Gut dysbiosis is an established key player in the pathogenesis and/or development of age-related neurodegeneration, such as Alzheimer’s disease (AD). By altering the intestinal permeability and the blood-brain barrier, gut dysbiosis can promote neuroinflammation, oxidation, amyloid-beta deposition, insulin resistance, and neuronal degeneration. Oral bacteriotherapy represents a promising approach to strategically modulate gut microbiota composition and counteract the onset and progression of AD.
Evidence shows the hippocampus of AD subjects suffers from a reduction of blood oxygenation. The critical consequence of cerebral hypoxia is neuroinflammation. During hypoxia, the oxygen-regulated subunit HIF-1α forms a heterodimer with the constitutively expressed HIF-1β. The result affects the transcription of some crucial regulators of glucose homeostasis, cellular stress, inflammation, and apoptosis. Considering that hypoxia conditioning is a promising strategy to treat central nervous system diseases, any treatment that reduces oxygen consumption by intestinal cells thus implicating an increased oxygen supply to the brain becomes a possible approach for preventing AD.
A recent study in COVID-19 patients suggested that SLAB51 multi-strain probiotic formulation has an oxygen sparing effect (1). In this contest, Bonfili and colleagues report evidence that chronic supplementation with SLAB51 enhances cerebral expression of HIF-1α and decreases levels of prolyl hydroxylase 2 (PHD2), an oxygen-dependent regulator of HIF-1α degradation. In addition, this specific probiotic formulation counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels, indicating both an antioxidant and anti-inflammatory effect of SLAB51 (2).
These outcomes agree with previous data by the same authors after SLAB51 supplementation, i.e., the enriched gut concentration of anti-inflammatory bacterial metabolites and ameliorated oxidative status (3, 4). The increased HIF-1α also supports previously published data showing that SLAB51 augments the brain expression of glucose transporters 1 and 3 and enhances glucose uptake (5).