Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.

The association between Porphyromonas gingivalis infection and oral squamous cell carcinoma (OSCC) has been established by numerous epidemiological studies. However, the underlying mechanism specific to this connection remains unclear. By bioinformatical analysis, we identified ZFP36 as a potentially significant co-expressed gene in both the OSCC gene database and the persistent infection model of P. gingivalis. To further investigate the role of ZFP36, we established a cell model that human immortalized oral epithelial cells (HIOECs) that were sustainedly infected by P. gingivalis (MOI = 1) for a duration of 30 weeks. Our findings indicated that sustained infection with P. gingivalis inhibited the expression of ZFP36 protein and induced changes in the biological behaviour of HIOECs. The mechanism investigation demonstrated the potential role of ZFP36 in regulating the cancer-related biological behaviour of HIOECs. Subsequent studies revealed that highly expressed CCAT1 could serve as a molecular scaffold in the formation of the ZFP36/CCAT1/MK2 complex. This complex formation enhanced the binding abundance of MK2 and ZFP36, thereby promoting the inhibition of ZFP36 protein phosphorylation. To summarize, low expression of ZFP36 protein under persistent P. gingivalis infection enhances the cancer-related biological behaviour of HIOECs.

Periodontitis, which is related to various systemic diseases, is a chronic inflammatory disease caused by periodontal dysbiosis of the microbiota. Multiple factors can influence the interaction of periodontitis and associated inflammatory disorders, among which host immunity is an important contributor to this interaction. Innate immunity can be activated aberrantly because of the systemic inflammation induced by periodontitis. This aberrant activation not only exacerbates periodontal tissue damage but also impairs systemic health, triggering or aggravating inflammatory comorbidities. Therefore, innate immunity is a potential therapeutic target for periodontitis and associated inflammatory comorbidities. This review delineates analogous aberrations of innate immune cells in periodontitis and comorbid conditions such as atherosclerosis, diabetes, obesity, and rheumatoid arthritis. The mechanisms behind these changes in innate immune cells are discussed, including trained immunity and clonal hematopoiesis of indeterminate potential (CHIP), which can mediate the abnormal activation and myeloid-biased differentiation of hematopoietic stem and progenitor cells. Besides, the expansion of myeloid-derived suppressor cells (MDSCs), which have immunosuppressive and osteolytic effects on peripheral tissues, also contributes to the interaction between periodontitis and its inflammatory comorbidities. The potential treatment targets for relieving the risk of both periodontitis and systemic conditions are also elucidated, such as the modulation of innate immunity cells and mediators, the regulation of trained immunity and CHIP, as well as the inhibition of MDSCs' expansion.

BackgroundEpidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear. Methods and ResultsA COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90 alpha/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90 alpha and MLKL in serum and lung tissue verified that Hsp90 alpha/MLKL was up-regulated. ConclusionThese results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90 alpha/MLKL might participate in.

Prevention of atherosclerotic cardiovascular disease (ASCVD) is important in individuals with metabolic syndrome components (MetS), and periodontitis may play an important role in this process. This study aims to evaluate the association between periodontitis and ASCVD in participants with the components of MetS, including obesity, dysglycemia, hypertension, and dyslipidemia. This study conducted followed the MOOSE reporting guidelines and the PRISMA 2020 guidelines. EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed and OpenGrey were searched for observational studies about the linkage of periodontitis to ASCVD in people with MetS components up to April 9, 2023. Cohort, case-control and cross-sectional studies were included after study selection. Quality evaluation was carried out using the original and modified Newcastle-Ottawa Scale as appropriate. Random-effects model was employed for meta-analysis. Nineteen studies were finally included in the quality analysis, and all of them were assessed as moderate to high quality. Meta-analyses among fifteen studies revealed that the participants with periodontitis were more likely to develop ASCVD in those who have dysglycemia (RR = 1.25, 95

