Porphyromonas gingivalis is a key periodontal pathogen in the relationship between periodontal and gastroenterological diseases

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that can eventually lead to liver cirrhosis and hepatocellular carcinoma. Porphyromonas gingivalis (P.g) is the main pathogen that causes periodontal disease, which participates in the development of NAFLD. The purpose of our study was to further study the direct role of P.g in NAFLD and the underlying molecular mechanism. An animal model of oral P.g administration was established, and liver function and pathology in this model were evaluated. The gut microbiome and metabolic products were analysed. Furthermore, the Th17/Treg balance in the spleen and liver was assessed. In our study, NAFLD was observed in all the mice that were orally administered P.g. The gut microbiome and metabolic products were altered after oral P.g administration. P.g and ferroptosis were observed in the livers of the mice after oral P.g administration. Additionally, ferroptosis was observed in hepatocytes in vitro, but it was reversed by ferroptosis inhibitors. In addition, P.g triggered an imbalance in the Th17/Treg ratio in the liver and spleen in vivo. These findings suggest that oral P.g administration directly induced NAFLD in mice, which may be dependent on the ferroptosis of liver cells that occurs through the Th17/Treg imbalance induced by disordered microbial metabolism. Therefore, improving the periodontal environment is a novel treatment strategy for preventing NAFLD.

Among dental pathologies, periodontal diseases occupy the 2nd place in prevalence after caries. The prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population in the world reaches 33.0% and is detected in all age categories. The presence of common risk factors suggests an indirect interaction between periodontitis and NAFLD, but the question of the possibility of direct interaction without the participation of “intermediaries” is relevant. The review examines the bidirectional relationship between periodontal pathology and NAFLD. The results of experimental and clinical studies indicate that periodontal bacteria, especially Porphyromonas gingivalis, correlate with the development of NAFLD. P. gingivalis has been detected in the liver, and LPS from this bacterium has been shown to be involved in the progression of NAFLD, suggesting a possible direct role of P. gingivalis in NAFLD. In addition, P. gingivalis causes disruption of the intestinal microbiocenosis, which contributes to the progression of NAFLD. There are two possible routes connecting the oral cavity and the liver - hematogenous and enteral diffusion of hepatotoxic components. The emerging concept of changes in the oral microbiota associated with periodontitis is closely related to the role of the mouth-gut-liver axis in the pathogenesis of NAFLD, based on the close relationship between the gut and liver connected by the enterohepatic circulation.

Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end‐stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by‐products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta‐analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease–related nonalcoholic fatty liver disease or periodontal disease–related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life‐threatening liver disease.

The association between periodontal disease and systemic disease has become a research hotspot. Porphyromonas gingivalis (P. gingivalis), a crucial periodontal pathogen, affects the development of systemic diseases. The pathogenicity of P. gingivalis is largely linked to interference with the host’s immunity. This review aims to discover the role of P. gingivalis in the modulation of the host’s adaptive immune system through a large number of virulence factors and the manipulation of cellular immunological responses (mainly mediated by T cells). These factors may affect the cause of large numbers of systemic diseases, such as atherosclerosis, hypertension, adverse pregnancy outcomes, inflammatory bowel disease, diabetes mellitus, non-alcoholic fatty liver disease, rheumatoid arthritis, and Alzheimer’s disease. The point of view of adaptive immunity may provide a new idea for treating periodontitis and related systemic diseases.

