A peripheral signature of Alzheimer’s disease featuring microbiota-gut-brain axis markers

Alzheimer s Research & Therapy, Год журнала: 2023, Номер 15(1)

Опубликована: Май 31, 2023

Increasing evidence links the gut microbiota (GM) to Alzheimer's disease (AD) but mechanisms through which bacteria influence brain are still unclear. This study tests hypothesis that GM and mediators of microbiota-gut-brain axis (MGBA) associated with amyloid cascade in sporadic AD.

Язык: Английский

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Metabolic reprogramming in inflammatory microglia indicates a potential way of targeting inflammation in Alzheimer's disease

Redox Biology, Год журнала: 2023, Номер 66, С. 102846 - 102846

Опубликована: Авг. 9, 2023

Microglia activation drives the pro-inflammatory activity in early stages of Alzheimer's disease (AD). However, mechanistic basis is elusive, and hypothesis targeting microglia to prevent AD onset little explored. Here, we demonstrated that upon LPS exposure, shift towards an energetic phenotype characterised by high glycolysis mitochondrial respiration with dysfunction. Although electron transport chain (ETC) complexes boosted LPS, this mostly devoted generation reactive oxygen species. We showed inhibiting succinate dehydrogenase (SDH) dimethyl malonate (DMM), it possible modulate LPS-induced metabolic rewiring, facilitating anti-inflammatory phenotype. DMM improves function a direct way reducing biogenesis. Moreover, block SDH inhibits recruitment hypoxia inducible-factor 1 α (HIF-1α), which mediates induction cytokine expression. Similar bioenergetic alterations were observed isolated from mice (3xTg-AD), present levels circulating brain toll-like receptor4 (TLR4). well-established model was used show potential effect inhibition vivo as administration abrogated inflammation modulated 3xTg-AD mice. The RNA-sequencing analysis public dataset confirmed consistent transcription genes encoding for ETC subunits (5xFAD). In conclusion, TLR4 promotes changes microglia, might represent promising therapeutic target development.

Язык: Английский

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Gut microbiome-targeted therapies for Alzheimer’s disease

Gut Microbes, Год журнала: 2023, Номер 15(2)

Опубликована: Ноя. 7, 2023

The advent of high­throughput ‘omics’ technologies has improved our knowledge gut microbiome in human health and disease, including Alzheimer’s disease (AD), a neurodegenerative disorder. Frequent bidirectional communications mutual regulation exist between the gastrointestinal tract central nervous system through gut-brain axis. A large body research reported close association microbiota AD development, restoring healthy may curb or even improve symptoms progression. Thus, modulation become novel paradigm for clinical management AD, emerging effort focused on developing potential strategies preventing and/or treating disease. In this review, we provide an overview connection causal relationship dysbiosis mechanisms driving progression, successes challenges implementing available microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, fecal transplantation) preventive therapeutic preclinical intervention studies AD. Finally, discuss future directions field.

Язык: Английский

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Hormetic Nutrition and Redox Regulation in Gut–Brain Axis Disorders

Antioxidants, Год журнала: 2024, Номер 13(4), С. 484 - 484

Опубликована: Апрель 18, 2024

The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience overall human health have received much attention. Recently, the gut-brain axis has attracted prominent interest preventing therapeutically impacting neuropathologies gastrointestinal diseases. Polyphenols polyphenol-combined nanoparticles in synergy with probiotics shown to improve gut bioavailability blood-brain barrier (BBB) permeability, thus inhibiting oxidative stress, metabolic dysfunction inflammation linked dysbiosis ultimately onset progression central nervous system (CNS) disorders. In accordance hormesis, polyphenols display biphasic dose-response by activating at a low dose Nrf2 pathway resulting upregulation

Язык: Английский

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Feeding gut microbes to nourish the brain: unravelling the diet–microbiota–gut–brain axis

Nature Metabolism, Год журнала: 2024, Номер 6(8), С. 1454 - 1478

Опубликована: Авг. 22, 2024

Язык: Английский

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