AIM:To assess the relationship between dietary antioxidant intake and periodontal health in US adults and the potential role of mitochondrial function. MATERIALS AND METHODS:We performed a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Dietary antioxidant intake was evaluated using three diet-related indices: dietary oxidative balance score (DOBS), dietary total antioxidant capacity (DTAC) of antioxidant vitamins and composite dietary antioxidant index (CDAI). Periodontal parameters included attachment loss (AL) and probing pocket depth (PPD). Mitochondrial dysfunction was assessed using the methylmalonic acid (MMA) level. Weighted multivariable linear regression analyses were employed to investigate the association between dietary antioxidant intake and periodontal status. Additionally, exploratory mediation analyses were conducted to determine the mediating effect of MMA on the association. RESULTS:Totally, 5520 participants were included in our study. Participants with higher DOBS and DTAC scores had lower mean AL/PPD and MMA values. CDAI was negatively associated with mean AL and PPD. Furthermore, MMA mediated 9.4% and 4.9% of the associations between DOBS and mean AL and mean PPD, respectively. MMA also accounted for 7.2% and 3.3% of the association between DTAC and mean AL and PPD, respectively. CONCLUSIONS:The findings support that dietary antioxidant intake helps in improving periodontal health, possibly and partially by enhancing mitochondrial function.

Dental biofilm is a highly complicated and dynamic structure comprising not only microbial communities but also the surrounding matrix of extracellular polymeric substances (EPS), including polysaccharides, proteins, extracellular DNA (eDNA) and other biopolymers. In recent years, the important role of bacterial eDNA in dental biofilms has gradually attracted attention. In this review, we present recent studies on the presence, dynamic conformation and release of oral bacterial eDNA. Moreover, updated information on functions associated with oral bacterial eDNA in biofilm formation, antibiotic resistance, activation of the immune system and immune evasion is highlighted. Finally, we summarize the role of oral bacterial eDNA as a promising target for the treatment of oral diseases. Increasing insight into the versatile roles of bacterial eDNA in dental biofilms will facilitate the prevention and treatment of biofilm-induced oral infections.

ObjectivesThis study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms. Materials and methodsThe expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyzed using bioinformatics analysis and validated in vivo. An in vitro model was constructed to evaluate ferroptosis by mitochondria morphology, content of iron and GSH, and level of lipid peroxidation, FTL, GPX4 and SLC7A11. The iron concentration was changed with iron chelator DFO and iron supplementation FAC. The epithelial impairment was assessed by protein expression. To investigate the mechanism, si-MYB (a negative transcription factor of SLC7A11) and GPX4 inhibitor RSL3 were employed. ResultsCDH1, OCLN, ZO-1 and GPX4 expression was decreased, while FTL expression was elevated in periodontitis tissues. Infected cells showed ferroptosis change of the mitochondria with higher level of lipid peroxidation, iron, FTL and lower level of GPX4, GSH, SLC7A11. FAC augmented ferroptosis and weakened epithelial junction, while DFO exhibited a counteractive effect. Silencing MYB rescued SLC7A11, GPX4 and epithelial junction proteins, which was hindered by RSL3. ConclusionsOur study demonstrated that P. gingivalis weakened the oral epithelial barrier by causing ferroptosis via inhibiting SLC7A11/GSH/GPX4 axis.

AIM:Blood-brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process. MATERIALS AND METHODS:C57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav-1 levels were measured. The mechanisms of Ddx3x-induced regulation on Mfsd2a by arginine-specific gingipain A (RgpA) in BMECs were explored. RESULTS:P. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up-regulated Cav-1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav-1 regulatory axis was activated. CONCLUSIONS:Gingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav-1 axis.

BACKGROUND To examine the relationship between the systemic immune-inflammation index (SII) and periodontitis and to investigate possible effect modifiers. METHODS Data used in the present cross-sectional study are from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 (N = 10,301). The SII was calculated using the following formula: (neutrophils count × platelet count)/lymphocytes count. The category of periodontitis was defined by the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification. We employed natural cubic spline and multivariable logistic regression analyses to evaluate the associations of the SII with periodontitis. RESULTS The associations between SII and periodontal health followed a J-shape (p < 0.001). The risk of periodontitis tended to reduce with the increment of log2 (SII) in participants with log2 (SII) ≤ 8.66 (odds radio [OR] = 0.83; 95% CI: 0.69-0.999), especially among non-Hispanic Whites (OR = 0.70; 95% CI: 0.52-0.95), and increased with the increment of log2 (SII) in participants with log2 (SII) > 8.66 (OR = 1.19; 95% CI: 1.02-1.38). A similar trend was also observed between the SII and the number of sites with probing pocket depth (PPD) ≥4 mm and clinical attachment loss (CAL) ≥ 3 or 5 mm. Furthermore, we found a significantly stronger correlation between lymphocytes and either neutrophils or platelets in individuals with log2 (SII) > 8.66, as opposed to those with log2 (SII) ≤ 8.66. CONCLUSIONS There is a J-shaped association between SII and periodontitis in US adults, with an inflection point of log2 (SII) at 8.66, which may provide potential adjunctive treatment strategies for periodontitis with different immune response states. Further prospective trials are still required to confirm our findings.

