Table 1.
Impact of periodontal bacteria on systemic diseases via the oral-gut axis.
| Systemic Diseases | Periodontal Bacteria | Possible Pathogenic Mechanisms Through the Oral-gut Axis | Impact on Systemic Diseases |
|---|---|---|---|
| Inflammatory Bowel Disease (IBD) | P. gingivalis, F. nucleatum, P. intermedia | (i) compromise the intestinal barrier (downregulation of TJs), enhance intestinal immune responses (e.g. induction of M2 macrophage polarization), and affect intestinal metabolism (e.g. decreased unsaturated fatty acid synthesis and increased arachidonic acid metabolism) | Promote the development of IBD and exacerbate the progression of pre-existing IBD |
| (ii) Induction and migration of oral pathobiont-reactive Th17 cells indirectly exacerbate intestinal inflammation. | |||
| Colorectal Cancer (CRC) | P. gingivalis, F. nucleatum | exploit tumor surface barrier defects, invade normal colonic tissue and induce local inflammation, while producing genotoxic metabolites to induce oncogenic transformation of colonic epithelial cells. | Promote tumor progression, metastasis and recurrence |
| Rheumatoid Arthritis (RA) | P. gingivalis, P. intermedia, A. actinomycetemcomitans, F. nucleatum, P. nigrescens | (i) Increased production of pro-inflammatory factors (e.g. IL-6) and citrullinated protein in joint and intestinal tissues disrupts immune tolerance in susceptible individuals. | Exacerbate the severity of joint destruction and affect regression on anti-rheumatic drugs |
| (ii) trigger synovial inflammation by activating the FadA-Rab5a-YB-1 axis in synovial macrophages. | |||
| (iii) inflammatory bone destruction by increasing the intestinal hyperimmune response triggered by Th17 cellular immune responses. | |||
| Alzheimer’s Disease (AD) | P. gingivalis, T. denticola | Promote neuroinflammation and neurodegeneration by disrupting the intestinal barrier and BBB. This includes inducing Aβ plaque formation through activation of the TLR4/NF-κB and MAPK pathways, proteolysis of tau and subsequent NFTs formation through activation of caspase-3, and neuronal death through triggering of the immune cascade response. | Increase risk of developing AD and increased dementia severity (e.g. cognitive impairment) |
| Parkinson’s Disease (PD) | P. gingivalis | (i) Disrupt the intestinal barrier and BBB and activate the TLR4/MyD88/NF-κB pathway in the SN and colon, ultimately leading to dopaminergic neuronal damage and microglia activation in the SNpc. | Increase risk of developing PD and correlate with disease severity |
| (ii) Induce misfolding and aggregation of α-synuclein in specific enteric neurons and subsequent migration to the brain. | |||
| Autism Spectrum Disorder (ASD) | P. gingivalis | (i) Disrupt the intestinal barrier and BBB, triggering the microglia-associated NF-κB pathway to induce neuroinflammation. | Correlate with ASD severity |
| (ii) Promote mitochondrial dysfunction, resulting in alterations in metabolism and neurosignaling activities. | |||
| Major Depressive Disorder (MDD) | P. gingivalis, F. nucleatum, A. actinomycetemcomitans | (i) Disrupt the intestinal barrier and the BBB, leading to high activation of astrocytes and promoting neuroinflammation and neuronal death. | increase risk of developing MDD, induce depression-like behavior and correlate with disease severity |
| (ii) potential association on the transcriptomic level. | |||
| Liver Disease | P. gingivalis, A. actinomycetemcomitans, T. denticola | activate the PRR via the oral-gut-liver axis (e.g. portal circulation) and act directly on hepatocytes, Kupffer cells and HSC, triggering downstream pro-inflammatory cascades and ultimately inflammation and fibrosis in the liver. | affect the prevalence, mortality, disease severity and prognosis of many chronic liver diseases (e.g. NAFLD, NASH and cirrhosis) |
| Obesity | P. gingivalis, A. actinomycetemcomitans, T. forsythia | (i) induce insulin resistance, hepatic steatosis and macrophage infiltration in adipose tissue. | Increase the risk of obesity, correlate with disease severity, and affect regulation of energy use and metabolism in vivo |
| (ii) Induced endotoxemia may alter endocrine function and gene expression in BAT. | |||
| (iii) affect the secretion of pro/anti-inflammatory adipokines. | |||
| Diabetes Mellitus (DM) | P. gingivalis, A. actinomycetemcomitans, T. forsythia, F. alocis | induce/exacerbate insulin resistance and glucose intolerance by mediating entero-hepatic metabolic derangements. | Increase the risk of developing DM and affect glycemic control in DM patients |
| Atherosclerotic Cardiovascular Disease (ASCVD) | P. gingivalis, A. actinomycetemcomitans, T. denticola, T. forsythia, F. nucleatum, P. intermedia | (i) modulate the production of bioactive metabolites (e.g. TMAO) from the gut microbiota and influence atherosclerotic plaque formation and progression. | Increase the risk of ASCVD, promote inflammatory and atherosclerotic changes in blood vessels. |
| (ii) induce the recruitment of macrophages and their infiltration of adipose tissue, culminating in the formation of foam cells that accumulate in the artery walls. | |||
| Skin disease | P. gingivalis, A. actinomycetemcomitans, P. intermedia, T. denticola, T. forsythia, P. nigrescens | modulate autoimmune and allergic skin diseases through immune (e.g. Th17/Treg balance), metabolic, and neuroendocrine pathways. | correlate with severity of skin disease |