Background: Intestinal bacteria-derived molecules, such as lipopolysaccharide (LPS) produced by Gram-negative bacteria, can translocate into the bloodstream through the gut wall, contributing to inflammation and neurodegeneration via oxidative stress mechanisms. NADPH oxidase-2 activation and superoxide anion production play a key role in this process, particularly in conditions like Alzheimer's disease (AD), where gut permeability is often altered. This study hypothesized that modulating gut microbiota with the probiotic Escherichia coli Nissle 1917 (ECN) could mitigate LPS translocation and its associated inflammatory effects. Objective: To evaluate the effect of daily ECN administration on serum LPS levels in elderly AD patients. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 40 mild AD patients, with 39 completing the study (20 ECN, 19 placebo). Participants received ECN (2.5–25 × 10^9 CFU/capsule) or placebo for six weeks. The serum activity of soluble NOX2-dp (sNOX2-dp), hydrogen peroxide (H ₂ O ₂ ) production, tumor necrosis factor (TNF)-α levels and LPS was evaluated, while serum zonulin levels were measured to assess gut permeability. Results: The ECN group showed significant reductions in sNOX2-dp (−21%), H ₂ O ₂ (−27%), TNF-α (−18%), LPS (−15%), and zonulin (−35%), along with improved Mini-Mental State Examination (MMSE) scores. No significant changes were seen in the placebo group. Mixed ANOVA showed significant time-by-treatment interactions for zonulin (p = 0.04) and MMSE (p < 0.001). Changes in LPS correlated with changes in zonulin (Rs = 0.408, p = 0.011). Conclusions: ECN may strengthen gut barrier function, reduce endotoxemia, and attenuate inflammation in AD, though larger studies are needed to confirm these findings.

Background: Exposure to tobacco smoke, from conventional tobacco cigarettes (CTC) or heated tobacco products (HTPs), increases oxidative stress, causing endothelial dysfunction and higher cardiovascular risk. It is unclear whether smoke exposure also promotes low-grade endotoxemia, potentially activating NADPH oxidase and further impairing endothelial function. This study assessed serum lipopolysaccharide (LPS) levels in children and adults actively or passively exposed to conventional cigarette smoke or HTPs, compared with non-exposed controls. Methods: We conducted a cross-sectional study comprising 26 children passively exposed to HTPs, 26 children exposed to CTC, and 26 unexposed controls, as well as 20 adult chronic HTP users, 20 chronic CTC, and 20 non-smoking adults. Circulating LPS was measured alongside oxidative stress markers (NOX2, H₂O₂), endothelial function, intestinal permeability (zonulin), and nicotine exposure (serum cotinine). Results: Exposed children had higher cotinine, LPS, and zonulin than controls, with no differences between HTP and CTC groups. Multiple linear regression analysis identified cotinine (β = 0.343; p = 0.005) and zonulin (β = 0.441; p < 0.001) as independent LPS predictors. In adults, LPS and zonulin were higher in both smoker groups versus controls; zonulin (β = 0.477; p < 0.001) and nitric oxide bioavailability (β = −0.307; p = 0.007) independently predicted LPS. Conclusions: Passive and active exposure to CTC or HTPs increases low-grade endotoxemia and zonulin, potentially driving NOX2-mediated oxidative stress.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), unlike pediatric acute-onset neuropsychiatric syndrome (PANS), is triggered by infections. This study aimed to assess the differences in low-grade endotoxemia and oxidative stress between these conditions. A cross-sectional study compared serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes, lipopolysaccharide (LPS), and zonulin in 30 PANDAS, 21 PANS, and 30 control (CT) children matched for age and gender. Zonulin was used to assess gut permeability. Patients with PANDAS showed significantly higher serum levels of sNOX2-dp, isoprostanes, LPS, and zonulin than PANS and controls, while no significant differences were found between PANS and controls. sNOX2-dp correlated with isoprostanes (Rs = 0.708; p < 0.001), LPS (Rs = 0.584; p < 0.001), and zonulin (Rs = 0.662; p < 0.001). Multiple regression identified isoprostanes (β = 0.599; p < 0.001) and zonulin (β = 0.295; p = 0.01) as independent predictors of sNOX2-dp (R² = 81%). PANDAS and PANS showed distinct profiles of LPS, zonulin, NOX2, and isoprostanes. Future research should explore therapies targeting endotoxemia and oxidative stress for potential clinical benefits.