{"title":"Salivary Glands and Viral Pathogenesis.","authors":"N Atyeo, J O Maldonado, B M Warner, J A Chiorini","doi":"10.1177/00220345231222871","DOIUrl":"10.1177/00220345231222871","url":null,"abstract":"<p><p>The oral cavity is an epidemiologically relevant route of viral transmission due to the shedding of viruses in saliva. With advancements in salivary diagnostics, an increasing number of viruses have been detected. However, the anatomic source of virus in saliva is still largely unknown. Some viruses have a well-established tropism for the salivary glands (SGs), and recent studies have emphasized the importance of the glands as potential reservoirs for infectious viruses. Viral infections of the SGs have been linked to acute and chronic SG pathology and may be associated with SG dysfunction, with phenotypes similar to those seen in SjÖgren's disease (SjD), an autoimmune condition that affects the salivary and lacrimal glands. Understanding the breadth of viruses that infect the SG and the conserved or distinct host responses to these infections may provide insights into the pathogenesis of virus-mediated SG diseases. There is a need for further research to fully understand the molecular mechanisms by which viruses enter and replicate in the glands, their physiologic impact on SG function, and whether the SGs can serve as a long-term reservoir for infectious viral particles. The purpose of this review is to highlight a group of viruses that infect the salivary gland: hepatitis C virus, hepatitis D virus, severe acute respiratory syndrome coronavirus 2, enteric viruses, human T-cell leukemia virus type I, human immunodeficiency virus, human cytomegalovirus, and BK polyomavirus. We focus on the effects of viral infection on salivary gland (SG) inflammation, function, and its association with SjD.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"227-234"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A L Altrieth, J Kenney, D A Nelson, E G Suarez, V Gellatly, S Gabunia, M Larsen
{"title":"Single-Cell Transcriptomic Analysis of Salivary Gland Endothelial Cells.","authors":"A L Altrieth, J Kenney, D A Nelson, E G Suarez, V Gellatly, S Gabunia, M Larsen","doi":"10.1177/00220345231219987","DOIUrl":"10.1177/00220345231219987","url":null,"abstract":"<p><p>Vascular endothelial cells have important tissue-specific functions in fibrosis and regeneration. In the salivary gland, endothelial cells are required for proper development, but their roles within adult glands are largely unknown. To identify ligand-receptor interactions between endothelial cells and other cell types that may be important during fibrosis and regeneration, we used a reversible ductal ligation injury. To induce injury, a clip was applied to the primary ducts for 14 d, and to induce a regenerative response, the clip was subsequently removed for 5 d. To identify endothelial cell-produced factors, we used single-cell RNA sequencing of stromal-enriched cells from adult female submandibular and sublingual salivary glands. Transcriptional profiles of homeostatic salivary gland endothelial cells were compared to endothelial cells of other organs. Salivary gland endothelial cells expressed many unique genes and displayed the highest overlap in gene expression with other fenestrated endothelial cells from the colon, small intestine, and kidney. Comparison of the 14-d ligated, mock-ligated, and 5-d deligated stromal-enriched transcripts and lineage tracing revealed that endothelial cells retain their identity following ligation and recovery from injury. CellChat and NATMI were used to predict changes in ligand-receptor interactions from endothelial cells to other cells in response to ligation and deligation. CellChat and NATMI predicted that after ligation, interactions with fibroblasts, epithelial cells, and glial cells were increased, and following deligation, interactions with pericyte, glia, fibroblasts, and immune cells were increased. Some of the highest-ranked interactions predicted in ligated compared to mock endothelial cells were between glial cells via <i>Col4a2-Cd93</i> and <i>Jag2-Notch1</i>, as well as epithelial cells via <i>Pecam1-Cd38</i>, while in deligated compared to ligated endothelial cells, the top interactions were between fibroblasts via <i>Ntf3-Ntrk2</i>, glial cells via <i>Hspg2-Itgb1</i>, and pericytes via <i>Jam2-F11r</i>. Understanding salivary gland endothelial cell signaling will inform future endothelial cell-based regenerative therapies.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":"103 3","pages":"269-278"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N Zayed, H Munjaković, M K Aktan, K Simoens, K Bernaerts, N Boon, A Braem, F Pamuk, M Saghi, W Van Holm, A Fidler, R Gašperšič, W Teughels
