Preclinical and human studies have demonstrated the link between unbalanced gut microbiota and Alzheimer’s Disease (AD). However, there is still a lot of debate about how metabolic pathways are involved. Evidence indicates that neurodegenerative disorders are often associated with metabolic dysfunction, such as deregulation of lipid homeostasis, which may worsen neurological symptoms and contribute to AD progression. However, mechanistic insights into the link between abnormal lipid metabolism and beta-amyloid aggregation and clearance are unavailable.

Several studies describe the cholesterol-lowering effects of probiotics in both animals and humans. Bonfili and colleagues explored the effects of Slab51 on lipid metabolism in a mice model of the disease(1). Previous results from the team demonstrated that long-term supplementation with Slab51 in 3xTg-AD mice positively affected glucose metabolism, inflammatory and oxidative status and partially recovered the impaired neuronal proteolysis, finally improving cognitive abilities, with the consequent delay of AD progression (2-4).

This most recent work published in Clinical Nutrition investigated how microbiota modulation through probiotics can affect lipid composition in the same animal model. Results showed that Slab51 inhibited hepatic lipogenesis and cholesterol biosynthesis and qualitatively improved plasma lipid composition, consequently reducing total cholesterol/HDL-C and LDL-C/HDL-C ratios. The authors highlighted a plasmatic increase in arachidonic acid representing one key metabolite in the interactions among probiotic-induced lipid profile changes, insulin sensitivity, and inflammation.

This specific probiotic formulation also ameliorated the omega6/omega3 ratio, which results in unbalanced during inflammation-associated diseases, such as diabetes, obesity, mental disorders, cardiovascular and autoimmune diseases.

This evidence clarifies the currently unclear mechanisms through which microbiota can affect specific AD characteristics and suggests that modulating the gut microbiota with the probiotic Slab51 can positively affect the brain oxidative and inflammatory status by regulating plasma lipid profile, cholesterol biosynthesis, and bile acid synthesis.

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  1. Bonfili L, Cuccioloni M, Gong C, Cecarini V, Spina M, Zheng Y, Angeletti M, Eleuteri AM: Gut microbiota modulation in Alzheimer’s disease: focus on lipid metabolism. Clinical Nutrition 41(2022) 698-708. doi: https://doi.org/10.1016/j.clnu.2022.01.025
  2. Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasuti C, Fiorini D, Boarelli MC, Rossi G, Eleuteri AM: Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep 2017, 7:2426. doi: https://doi.org/10.1038/s41598-017-02587-2
  3. Bonfili L, Cecarini V, Cuccioloni M, Angeletti M, Berardi S, Scarpona S, Rossi G, Eleuteri AM: Slab51 probiotic formulation activates sirt1 pathway promoting antioxidant and neuroprotective effects in an ad mouse model. Mol Neurobiol 2018, 55:7987-8000. doi: https://doi.org/10.1007/s12035-018-0973-4
  4. Bonfili L, Cecarini V, Gogoi O, Berardi S, Scarpona S, Angeletti M, Rossi G, Eleuteri AM: 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: https://doi.org/10.1016/j.neurobiolaging.2019.11.004

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