Effect of the probiotic Escherichia coli Nissle 1917 on serum levels of NADPH oxidase-2 and lipopolysaccharide in patients with Alzheimer's disease

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Abstract
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.
Funding Information
  • PNRR (PNRR—M4C2- I1.3 Project PE_00000019 “HEAL ITAL)

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