Porphyromonas gingivalis (P. gingivalis) is one of the pathogens involved in gingival inflammation, which may trigger neuroinflammatory diseases such as Alzheimer’s disease (AD). This study aimed to investigate the protective (preventive and treatment) effects of a lactobacilli mixture combining Lactobacillus reuteri PTCC1655, Lactobacillus brevis CD0817, Lacticaseibacillus rhamnosus PTCC1637, and Lactobacillus plantarum PTCC1058 against P. gingivalis-induced gingival inflammation and AD-like pathology in rats. These probiotic strains exhibited cognitive enhancement effects, but this study proposed to assess their activity in a mixture. To propose a probable mechanism for P. gingivalis cognitive impairments, the TEs balance were analyzed in hippocampus and cortex tissues. Animals were divided into five groups: the control, lactobacilli, P. gingivalis, lactobacilli + P. gingivalis (prevention), and P. gingivalis + lactobacilli group (treatment) groups. The behavioral and histopathological changes were compared among them. Finally, The Trace elements (TEs) levels in the hippocampus and cortex tissues were analyzed. The palatal tissue sections of the P. gingivalis infected rats showed moderate inflammation with dense infiltration of inflammatory cells, a limited area of tissue edema, and vascular congestion. Additionally, passive avoidance learning and spatial memory were impaired. Histopathological tests revealed the presence of Aβ-positive cells in the P. gingivalis group. While the Aβ-positive cells decreased in the treatment group, their formation was inhibited in the preventive group. Administration of a mixture of lactobacilli (orally) effectively mitigated the gingival inflammation, Aβ production, and improved learning and memory functions. Moreover, Zn, Cu, and Mn levels in the hippocampus were dramatically elevated by P. gingivalis infection, whereas lactobacilli mixture mitigated these disruptive effects. The lactobacilli mixture significantly prevented the disruptive effects of P. gingivalis on gingival and brain tissues in rats. Therefore, new formulated combination of lactobacilli may be a good candidate for inhibiting the P. gingivalis infection and its subsequent cognitive effects. The current study aimed to evaluate the effects of a lactobacilli mixture to manage the disruptive effects of P. gingivalis infection on memory.
