| Summary: | Previous studies have reported an association between oral microbial dysbiosis and the development and progression of pathologies in the central nervous system. <i>Porphyromonas gingivalis</i> (<i>Pg</i>), the keystone pathogen of the oral cavity, can induce a systemic antibody response measured in patients’ sera using enzyme-linked immunosorbent assays. The present case–control study quantified the immune system’s response to <i>Pg</i> abundance in the oral cavities of patients affected by different central nervous system pathologies. The study cohort included 87 participants: 23 healthy controls (HC), 17 patients with an acute neurological condition (N-AC), 19 patients with a chronic neurological condition (N-CH), and 28 patients with neurodegenerative disease (N-DEG). The results showed that the <i>Pg</i> abundance in the oral cavity was higher in the N-DEG patients than in the HC (<i>p</i> = 0.0001) and N-AC patients (<i>p</i> = 0.01). In addition, the <i>Pg</i> abundance was higher in the N-CH patients than the HCs (<i>p</i> = 0.005). Only the N-CH patients had more serum anti-<i>Pg</i> antibodies than the HC (<i>p</i> = 0.012). The inadequate response of the immune system of the N-DEG group in producing anti-<i>Pg</i> antibodies was also clearly indicated by an analysis of the ratio between the anti-<i>Pg</i> antibodies quantity and the <i>Pg</i> abundance. Indeed, this ratio was significantly lower between the N-DEG group than all other groups (<i>p</i> = 0.0001, <i>p</i> = 0.002, and <i>p</i> = 0.03 for HC, N-AC, and N-CH, respectively). The immune system’s response to <i>Pg</i> abundance in the oral cavity showed a stepwise model: the response diminished progressively from the patients affected with an acute condition to the patients suffering from chronic nervous system disorders and finally to the patients affected by neurodegenerative diseases.
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