Probiotics Fermentation Technology, a Novel Kefir Product, Ameliorates Cognitive Impairment in Streptozotocin‐Induced Sporadic Alzheimer’s Disease in Mice

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Gut microbiota dysfunction (dysbiosis) is implicated in the pathology of AD and is associated with several detrimental consequences, including neurotransmitter depletion, oxidative stress, inflammation, apoptosis, and insulin resistance, which all contribute to the onset of AD. The objective of this study was to assess the effectiveness of Probiotics Fermentation Technology (PFT), a kefir product, in alleviating AD symptoms via regulation of the gut microbiota using a streptozotocin- (STZ-) induced AD mouse model and to compare its activity with simvastatin, which has been proven to effectively treat AD. Mice received one intracerebroventricular injection of STZ (3 mg/kg). PFT (100, 300, 600 mg/kg) and simvastatin (20 mg/kg) were administered orally for 3 weeks. PFT supplementation mitigated STZ-induced neuronal degeneration in the cortex and hippocampus, restored hippocampal acetylcholine levels, and improved cognition in a dose-dependent manner. These effects were accompanied by reductions in oxidative damage, proinflammatory cytokine expression, apoptosis, and tau hyperphosphorylation. Moreover, PFT hindered amyloid plaque accumulation via the enhancement of insulin-degrading enzyme. These beneficial effects were comparable to those produced by simvastatin. The results suggest that PFT can alleviate AD symptoms by regulating the gut microbiota and by inhibiting AD-related pathological events.

The Emerging Scenario of the Gut–Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases

“…In summary, the beneficial effects of kefir are associated with its anti-inflammatory and antioxidant properties, as previously demonstrated by us and others [ 40 , 163 , 212 ], preventing apoptosis and, consequently, neuronal degeneration [ 213 , 214 ]. Therefore, this probiotic beverage shows the potential to act as an adjuvant in conventional therapies addressing ND.…”

Naringin Protects against Tau Hyperphosphorylation in Aβ25–35-Injured PC12 Cells through Modulation of ER, PI3K/AKT, and GSK-3β Signaling Pathways

“…Aβ [25][26][27][28][29][30][31][32][33][34][35] . Next, we used PC12 cells to further study the indepth mechanism of naringin's neuroprotective effect.…”

“…Hyperphosphorylated Tau leads to increased Aβ production; in turn, Aβ accumulation can also increase the activity of GSK-3β [27].…”

“…[25][26][27][28][29][30][31][32][33][34][35] . As expected, the viability of PC12 cells treated with 20 M Aβ 25-35 was significantly lower than that of untreated cells, and the cyto-toxic effect of Aβ 25-35 was abrogated by E 2 pretreatment (Figure 4(b)).…”

Novel Nutraceutical Compounds in Alzheimer Prevention

“…Kefir is a dairy product similar to liquid yogurt, is obtained through the fermentation due to the action of a group of yeasts (fungi) and bacteria ( lactobacilli ) [ 75 ]. Recently, the beneficial effects of kefir in AD were assessed: it was demonstrated that kefir ameliorates cognitive impairment in streptozotocin induced mice model of AD [ 76 ]. The latter would be explained, at least in part, by the gut microbiome modulation and enhancement of the insulin/PI3K/Akt pathway, which was demonstrated in another model of sporadic AD [ 77 ].…”