Abstract
Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in neurodegenerative pathologies. We report evidence that chronic supplementation with SLAB51 enhanced cerebral expression of HIF-1α and decreased levels of prolyl hydroxylase 2 (PHD2), an oxygen dependent regulator of HIF-1α degradation; moreover, it successfully counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels in AD mice. Altogether, the results demonstrate an additional mechanism through which SLAB51 exerts neuroprotective and anti-inflammatory effects in this model of AD.
Highlights
Gut dysbiosis is an established key player in the pathogenesis of Alzheimer’s diseases (AD) and, more generally, in age-related neurodegenerations
Nitric oxide (NO) production and oxidation are increased in the brains of AD subjects, contributing to neuronal cell loss and neurodegeneration [16]
SLAB51 restored the plasmatic nitrite concentration and inducible nitric oxide synthase (iNOS) protein expression in the brain of these animals (Figure 1), indicating downstream positive effects of these changes on the compromised inflammatory and oxidative status in AD. These results are in line with previously published evidence on the antioxidant effects of the probiotic
Summary
Gut dysbiosis is an established key player in the pathogenesis of Alzheimer’s diseases (AD) and, more generally, in age-related neurodegenerations. Oral bacteriotherapy is a new, appealing therapeutic approach to strategically modulate gut microbiota composition in order to counteract AD onset and progression, representing a debated issue [4]. In this context, the effects of the oral supplementation of SLAB51 multi-strain probiotic formulation were previously studied in a transgenic murine model of AD, demonstrating that this formulation can influence multiple neuro-chemical pathways, by increasing the plasma concentration of short chain fatty acids and neuroprotective gut hormones, restoring the impaired proteolytic pathways, triggering antioxidant mechanisms, and ameliorating energy homeostasis. AD animal model (3xTg-AD mice), supporting the neuroprotective effects of probiotics oral supplementation on neuroinflammation in AD
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