Lactobacillus Rhamnosus and Saccharomyces Boulardii Attenuate LPS-Induced Cognitive and Affective Dysfunction Associated with Hippocampal Neuroinflammatory and Neurochemical Alterations

Lipopolysaccharide (LPS)-induced endotoxemia is widely used to model neuroinflammation-associated cognitive impairment, primarily involving activation of Toll-like receptor 4 (TLR4) and downstream NF-κB signaling. This study investigated whether probiotic interventions with Saccharomyces boulardii or Lactobacillus rhamnosus attenuate LPS-induced neurobehavioral and molecular alterations. Male Wistar rats were exposed to subchronic intraperitoneal LPS (0.25 mg/kg/day, 9 days) with or without concurrent probiotic administration. Behavioral assessments included the open field, elevated plus maze, forced swim, and novel object recognition tests. Hippocampal levels of inflammatory (TLR4, NF-κB, TNF-α, IL-6, GFAP), neurotrophic (BDNF, CREB), cholinergic (ACh, AChE), and apoptotic (p53, BAX, caspase-3) markers were quantified by ELISA. LPS exposure was associated with increased hippocampal TLR4 and NF-κB p65 levels, elevated TNF-α and IL-6 levels, and higher GFAP levels, alongside reduced BDNF and CREB levels, an altered ACh/AChE balance, and increased levels of apoptosis-related proteins. These molecular alterations coincided with deficits in recognition memory and increased anxiety- and depressive-like behaviors without affecting locomotor activity. Both S. boulardii and L. rhamnosus significantly attenuated these changes, reducing inflammatory markers, improving neurotrophic and cholinergic parameters, and partially attenuating apoptosis-related proteins. Behavioral impairments were concurrently ameliorated. Overall, these findings suggest that LPS-induced cognitive and behavioral alterations are closely associated with coordinated inflammatory, neurochemical, and apoptotic changes in the hippocampus. Because both probiotics were administered prophylactically, these findings indicate preventive rather than therapeutic efficacy. As all molecular outcomes were quantified by ELISA in whole-hippocampus homogenates, they should be interpreted as changes in protein levels rather than as demonstrated pathway activation.