Is there a Relationship? A Contemporary ReviewT he Non-alcoholic fatty liver disease (NAFLD) it's a term used for several conditions caused by fat accumulation in the liver.One-fourth of the world's population is faced with this clinical situation.It is mostly seen in South America and the Middle East, and least in Africa. [1]Nevertheless, when considering its prevalence within the community, this malady emerges as one of the most frequently encountered liver diseases, demonstrating a notable association with elevated rates of liver-related mortality and morbidity. [2]By definition, NAFLD is a clinical picture in which insulin resistance, histopathological more than 5% steatosis of hepatocytes, or dense fat fractions by radiographic techniques are detected.This clinical situation is examined under two main headings non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (steatosis coexists with liver-cell injury and inflammation). [3,4] AFLD has 4 stages for developing; simple fatty liver (steatosis), non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis, and may liver cancer. [5]In advanced phases, this may result in liver transplantation.The patients with NAFLD show similar histological damage to alcoholic liver disease. [6]Oxidative and inflammatory responses play crucial roles in the shared pathogenesis of both NAFLD and nonalcoholic NASH. [7]ifestyle is an important point for developing this disease.Periodontal disease is a common inflammatory disease and is known to be related to other systemic diseases.This bidirectional relation between periodontal disease and other disease processes has led to outstanding research recently.In addition, periodontal disease has been advocated to exacerbate metabolic disorders including non-alcoholic fatty liver disease (NAFLD).In this traditional review, general characteristics of periodontal diseases, general characteristics of NAFLD/ Nonalcoholic steatohepatitis (NASH), and their causality were discussed for treatment providers.The collected data significantly corroborate a greater incidence of periodontal disease among individuals with NAFLD in comparison to the general healthy population.Healthcare professionals need to be aware of the association between NAFLD and periodontal disease thus patient management effectiveness can be enhanced.

WITHDRAWN: Evidence Synthesis to Advance Clinical Practice and Scientific Research: A CGH Pillar

To the Editor: Because epidemiological evidence supports an association between cardiovascular and periodontal disease, we assessed whether periodontal pathogens were present in atherosclerotic lesions. To detect invasive bacteria, the natural tropism of the bacteria toward human tissues was exploited. Further, bacterial presence was demonstrated using quantitative polymerase chain reaction (Q-PCR). This confirms the presence of periodontal pathogens in atherosclerotic lesions, whereby the bacteria could contribute to the vascular pathology either directly through their cytotoxicity or indirectly by inducing or exacerbating inflammation. Cardiovascular disease (CVD) is the leading cause of death in the in the United States.1 According to the American Heart Association’s statistics from 2003, there were no previous symptoms in 50% of men and 63% of women who died suddenly from CHD. In a 10-year follow-up study, ≈25% of coronary deaths in males and 15% in females occurred in persons in the lowest two quintiles of the multivariate Framingham Heart Study risk scores.2 This and other data have led to an emerging paradigm shift from coronary heart disease having a purely hereditary/nutritional causation to possibly having an infectious component.3 Many epidemiological studies strongly suggest that periodontitis may be a risk factor for coronary heart disease (CHD).4 Serologically, edentulousness and serum IgG-antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in 1163 men were recently shown to be associated with CHD.5 In a larger prospective study of 6950 subjects, the same authors provide serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.6 Previous studies have identified 16S rRNA of oral microbial pathogens, including P gingivalis and A actinomycetemcomitans , …

At the beginning of the 21st century, the concept of "periodontal medicine" was formed, considering the relationship between periodontal pathology and systemic diseases of the body. Currently, more than 50 systemic inflammatory diseases and concomitant diseases are associated with periodontal pathology. We searched the Pubmed and Scopus information databases for sources published before November 1, 2024, which considered the relationship between periodontal pathology and gastrointestinal cancer. In the current review, we focused on the epidemiological aspects of the relationship between periodontal diseases and gastrointestinal cancer, as well as possible mechanisms for the identified relationship between periodontal diseases and gastrointestinal cancer. Most of the sources found relate to the last decade, which indicates the relevance of analyzing the relationship between periodontal diseases and cancer. Epidemiological studies suggest a positive relationship with the overall risk of cancer and specific types of gastrointestinal cancer. Possible mechanisms of the relationship between periodontal diseases and cancer suggest the translocation of periodontal bacteria, primarily potential carcinogens Porphyromonas gingivalis and Fusobacterium nucleatum, by the hematogenous route or along the "mouth–intestinal"/"mouth–gastrointestinal" axis with subsequent development of chronic inflammation and immune disorders. Further study of the relationship between periodontal diseases and cancer opens up new prospects in the prevention, diagnosis and treatment of gastrointestinal cancer.

