction, causing oral and gut microbiota dysbiosis. This study indicates that the tryptophan-indole pathway serves as a significant regulator of P. gingivalis virulence and oral microbiota dysbiosis, which is also associated with gut dysbiosis.
A first-in-human study of quantitative ultrasound to assess transplant kidney fibrosis
Kidney transplantation is the optimal treatment for renal failure. In the United States, a biopsy at the time of organ procurement is often used to assess kidney quality to decide whether it should be used for transplant. This assessment is focused on renal fibrotic burden, because fibrosis is an important measure of irreversible kidney injury. Unfortunately, biopsy at the time of transplant is plagued by problems, including bleeding risk, inaccuracies introduced by sampling bias and rapid sample preparation, and the need for round-the-clock pathology expertise. We developed a quantitative algorithm, called renal H-scan, that can be added to standard ultrasound workflows to quickly and noninvasively measure renal fibrotic burden in preclinical animal models and human transplant kidneys. Furthermore, we provide evidence that biopsy-based fibrosis estimates, because of their highly localized nature, are inaccurate measures of whole-kidney fibrotic burden and do not associate with kidney function post-transplant. In contrast, we show that whole-kidney H-scan fibrosis estimates associate closely with post-transplant renal function. Taken together, our data suggest that the addition of H-scan to standard ultrasound workflows could provide a safe, rapid and easy-to-perform method for accurate quantification of transplant kidney fibrotic burden, and thus better prediction of post-transplant renal outcomes.
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