本文对以牙周致病菌为主的口腔细菌在口腔鳞状细胞癌(OSCC)发生、发展中的作用和相关调控机制,以及口腔细菌在OSCC的预防、诊断、治疗和预后的临床应用进行综述.

Background Oral squamous cell carcinoma (OSCC), the most common type of primary malignant tumor in the oral cavity, is a lethal disease with high recurrence and mortality rates. Butyrate, a metabolite produced by periodontal pathogens, has been linked to oral diseases. The purpose of this study was to evaluate the effect of sodium butyrate (NaB) on the proliferation, migration, and invasion of OSCC cells in vitro and to explore the potential mechanism. Methods Two OSCC cell lines (HSC-4 and SCC-9) were treated with NaB at different concentrations. The cell proliferation was assayed by CCK-8, ethylene deoxyuridine (EdU), and flow cytometry. Wound healing and transwell assay were performed to detect cell migration and invasion. Changes in epithelial-mesenchymal transition (EMT) markers, including E-cadherin, Vimentin, and SNAI1, were evaluated by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescent staining. The expression levels of matrix metalloproteinases (MMPs) were analyzed by qRT-PCR and gelatin zymography. Results Our results showed that NaB inhibited the proliferation of OSCC cells and induced cell cycle arrest at G1 phase, but NaB significantly enhanced cell migration and invasion compared with the control group. Further mechanistic investigation demonstrated that NaB induced EMT by increasing the expression of Vimentin and SNAI1, decreasing the expression of membrane-bound E-cadherin, and correspondingly promoting E-cadherin translocation from the membrane to the cytoplasm. In addition, the overexpression of MMP1/2/9/13 was closely related to NaB treatment. Conclusions Our study conclude that butyrate may promote the migration and invasion of OSCC cells by inducing EMT. These findings indicate that butyrate may contribute to OSCC metastasis.

Necroptosis, a new type of regulated cell death with massive release of damage-associated molecular patterns (DAMPs), is involved in the pathogenesis of periodontitis. However, the role of necroptosis in oral epithelial cells and the following effect on macrophages activation remain unknown. Human immortalized oral epithelial cells were stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Cell death was assessed while expressions of RIPK3/MLKL and toll-like receptors (TLRs) were evaluated. Necrosulfonamide (NSA), an inhibitor of MLKL was applied to block necroptosis. The expression of DAMPs and the epithelial connection protein were evaluated by qPCR and immunofluorescence, respectively. Immortalized human monocytes U937 were induced into the M0 or M2 subset, and influences of HIOECs-derived DAMPs on macrophage polarization as well as activation of the Mincle/SYK axis were assessed. P. gingivalis LPS could be recognized by TLR2 and regulates necroptosis of HIOECs by activating RIPK3/MLKL. NSA inhibited cell death of HIOECs, alleviated impaired epithelial connection, and inhibited expressions of DAMPs. Low dose of DAMPs derived from HIOECs promoted M2-like polarization by activating the Mincle/SYK axis, which was significantly suppressed with increased doses of DAMPs. P. gingivalis LPS destructed oral epithelial cells via RIPK3/MLKL-mediated necroptosis, which further regulated macrophage activation via DAMPs from oral epithelial cells.

Accumulating evidence links Fusobacterium nucleatum with tumorigenesis. Our previous study demonstrated that F. nucleatum infection can induce epithelial‐mesenchymal transition (EMT) in oral epithelial cells and elaborated a probable signal pathway involved in the induction of EMT. However, the comprehensive profiling and pathways of other candidate genes involved in F. nucleatum promoting malignant transformation remain largely elusive. Here, we analysed the transcriptome profile of HIOECs exposed to F. nucleatum infection. Totally, 3307 mRNAs (ǀLog2FCǀ >1.5) and 522 lncRNAs (ǀLog2FCǀ >1) were identified to be differentially expressed in F. nucleatum ‐infected HIOECs compared with non‐infected HIOECs. GO and KEGG pathway analyses were performed to investigate the potential functions of the dysregulated genes. Tumour‐associated genes were integrated, and top 10 hub genes (FYN, RAF1, ATM, FOS, CREB, NCOA3, VEGFA, JAK2, CREM and ATF3) were identified by protein‐protein interaction (PPI) network, and Oncomine was used to validate hub genes' expression. LncRNA‐hub genes co‐expression network comprising 67 dysregulated lncRNAs were generated. Together, our study revealed the alteration of lncRNA and potential hub genes in oral epithelial cells in response to F. nucleatum infection, which may provide new insights into the shift of normal to malignant transformation initiated by oral bacterial infection.