{"title":"Electrolyzed Saline Targets Biofilm Periodontal Pathogens In Vitro.","authors":"N Zayed, H Munjaković, M K Aktan, K Simoens, K Bernaerts, N Boon, A Braem, F Pamuk, M Saghi, W Van Holm, A Fidler, R Gašperšič, W Teughels","doi":"10.1177/00220345231216660","DOIUrl":"10.1177/00220345231216660","url":null,"abstract":"<p><p>Preventing the development and recurrence of periodontal diseases often includes antimicrobial mouthrinses to control the growth of the periodontal pathogens. Most antimicrobials are nonselective, targeting the symbiotic oral species as well as the dysbiosis-inducing ones. This affects the overall microbial composition and metabolic activity and consequently the host-microbe interactions, which can be detrimental (associated with inflammation) or beneficial (health-associated). Consequently, guiding the antimicrobial effect for modulating the microbial composition to a health-associated one should be considered. For such an approach, this study investigated electrolyzed saline as a novel rinse. Electrolyzed saline was prepared from sterile saline using a portable electrolysis device. Multispecies oral homeostatic and dysbiotic biofilms were grown on hydroxyapatite discs and rinsed daily with electrolyzed saline (EOS). Corresponding positive (NaOCl) and negative (phosphate-buffered saline) controls were included. After 3 rinses, biofilms were analyzed with viability quantitative polymerase chain reaction and scanning electron microscopy. Supernatants of rinsed biofilms were used for metabolic activity analysis (high-performance liquid chromatography) through measuring organic acid content. In addition, human oral keratinocytes (HOKs) were exposed to EOS to test biocompatibility (cytotoxicity and inflammation induction) and also to rinsed biofilms to assess their immunogenicity after rinsing. Rinsing the dysbiotic biofilms with EOS could reduce the counts of the pathobionts (>3 log<sub>10</sub> Geq/mm<sup>2</sup> reduction) and avert biofilm dysbiosis (≤1% pathobiont abundance), leading to the dominance of commensal species (≥99%), which altered both biofilm metabolism and interleukin 8 (IL-8) induction in HOKs. EOS had no harmful effects on homeostatic biofilms. The scanning electron micrographs confirmed the same. In addition, tested concentrations of EOS did not have any cytotoxic effects and did not induce IL-8 production in HOKs. EOS showed promising results for diverting dysbiosis in in vitro rinsed biofilms and controlling key periopathogens, with no toxic effects on commensal species or human cells. This novel rinsing should be considered for clinical applications.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"243-252"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139379043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Pandi, S Angabo, H Makkawi, H Benyamini, S Elgavish, G Nussbaum
{"title":"<i>P. gingivalis</i>-Induced TLR2 Interactome Analysis Reveals Association with PARP9.","authors":"K Pandi, S Angabo, H Makkawi, H Benyamini, S Elgavish, G Nussbaum","doi":"10.1177/00220345231222181","DOIUrl":"10.1177/00220345231222181","url":null,"abstract":"<p><p><i>Porphyromonas gingivalis</i> is a Gram-negative anaerobic bacterium strongly associated with periodontal disease. Toll-like receptor 2 (TLR2) is indispensable for the host response to <i>P. gingivalis</i>, but <i>P. gingivalis</i> escapes from immune clearance via TLR2-dependent activation of phosphoinositide-3-kinase (PI3K). To probe the TLR2-dependent escape pathway of <i>P. gingivalis</i>, we analyzed the TLR2 interactome induced following <i>P. gingivalis</i> infection or activation by a synthetic lipopeptide TLR2/1 agonist on human macrophages overexpressing TLR2. Interacting proteins were stabilized by cross-linking and then immunoprecipitated and analyzed by mass spectrometry. In total, 792 proteins were recovered and network analysis enabled mapping of the TLR2 interactome at baseline and in response to infection. The <i>P. gingivalis</i> infection-induced TLR2 interactome included the poly (ADP-ribose) polymerase family member mono-ADP-ribosyltransferase protein 9 (PARP9) and additional members of the PARP9 complex (DTX3L and NMI). PARP9 and its complex members are highly upregulated in macrophages exposed to <i>P. gingivalis</i> or to the synthetic TLR2/1 ligand Pam<sub>3</sub>Cys-Ser-(Lys)<sub>4</sub> (PAM). Consistent with its known role in virally induced interferon production, PARP9 knockdown blocked type I interferon (IFN-I) production in response to <i>P. gingivalis</i> and reduced inflammatory cytokine production. We found that <i>P. gingivalis</i> drives signal transducer and activation of transcription (STAT) 1 (S727) phosphorylation through TLR2-PARP9, explaining PARP9's role in the induction of IFN-I downstream of TLR2. Furthermore, PARP9 knockdown reduced PI3K activation by <i>P. gingivalis</i>, leading to improved macrophage bactericidal activity. In summary, PARP9 is a novel TLR2 interacting partner that enables IFN-I induction and <i>P. gingivalis</i> immune escape in macrophages downstream of TLR2 sensing.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"329-338"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Deng, Q Li, K K H Svoboda, L A Opperman, L B Ruest, X Liu
