Oxidative Stress and Dementia in Alzheimer’s Patients: Effects of Synbiotic Supplementation

Abstract

Background. Alzheimer’s disease (AD) is the most common cause of dementia in elderly patients. Recently, several studies have shown that inflammation and oxidative stress precede the cardinal neuropathological manifestations of AD. In view of the proven antioxidant effects of probiotics, we proposed that continuous dietary supplementation with milk fermented with kefir grains might improve cognitive and metabolic and/or cellular disorders in the AD patients. Methods. This study was designed as an uncontrolled clinical investigation to test the effects of probiotic-fermented milk supplementation (2 mL/kg/daily) for 90 days in AD patients exhibiting cognitive deficit. Cognitive assessment, cytokine expression, systemic oxidative stress levels, and blood cell damage biomarkers were evaluated before (T0) and after (T90) kefir synbiotic supplementation. Results. When the patients were challenged to solve 8 classical tests, the majority exhibit a marked improvement in memory, visual-spatial/abstraction abilities, and executive/language functions. At the end of the treatment, the cytometric analysis showed an absolute/relative decrease in several cytokine markers of inflammation and oxidative stress markers (⋅O2–, H2O2, and ONOO−, ~30%) accompanied by an increase in NO bioavailability (100%). In agreement with the above findings by using the same technique, we observed in a similar magnitude an improvement of serum protein oxidation, mitochondrial dysfunction, DNA damage/repair, and apoptosis. Conclusion. In conclusion, we demonstrated that kefir improves cognitive deficits, which seems to be linked with three important factors of the AD—systemic inflammation, oxidative stress, and blood cell damage—and may be a promising adjuvant therapy against the AD progression.

Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation With Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics

“…In a double-blind, randomized, placebo-controlled trial in 30 patients with AD, subjects were provided a probiotic containing Lactobacillus acidophilus , Lactobacillus casei , Bifidobacterium bifidum and Lactobacillus fermentum or no treatment in disease-matched control subjects for 12 weeks. 160 A significant increase in learning and memory as measured with the Mini-Mini-Mental State Examination (MMSE) test and decrease in malondialdehyde, a marker of oxidative stress, was observed in the probiotic compared to placebo group. Probiotic treatment also improved Beta cell function and reduced serum high-sensitivity C-reactive protein (hs-CRP), insulin resistance, and serum triglycerides in the probiotic group.…”

Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current Perspective

“…The exact pathological mechanism of AD has not been confirmed yet, but there are several factors involved in the systematic pathogenesis. These include increased intestine barrier permeability, higher proinflammatory cytokines production, and impaired mitochondrial functionality, leading to excessive amounts of reactive oxygen species and oxidation ( Ton et al, 2020 ).…”

“…The modulations of gut microbiota and metabolic butyrate are also key phenomena observed in this study. In terms of clinical trials, Ton et al (2020) assessed the efficacy of probiotic-based kefir intervention for 3 months in AD patients having cognitive impairments. The main biomarkers were oxidative stress levels, cytokine levels, cognitive impairment, and blood cell damage.…”

d-Galactose Decreases Anion Exchange Capability through Band 3 Protein in Human Erythrocytes

“…When oxidative stress persists, the excessive free radical species accumulation can influence many cellular signaling pathways and damage organic macromolecules, which can be oxidized [ 10 , 11 ]. The overproduction of oxidative stress is a common patho-physiological state underlying many chronic diseases, such as cardiovascular diseases [ 12 , 13 ], neurodegenerative diseases [ 14 ], cancer [ 15 ], metabolic disorders (diabetes mellitus [ 16 ]), and diseases related to aging [ 17 ], although the precise mechanisms contributing to the oxidative stress-induced damage are still under investigation. Several studies have exploited the in vivo exposure to d -Gal as a typical model for exploring the mechanisms underlying oxidative stress-related diseases in plasma or blood cells [ 6 , 18 , 19 , 20 , 21 ].…”