Interaction between serum levels of Porphyromonas gingivalis immunoglobulin G and lutein/zeaxanthin is associated with risk for age-related macular degeneration

Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiota. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiota and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis. To investigate the potential association between periodontopathic microbiota and AMD occurrence, we conducted a candidate microbe approach case-control study in the Third National Health and Nutrition Examination Survey (NHANES-III). Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Consistent with current evidence that host nutritional status critically modulates immune responses to the microbiota and influences human health, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 µmol/L or ≥ 20 µg/dL) might potentially mitigate the P. gingivalis-related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrients related to eye health and humoral response to P. gingivalis.Significance statement: While humoral response to P. gingivalis indicates an impact on age-related macular degeneration, nutritional factors may modulate the associated risk.