{"title":"Gli1<sup>+</sup> Periodontal Mesenchymal Stem Cells in Periodontitis.","authors":"Y Deng, Q Li, K K H Svoboda, L A Opperman, L B Ruest, X Liu","doi":"10.1177/00220345231220915","DOIUrl":"10.1177/00220345231220915","url":null,"abstract":"<p><p>Periodontal mesenchymal stem cells (MSCs) play a crucial role in maintaining periodontium homeostasis and in tissue repair. However, little is known about how periodontal MSCs in vivo respond under periodontal disease conditions, posing a challenge for periodontium tissue regeneration. In this study, Gli1 was used as a periodontal MSC marker and combined with a Gli1-cre ERT2 mouse model for lineage tracing to investigate periodontal MSC fate in an induced periodontitis model. Our findings show significant changes in the number and contribution of Gli1<sup>+</sup> MSCs within the inflamed periodontium. The number of Gli1<sup>+</sup> MSCs that contributed to periodontal ligament homeostasis decreased in the periodontitis-induced teeth. While the proliferation of Gli1<sup>+</sup> MSCs had no significant difference between the periodontitis and the control groups, more Gli1<sup>+</sup> MSCs underwent apoptosis in diseased teeth. In addition, the number of Gli1<sup>+</sup> MSCs for osteogenic differentiation decreased during the progression of periodontitis. Following tooth extraction, the contribution of Gli1<sup>+</sup> MSCs to the tooth socket repair was significantly reduced in the periodontitis-induced teeth. Collectively, these findings indicate that the function of Gli1<sup>+</sup> MSCs in periodontitis was compromised, including reduced contribution to periodontium homeostasis and impaired injury response.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"279-288"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S L Fu, Y Y Qian, A N Dai, H Y Li, X H Jin, W T He, S Kang, P H Ding
{"title":"<i>Casp11</i> Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis.","authors":"S L Fu, Y Y Qian, A N Dai, H Y Li, X H Jin, W T He, S Kang, P H Ding","doi":"10.1177/00220345231221712","DOIUrl":"10.1177/00220345231221712","url":null,"abstract":"<p><p>Periodontitis (PD) is the primary cause of tooth loss in adults. <i>Porphyromonas gingivalis</i> (<i>P.g</i>), a keystone pathogen, has been identified as a crucial contributor to this process. Pyroptosis activation in PD is acknowledged, with accumulating evidence underscoring the crucial role of Caspase-11 (described as Caspase-4/5 in humans)-mediated noncanonical pyroptosis. However, the mechanism behind its impact on PD remains unclear. In this study, we delved into the interplay between the Caspase-11-mediated noncanonical pyroptosis, subgingival microbiota alteration, and macrophage polarization. Clinical samples from PD patients revealed heightened expression of Caspase-4, gasdermin-D, and their active fragments, pointing to the activation of the noncanonical pyroptosis. Single-cell sequencing analysis linked Caspase-4 with gingival macrophages, emphasizing their involvement in PD. In vitro cell experiments confirmed that <i>P.g</i>-induced pyroptosis was activated in macrophages, with <i>Casp11</i> deficiency attenuating these effects. In an experimental PD mouse model, <i>Casp11</i> deficiency led to an alteration in subgingival microbiota composition and reduced alveolar bone resorption. <i>Casp11</i><sup><i>-/-</i></sup> mice cohousing with wild-type mice confirmed the alteration of the subgingival microbiota and aggravated the alveolar bone resorption. Notably, <i>Casp11</i> deficiency led to decreased M1-polarized macrophages, corresponding with reduced alveolar bone resorption, uncovering a connection between subgingival microbiota alteration, macrophage M1 polarization, and alveolar bone resorption. Taken together, we showed that Caspase-11 fulfilled a crucial role in the noncanonical pyroptosis in PD, potentially influencing the subgingival microbiota and linking to M1 polarization, which was associated with alveolar bone resorption. These findings underscored the pivotal role of the Caspase-11-mediated noncanonical pyroptosis in PD pathogenesis and may provide critical insights into potential therapeutic avenues for mitigating PD.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"298-307"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V Chrepa, S Villasenor, A Mauney, G Kotsakis, L Macpherson
{"title":"Cannabidiol as an Alternative Analgesic for Acute Dental Pain.","authors":"V Chrepa, S Villasenor, A Mauney, G Kotsakis, L Macpherson","doi":"10.1177/00220345231200814","DOIUrl":"10.1177/00220345231200814","url":null,"abstract":"<p><p>Odontogenic pain can be debilitating, and nonopioid analgesic options are limited. This randomized placebo-controlled clinical trial aimed to assess the effectiveness and safety of cannabidiol (CBD) as an analgesic for patients with emergency acute dental pain. Sixty-one patients with moderate to severe toothache were randomized into 3 groups: CBD10 (CBD 10 mg/kg), CBD20 (CBD 20 mg/kg), and placebo. We administered a single dose of respective oral solution and monitored the subjects for 3 h. The primary outcome measure was the numerical pain differences using a visual analog scale (VAS) from baseline within and among the groups. Secondary outcome