Periodontal disease is an inflammatory disease caused by pathogenic oral microorganisms that leads to the destruction of alveolar bone and connective tissues around the teeth. Although many studies have shown that periodontal disease is a risk factor for systemic diseases, such as type 2 diabetes and cardiovascular diseases, the relationship between nonalcoholic fatty liver disease (NAFLD) and periodontal disease has not yet been clarified. Thus, the purpose of this review was to reveal the relationship between NAFLD and periodontal disease based on epidemiological studies, basic research, and immunology. Many cross-sectional and prospective epidemiological studies have indicated that periodontal disease is a risk factor for NAFLD. An in vivo animal model revealed that infection with periodontopathic bacteria accelerates the progression of NAFLD accompanied by enhanced steatosis. Moreover, the detection of periodontopathic bacteria in the liver may demonstrate that the bacteria have a direct impact on NAFLD. Furthermore, Porphyromonas gingivalis lipopolysaccharide induces inflammation and accumulation of intracellular lipids in hepatocytes. Th17 may be a key molecule for explaining the relationship between periodontal disease and NAFLD. In this review, we attempted to establish that oral health is essential for systemic health, especially in patients with NAFLD.

The worldwide increase in nonalcoholic fatty liver disease (NAFLD) is a major public health problem. Obesity and diabetes are risk factors for NAFLD and the development of liver fibrosis is a risk factor for liver cancer. Periodontal disease bacteria can also exacerbate NAFLD. We previously reported that amazake, a traditional Japanese fermented food, improves the quality of life (QOL) of patients with liver cirrhosis. In this study, we investigated the effect of amazake intake on NAFLD patients with periodontal disease. Ten patients (mean age: 57.1 ± 19.2 years) consumed 100 g of amazake daily for 60 days. On days 0 and 60, their body mass index (BMI), body fat percentage, serum biochemical parameters, periodontal disease bacteria in saliva, and ten visual analog scales (VASs), namely, sense of abdomen distension, edema, fatigue, muscle cramps, loss of appetite, taste disorder, constipation, diarrhea, depression, and sleep disorder, were measured. For periodontal bacteria, the numbers of six types of bacteria in saliva (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Fusobacterium necleatum) and P. gingivalis-specific fimA genotype were determined. After 60 days of amazake consumption, eosinophils (p < 0.05), immune reactive insulin (IRI) (p < 0.01), and HOMA-IR (p < 0.05) had significantly increased and tumor necrosis factor α (TNFα) (p < 0.01), muscle cramps (p < 0.05), and depression (p < 0.05) had significantly decreased. All subjective symptoms improved after amazake intake. No change was observed in the periodontal bacteria. In conclusion, amazake significantly decreased TNFα and improved the QOL of the patients with NAFLD and periodontitis. However, caution should be exercised because amazake, which is manufactured using techniques that lead to concentrations of glucose from the saccharification of rice starch, may worsen glucose metabolism in NAFLD patients. Amazake may be an effective food for improving the symptoms of a fatty liver if energy intake is regulated.

