Oral infection with <i>P. gingivalis</i> exacerbates autoimmune encephalomyelitis

Polak, David; Shmueli, Aviv; Brenner, Talma; Shapira, Lior

doi:10.1002/jper.17-0531

Cited by 12 publications

(8 citation statements)

References 36 publications

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“…However, this is, in our best knowledge, the first study describing the presence of F. nucleatum in brain tissues. Periodontitis induction with P. gingivalis not only has led to microbiological changes in the brain, but also to experimental exacerbation of other central nervous system diseases (Polak et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Periodontal diseases and depression: A pre‐clinical in vivo study

Martínez

Martín-Hernández

Virto³

et al. 2021

J Clinic Periodontology

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Aim: To analyse, through a pre-clinical in vivo model, the possible mechanisms linking depression and periodontitis at behavioural, microbiological and molecular levels.Materials and methods: Periodontitis (P) was induced in Wistar:Han rats (oral gavages with Porphyromonas gingivalis and Fusobacterium nucleatum) during 12 weeks, followed by a 3-week period of Chronic Mild Stress (CMS) induction. Four groups (n = 12 rats/group) were obtained: periodontitis and CMS (P+CMS+); periodontitis without CMS; CMS without periodontitis; and control. Periodontal clinical variables, alveolar bone levels (ABL), depressive-like behaviour, microbial counts and expression of inflammatory mediators in plasma and brain frontal cortex (FC), were measured.ANOVA tests were applied. Results:The highest values for ABL occurred in the P+CMS+ group, which also presented the highest expression of pro-inflammatory mediators (TNF-α, IL-1β and NF-kB) in frontal cortex, related to the lipoprotein APOA1-mediated transport of bacterial lipopolysaccharide to the brain and the detection of F. nucleatum in the brain parenchyma. A dysregulation of the hypothalamic-pituitary-adrenal stress axis, reflected by the increase in plasma corticosterone and glucocorticoid receptor levels in FC, was also found in this group. Conclusions:Neuroinflammation induced by F. nucleatum (through a leaky mouth) might act as the linking mechanism between periodontal diseases and depression.

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Section: Discussionmentioning

confidence: 99%

“…Periodontitis induction with P. gingivalis not only has led to microbiological changes in the brain, but also to experimental exacerbation of other central nervous system diseases (Polak et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Periodontal diseases and depression: A pre‐clinical in vivo study

Martínez

Martín-Hernández

Virto³

et al. 2021

J Clinic Periodontology

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“…In support of this view, the administration of P. gingivalis has been shown to alter the gut microbial composition and suppress the expression of TJ-related proteins, thereby augmenting the systemic translocation of bacteria and their products (84,85). The administration of P. gingivalis accelerates metabolic syndrome, collagen-induced arthritis, and experimental autoimmune encephalomyelitis (EAE) (84,86,87). Another oral microbe, Fusobacterium nucleatum, also induces intestinal dysbiosis and LGS by suppressing the expression of both ZO-1 and occluding.…”

Section: Barrier Disruption By Specific Microbesmentioning

confidence: 99%

Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity

2021

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The intestinal surface is constitutively exposed to diverse antigens, such as food antigens, food-borne pathogens, and commensal microbes. Intestinal epithelial cells have developed unique barrier functions that prevent the translocation of potentially hostile antigens into the body. Disruption of the epithelial barrier increases intestinal permeability, resulting in leaky gut syndrome (LGS). Clinical reports have suggested that LGS contributes to autoimmune diseases such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and celiac disease. Furthermore, the gut commensal microbiota plays a critical role in regulating host immunity; abnormalities of the microbial community, known as dysbiosis, are observed in patients with autoimmune diseases. However, the pathological links among intestinal dysbiosis, LGS, and autoimmune diseases have not been fully elucidated. This review discusses the current understanding of how commensal microbiota contributes to the pathogenesis of autoimmune diseases by modifying the epithelial barrier.