measures included ordinal pain intensity differences, the onset of significant pain relief, maximum pain relief, changes in bite force within and among the groups, psychoactive effects, mood changes, and other adverse events. Both CBD groups resulted in significant VAS pain reduction compared to their baseline and the placebo group, with a maximum median VAS pain reduction of 73% from baseline pain at the 180-min time point (<i>P</i> < 0.05). CBD20 experienced a faster onset of significant pain relief than CBD10 (15 versus 30 min after drug administration), and both groups reached maximum pain relief at 180-min. Number needed to treat was 3.1 for CBD10 and 2.4 for CBD20. Intragroup comparisons showed a significant increase in bite forces in both CBD groups (<i>P</i> < 0.05) but not in the placebo group (<i>P</i> > 0.05). CBD20 resulted in a significant difference in mean percent bite force change in the 90- and 180-min time points compared to the placebo group (<i>P</i> < 0.05). Compared to placebo, sedation, diarrhea, and abdominal pain were significantly associated with the CBD groups (<i>P</i> < 0.05). There were no other significant psychoactive or mood change effects. This randomized trial provides the first clinical evidence that oral CBD can be an effective and safe analgesic for dental pain.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"235-242"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cannabidiol for Toothache: Ups, Downs, and Regulatory Considerations.","authors":"K N Theken, E V Hersh","doi":"10.1177/00220345231223691","DOIUrl":"10.1177/00220345231223691","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"225-226"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E Buetas, M Jordán-López, A López-Roldán, A Mira, M Carda-Diéguez
{"title":"Impact of Periodontitis on the Leakage of Oral Bacteria to the Gut.","authors":"E Buetas, M Jordán-López, A López-Roldán, A Mira, M Carda-Diéguez","doi":"10.1177/00220345231221709","DOIUrl":"10.1177/00220345231221709","url":null,"abstract":"<p><p>Colorectal cancer (CRC) and periodontitis have recently been related due to the higher incidence of CRC in periodontal patients and the involvement of periodontal pathogens in carcinogenesis, suggesting that leakage from the oral cavity to the gut occurs. However, the magnitude of this pass-through in healthy individuals is controversial, and the effect that periodontitis could play in it is understudied. To evaluate the rate of bacterial leakage from the oral cavity to the gut, we analyzed the microbial composition of saliva, subgingival plaque, and fecal samples in healthy individuals without gastrointestinal disorders, including 20 periodontitis patients and 20 oral healthy controls, using PacBio full-length 16S rRNA gene sequencing. As expected, we observed a higher abundance of periodontal pathogens in the subgingival plaque and saliva of periodontal patients. In contrast, no significant differences were found between the fecal samples of both groups, implying that gut samples from periodontal patients were not enriched in periodontal pathogens. <i>Fusobacterium nucleatum</i>, a biomarker of CRC, was not found in the fecal samples of any participant. Our study does show a small leakage of some oral bacteria (mainly streptococci) to the gut, regardless of periodontal health status. Future studies should test whether other host factors and/or the preexistence of a gut disorder must be present in addition to periodontitis to promote the colonization of the gut by oral pathogens. The absence of periodontal pathogens in feces supports the idea that these bacteria could be used as biomarkers of intestinal disorders, including CRC.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"289-297"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Huang, R Ge, J Qian, J Lu, D Qiao, R Chen, H Jiang, D Cui, T Zhang, N Wang, S He, M Wang, F Yan
{"title":"Lacticaseibacillus rhamnosus GG Improves Periodontal Bone Repair via Gut-Blood Axis in Hyperlipidemia.","authors":"Y Huang, R Ge, J Qian, J Lu, D Qiao, R Chen, H Jiang, D Cui, T Zhang, N Wang, S He, M Wang, F Yan","doi":"10.1177/00220345231217402","DOIUrl":"10.1177/00220345231217402","url":null,"abstract":"<p><p>Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of <i>Lacticaseibacillus rhamnosus</i> GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed (<i>n</i> = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro-computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography-mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage (<i>P</i> < 0.05) but had little effect on oral flora. After LGG gavage, <i>Staphylococcus</i>, <i>Corynebacterium</i>, and <i>Collinsella</i> in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone (<i>P</i> < 0.05). These key genera were correlated with BV/TV and BV (<i>P</i> < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera (<i>P</i> < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut-blood-bone axis.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"253-262"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}