Objectives This paper aims to study the effect of the active form of vitamin D (calcitriol) on the internalized Porphyromonas gingivalis in macrophages and to assess the role of autophagy during this process. Materials and methods Quantitative RT-PCR and bacteria culture were used to quantify live P. gingivalis internalized into U937-derived macrophages. Western blot assays were performed to detect the effect of P. gingivalis and calcitriol on autophagy in macrophages. Transmission electron microscope was used to observe the effect of calcitriol on the status of internalized P. gingivalis. Colocalization of P. gingivalis with the autophagosome and lysosome markers was observed by confocal laser scanning microscopy. Results Calcitriol caused a dose-dependent decrease in live P. gingivalis numbers and promoted both the endogenous and P. gingivalis-induced autophagy in macrophages. Calcitriol significantly promoted the destruction of P. gingivalis and the colocalization of P. gingivalis with autophagosome and lysosome markers. Conversely, with 3-MA, live P. gingivalis numbers in macrophages increased significantly and inhibition effect of calcitriol on the number of live P. gingivalis was attenuated. Conclusion In U937-derived macrophages, calcitriol may promote colocalization of P. gingivalis with autophagosomes and lysosomes, namely autophagy process, to degrade live P. gingivalis.

Fusobacterium nucleatum, an anaerobic oral opportunistic pathogen associated with periodontitis, has been considered to be associated with the development of oral squamous cell carcinoma (OSCC). However, the initial host molecular alterations induced by F. nucleatum infection which may promote predisposition to malignant transformation through epithelial–mesenchymal transition (EMT) have not yet been clarified. In the present study, we monitored the ability of F. nucleatum to induce EMT‐associated features, and our results showed that F. nucleatum infection promoted cell migration in either noncancerous human immortalized oral epithelial cells (HIOECs) or the two OSCC cell lines SCC‐9 and HSC‐4, but did not accelerate cell proliferation or cell cycle progression. Mesenchymal markers, including N‐cadherin, Vimentin, and SNAI1, were upregulated, while E‐cadherin was decreased and was observed to translocate to the cytoplasm. Furthermore, FadA adhesin and heat‐inactivated F. nucleatum were found to cause a similar effect as the viable bacterial cells. The upregulated lncRNA MIR4435‐2HG identified by the high‐throughput sequencing was demonstrated to negatively regulate the expression of miR‐296‐5p, which was downregulated in F. nucleatum‐infected HIOECs and SCC‐9 cells. The binding of MIR4435‐2HG and miR‐296‐5p was validated via a dual‐luciferase reporter assay. Additionally, knockdown of MIR4435‐2HG with siRNA leads to a decrease in SNAI1 expression, while miR‐296‐5p could further negatively and indirectly regulate SNAI1 expression via Akt2. Therefore, our study demonstrated that F. nucleatum infection could trigger EMT via lncRNA MIR4435‐2HG/miR‐296‐5p/Akt2/SNAI1 signaling pathway, and EMT process may be a probable link between F. nucleatum infection and initiation of oral epithelial carcinomas.

Porphyromonas gingivalis (P. gingivalis), one of the most important pathogens of periodontitis, is closely associated with the aggravation and recurrence of periodontitis and systemic diseases. Antibacterial peptide LL-37, transcribed from the cathelicidin antimicrobial peptide (CAMP) gene, exhibits a broad spectrum of antibacterial activity and regulates the immune system. In this study, we demonstrated that LL-37 reduced the number of live P. gingivalis (ATCC 33277) in HaCaT cells in a dose-dependent manner via an antibiotic-protection assay. LL-37 promoted autophagy of HaCaT cells internalized with P. gingivalis. Inhibition of autophagy with 3-methyladenine (3-MA) weakened the inhibitory effect of LL-37 on the number of intracellular P. gingivalis. A cluster of orthologous groups (COGs) and a gene ontology (GO) functional analysis were used to individually assign 65 (10%) differentially expressed genes (DEGs) to an “Intracellular trafficking, secretion, and vesicular transport” cluster and 306 (47.08%) DEGs to metabolic processes including autophagy. Autophagy-related genes, a tripartite motif-containing 22 (TRIM22), and lysosomal-associated membrane protein 3 (LAMP3) were identified as potentially involved in LL-37-induced autophagy. Finally, bioinformatics software was utilized to construct and predict the protein–protein interaction (PPI) network of CAMP-TRIM22/LAMP3-Autophagy. The findings indicated that LL-37 can reduce the quantity of live P. gingivalis internalized in HaCaT cells by promoting autophagy in these cells. The transcriptome sequencing and analysis also revealed the potential molecular pathway of LL-37-induced autophagy.