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“…Oral administration of P. gingivalis 3×/wk for 1 mo in mice P. gingivalis impaired cognition associated with gut dysbiosis, neuroinflammation, and glymphatic dysfunction (Chi et al 2021). MS mouse model received control, subcutaneous, or oral gavage of P. gingivalis Infection with P. gingivalis had significantly greater maximal clinical scores of autoimmune encephalomyelitis compared to control (Polak et al 2018). CP induced with ligature and control CP mice exhibited significant neuronal loss in cortex, reduction of synaptophysin in hippocampus and cortex, increase of proinflammatory cytokine levels, disruption of the BBB, gut microbiota dysbiosis, and systemic inflammation (Xue et al 2020).…”

Section: Elderly Cognitively Normal Subjectsmentioning

confidence: 95%

“…The study recorded microglial activation, increased expression of inducible nitric oxide synthase (iNOS), and IL-1β in addition to an increase in axonal injury by which an association between peripheral inflammation and increased levels of circulating cytokines with deterioration of axons in the rodent model of MS was shown (Moreno et al 2011). Polak et al (2018) studied a mouse model of MS by exposure to myelin oligodentrocyte glycoprotein (MOG), in which either subcutaneous or oral infection with P. gingivalis aggravated MS pathology with an increase in proliferation of lymphocytes and clinical symptoms, such as weakness of the limbs and tail, palsy, and other signs of disease. Both experiments suggest that pathological MS symptoms might be related to peripheral inflammation due to the presence of periodontal bacteria.…”

Section: Periodontitis and Neurodegenerative Diseasesmentioning

confidence: 99%

Neuroinflammation: A Distal Consequence of Periodontitis

Kiprowska

Kansara

et al. 2022

J Dent Res

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Periodontitis, a chronic, inflammatory disease, induces systemic inflammation and contributes to the development of neurodegenerative diseases. The precise etiology of the most common neurodegenerative disorders, such as sporadic Alzheimer’s, Parkinson’s diseases and multiple sclerosis (AD, PD, and MS, respectively), remains to be revealed. Chronic neuroinflammation is a well-recognized component of these disorders, and evidence suggests that systemic inflammation is a possible stimulus for neuroinflammation development. Systemic inflammation can lead to deleterious consequences on the brain if the inflammation is sufficiently severe or if the brain shows vulnerabilities due to genetic predisposition, aging, or neurodegenerative diseases. It has been proposed that periodontal disease can initiate or contribute to the AD pathogenesis through multiple pathways, including key periodontal pathogens. Dysbiotic oral bacteria can release bacterial products into the bloodstream and eventually cross the brain-blood barrier; these bacteria can also cause alterations to gut microbiota that enhance inflammation and potentially affect brain function via the gut–brain axis. The trigeminal nerve has been suggested as another route for connecting oral bacterial products to the brain. PD and MS are often preceded by gastrointestinal symptoms or aberrant gut microbiome composition, and alterations in the enteric nervous system accompany the disease. Clinical evidence has suggested that patients with periodontitis are at a higher risk of developing PD and MS. This nexus among the brain, periodontal disease, and systemic inflammation heralds new ways in which microglial cells, the main innate immune cells, and astrocytes, the crucial regulators of innate and adaptive immune responses in the brain, contribute to brain pathology. Currently, the lack of understanding of the pathogenesis of neurodegeneration is hindering treatment development. However, we may prevent this pathogenesis by tackling one of its possible contributors (periodontitis) for systemic inflammation through simple preventive oral hygiene measures.

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Oral infection with P. gingivalis exacerbates autoimmune encephalomyelitis

Cited by 12 publications

References 36 publications

Periodontal diseases and depression: A pre‐clinical in vivo study

Periodontal diseases and depression: A pre‐clinical in vivo study

Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity

Neuroinflammation: A Distal Consequence of Periodontitis

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