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).

These new results confirm that the probiotic formulation SLAB51 impacts gut function in AD mice, counteracts oxidation, reduces inflammation, and improves energy metabolism.

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  1. Ceccarelli, G.; Marazzato, M.; Celani, L.; Lombardi, F.; Piccirilli, A.; Mancone, M.; Trinchieri, V.; Pugliese, F.; Mastroianni, C.M.; d’Ettorre, G. Oxygen Sparing Effect of Bacteriotherapy in COVID-19. Nutrients 2021, 13, 2898. doi.org/10.3390/nu13082898
  2. Bonfili L, Gong C, Lombardi F, Cifone MG, Eleuteri AM Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1: Therapeutic Implication in Alzheimer’s Disease J. Mol. Sci. 2022, 23, 357. doi.org/10.3390/ijms23010357
  3. Bonfili, L.; Cecarini, V.; Berardi, S.; Scarpona, S.; Suchodolski, J.S.; Nasuti, C.; Fiorini, D.; Boarelli, M.C.; Rossi, G.; Eleuteri, A.M. Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci. Rep. 2017, 7, 2426. doi: 10.1038/s41598-017-02587-2.
  4. Bonfili, L.; Cecarini, V.; Cuccioloni, M.; Angeletti, M.; Berardi, S.; Scarpona, S.; Rossi, G.; Eleuteri, A.M. SLAB51 Probiotic Formulation Activates SIRT1 Pathway Promoting Antioxidant and Neuroprotective Effects in an AD Mouse Model. Neurobiol. 2018, 55, 7987–8000. doi: 10.1007/s12035-018-0973-4.
  5. Bonfili, L.; Cecarini, V.; Gogoi, O.; Berardi, S.; Scarpona, S.; Angeletti, M.; Rossi, G.; Eleuteri, A.M. Gut microbiota manipulation through probiotics oral administration restores glucose homeostasis in a mouse model of Alzheimer’s disease. Neurobiol. Aging 2020, 87, 35–43. doi: 10.1016/j.neurobiolaging.2019.11.004.

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