Research and publications over the past decade have radically changed traditional medical concepts and our understanding of the possible relationship between organs and body systems. So, many studies are devoted to the study of the relationship between the intestinal microbiome and various diseases. The microbiome of the oral cavity has a certain effect on the intestinal microbiome. This review, based on published sources from the Pubmed and Scopus databases, which examined the relationship between periodontal microbiota/periodontal diseases and gastroenterological diseases, presents an expanded version of the report at the round table of the Scientific Society of Gastroenterologists of Russia on June 20, 2025. Within the framework of the hypothetical “journey” of the periodontal microbiota on the “periodontal-gastroenterological express” along the route mouth-intestine, the possible influence of the periodontal microbiota and periodontal diseases on the development of gastroenterological diseases is considered. The results of epidemiological, experimental and clinical studies indicate that periodontopathic bacteria can participate in the development of cancer of the gastrointestinal tract, peptic ulcer, inflammatory bowel disease and non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has been increasingly identified in patients with inflammatory bowel disease (IBD). We aimed to determine risk factors of NAFLD in patients with IBD. We examined 3 groups of patients: IBD + NAFLD, IBD only, and NAFLD only. Data on demographics, body mass index, duration of IBD, type of medication use, laboratory data, and metabolic risk factors were collected. A total of 168 patients between the ages 19 and 82 were evaluated, 56 patients in each group. Patients with IBD + NAFLD were significantly older than IBD only patients 45.0 (±14.1) versus 35.0 (±13), P = 0.007, and their mean body mass index was higher 30.4 (±10.2) versus 25.6 (±6.4); P = 0.002. IBD + NAFLD patients in comparison with IBD only patients had significantly longer duration of IBD (20 [±12.2] versus 10 [±7.7], P = 0.004), had an increased risk of diabetes (16% versus 2%, P = 0.01), and obesity (40% versus 20%, P = 0.02). There were no differences in the mean age or the mean body mass index (32.6 versus 30.4, P = 0.07) between patients with IBD + NAFLD and NAFLD only. More patients were obese in the NAFLD only group compared with the IBD + NAFLD group (59% versus 40%, P = 0.03), had hypertension (55% versus 33%, P = 0.02), hyperlipidemia (53% versus 17.5%, P = 0.0001), and diabetes (40% versus 16%, P = 0.0001). IBD patients with NAFLD had longer disease duration of IBD and developed NAFLD with fewer metabolic risk factors than patients with NAFLD only. These findings suggest that there may be other factors that contribute to the development of NAFLD in the IBD population.

Biomarkers in Fatty Liver Disease—Here is the Skinny

Increasing evidence indicates that chronic inflammation due to periodontal disease is associated with progression of non-alcoholic fatty liver disease (NAFLD) caused by a Western diet. NAFLD has also been associated with oral infection with the etiological agent of periodontal disease, Porphyromonas gingivalis. P. gingivalis oral infection has been shown to induce cardiometabolic disease features including hepatic lipid accumulation while also leading to dysbiosis of the gut microbiome. However, the impact of P. gingivalis infection on the gut microbiota of mice with diet-induced NAFLD and the potential for those changes to mediate NAFLD progression has yet to be determined. In the current study, we have demonstrated that P. gingivalis infection induced sustained alterations of the gut microbiota composition and predicted functions, which was associated with the promotion of NAFLD in steatotic mice. Reduced abundance of short-chain fatty acid-producing microbiota was observed after both acute and chronic P. gingivalis infection. Collectively, our findings demonstrate that P. gingivalis infection produces a persistent change in the gut microbiota composition and predicted functions that promotes steatosis and metabolic disease.

At the beginning of the 21st century, the concept of "periodontal medicine" was formed, which considers the bidirectional relationship between periodontal pathology and systemic diseases of the body. We searched the PubMed and Scopus information databases for sources published before 01.11.2024, which considered the relationship between periodontal pathology and oncological diseases. In the current review, we focused on the general epidemiological aspects of cancer and periodontal diseases, and possible mechanisms for the identified relationship between periodontal diseases and oncological diseases. Most of the sources found relate to the last decade, which indicates the relevance of analyzing the relationship between periodontal diseases and oncological diseases. Epidemiological studies and cancer control studies devoted to the study of the relationship between periodontal diseases and cancer risk suggest a positive association with the overall risk of cancer and some specific types of cancer. Possible mechanisms linking periodontal disease and cancer suggest translocation of periodontal bacteria, primarily potential carcinogens Porphyromonas gingivalis and Fusobacterium nucleatum, via the hematogenous route or the "mouth – gastrointestinal tract" axis, with subsequent development of chronic inflammation and immune system disorders. Further study of the relationship between periodontal disease and cancer opens up new perspectives in the prevention, diagnosis, and treatment of oncological diseases.