Bacterial infection influences genomic stability and integrity by causing DNA damage, which increases the possibility of tumor initiation and development. We aimed to investigate whether Fusobacterium nucleatum, one of the periodontal pathogens, promoted oral squamous cell carcinoma (OSCC) by causing DNA double-strand break (DSB). Tca8113 tongue squamous cell carcinoma cells were infected with F. nucleatum. The expression of γH2AX was detected by western blots and immunofluorescence. The proliferation and cell cycle alterations were tested by CCK8 and flow cytometry, respectively. The expression levels of Ku70, p53, and p27 were evaluated by quantitative real-time polymerase chain reaction and western blots. A plasmid was used for the overexpression of Ku70 to verify the possible relationship between Ku70 and p53. We confirmed the presence of DSBs in the response to F. nucleatum by detecting the expression of γH2AX. The cell proliferation ability was increased with an accelerated cell cycle while the expression of p27 was decreased. Meanwhile, the expression of Ku70 and wild p53 was downregulated. When Ku70 was overexpressed, the expression of wild p53 in response to F. nucleatum infection was upregulated and cell proliferation was accordingly inhibited. We concluded that F. nucleatum infection promoted the proliferation ability of Tca8113 by causing DNA damage via the Ku70/p53 pathway.

Recent investigations revealed the relationship between chronic periodontitis, Porphyromonas gingivalis and cancer. However, host genes that change in response to chronic infection with P. gingivalis and may contribute to oral cancer have remained largely unknown. In the present study, we aimed to comprehensively analyze microarray data obtained from the chronic infection model of immortalized oral epithelial cells that were persistently exposed to P. gingivalis for 15 weeks. Using protein-protein interaction (PPI) networks and Ingenuity Pathway Analysis (IPA), we identified hub genes, major biological processes, upstream regulators and genes potentially involved in tumor initiation and progression. We also validated gene expression and demonstrated genetic alteration of hub genes from clinical samples of head and neck cancer. Overall, we utilized bioinformatical methods to identify IL6, STAT1, LYN, BDNF, C3, CD274, PDCD1LG2, and CXCL10 as potential candidate genes that might facilitate the prevention and treatment of oral squamous cell carcinoma (OSCC), the most common type of head and neck squamous cell carcinoma (HNSCC).

Background The present study aimed to explore the effects of the active form of vitamin D (calcitriol, 1 alpha,25-dihydroxyvitamin D-3, 1 alpha,25 (OH)(2)D-3, 1,25D) on live Porphyromonas gingivalis internalized into KB cells and U937 cells. Methods Quantitative real-time polymerase chain reaction method was used to evaluate the number of surviving P. gingivalis internalized into KB cells and U937 cells. Transmission electron microscopy was used to detect P. gingivalis in cells. A western blot analysis was performed to observe LC3 expressions. Results 1) Treatment with 1,25D decreased the number of live P. gingivalis in KB cells and U937 cells in a dose-dependent manner. 2) Dividing P. gingivalis were found only in KB cells but not in U937 cells. The cell walls of most P. gingivalis in KB cells were intact, while those in U937 cells were disrupted. Treatment with 1,25D promoted the encapsulation of P. gingivalis in autophagosomes in both KB and U937 cells. 3) Both 1,25D treatment and P. gingivalis infection increased the LC3 II/I ratio. Furthermore, 1,25D treatment increased the P. gingivalis-upregulated LC3 II/I ratio. 4) Treatment with 3-methyladenine (3-MA) decreased the number of P. gingivalis by 11.41% in KB cells, while increased that by 121.51% in U937 cells. Under 1,25D treatment conditions, 3-MA treatment increased the number of P. gingivalis by 88.71% in KB cells and by 284.70% in U937 cells. Conclusions Autophagy may facilitate P. gingivalis survival in KB cells and eliminate P. gingivalis in U937 cells. Treatment with 1,25D may help decrease the number of live P. gingivalis in KB cells and U937 cells by promoting functional autophagy.