Implications of gut and oral microbiota in neuroinflammatory responses in Alzheimer's disease

Bello-Corral, Laura; Alves-Gomes, Lisa; Fernández-Fernández, Jesús Antonio; Fernández-García, Daniel; Casado-Verdejo, Inés; Sánchez-Valdeón, Leticia

doi:10.1016/j.lfs.2023.122132

Cited by 10 publications

(3 citation statements)

References 77 publications

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“…Porphyromonas gingivalis and the gingipains enzyme which it produces have been identified in AD brains. Thus, periodontitis is an anatomically specific infection and risk factor for AD [75,76].…”

Section: Oral Hygiene (Porphyromonas Gingivalis)mentioning

confidence: 99%

Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune–Neuroinflammation Mechanism

Weaver

2023

Brain Sciences

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One of the major obstacles confronting the formulation of a mechanistic understanding for Alzheimer’s disease (AD) is its immense complexity—a complexity that traverses the full structural and phenomenological spectrum, including molecular, macromolecular, cellular, neurological and behavioural processes. This complexity is reflected by the equally complex diversity of risk factors associated with AD. However, more than merely mirroring disease complexity, risk factors also provide fundamental insights into the aetiology and pathogenesis of AD as a neurodegenerative disorder since they are central to disease initiation and subsequent propagation. Based on a systematic literature assessment, this review identified 30 risk factors for AD and then extended the analysis to further identify neuroinflammation as a unifying mechanism present in all 30 risk factors. Although other mechanisms (e.g., vasculopathy, proteopathy) were present in multiple risk factors, dysfunction of the neuroimmune–neuroinflammation axis was uniquely central to all 30 identified risk factors. Though the nature of the neuroinflammatory involvement varied, the activation of microglia and the release of pro-inflammatory cytokines were a common pathway shared by all risk factors. This observation provides further evidence for the importance of immunopathic mechanisms in the aetiopathogenesis of AD.

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Section: Oral Hygiene (Porphyromonas Gingivalis)mentioning

confidence: 99%

Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune–Neuroinflammation Mechanism

Weaver

2023

Brain Sciences

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show abstract

“…Porphyromonas gingivalis and the gingipains enzyme which it produces have been identified in AD brains. Thus, periodontitis is a anatomically specific infection and risk factor for AD [70,71].…”

Section: Oral Hygiene (Porphyromonas Gingivalis)mentioning

confidence: 99%

Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune-Neuroinflammation Mechanism

Weaver

2023

Preprint

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One of the major obstacles confronting the formulation of a mechanistic understanding for Alzheimer’s disease (AD) is its immense complexity – a complexity that traverses the full structural and phenomenological spectrum, including molecular, macromolecular, cellular, neurological and behavioural processes. This complexity is reflected by the equally complex diversity of risk factors associated with AD. However, more than merely mirroring disease complexity, risk factors also provide fundamental insights into the aetiology and pathogenesis of AD as a neurodegenerative disorder since they are central to disease initiation and subsequent propagation. Based on a systematic literature assessment, this review has identified 30 risk factors for AD and then extended the analysis to further identify neuroinflammation as a unifying mechanism present in all 30 risk factors. Although other mechanisms (e.g. vasculopathy) were present in multiple risk factors, dysfunction of the neuroimmune-neuroinflammation axis was uniquely central to all 30 identified risk factors. Though the nature of the neuroinflammatory involvement varied, activation of microglia and the release of pro-inflammatory cytokines was a common pathway shared by all risk factors. This observation provides further evidence for the importance of immunopathic mechanisms in the aetiopathogenesis of AD.

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“…The elucidation of cellular and molecular mechanisms contributing to AD pathogenesis is crucial for identifying new therapeutic targets (Gholami 2023 ). Mechanisms such as oxidative damage and systemic inflammation may accelerate the progression of AD (Chen and Zhong 2014 ; Bello-Corral et al 2023 ). Therapeutic interventions, including anti-inflammatory drugs and antioxidant supplements, have been observed to ameliorate symptoms or slow cognitive decline in AD patients (Fillit et al 1986 ; Ozben and Ozben 2019 ; Collins et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice

Reyes-Reyes,

Brown,

Trial

et al. 2024

Exp Brain Res

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Apolipoprotein E ε4 allele (APOE4) is the predominant genetic risk factor for late-onset Alzheimer’s disease (AD). APOE4 mouse models have provided advances in the understanding of disease pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects like food and bedding can be major sources of changes in rodent microflora. Alterations in intestinal microbial ecology can cause mucosal barrier impairment and increase pro-inflammatory signals. The present study examined the role of sterile and non-sterile food and housing on redox indicators and the immune status of humanized-APOE4 knock-in mice (hAPOe4). hAPOE4 mice were housed under sterile conditions until 22 months of age, followed by the transfer of a cohort of mice to non-sterile housing for 2 months. At 24 months of age, the redox/immunologic status was evaluated by flow cytometry/ELISA. hAPOE4 females housed under non-sterile conditions exhibited: (1) higher neuronal and microglial oxygen radical production and (2) lower CD68+ microglia (brain) and CD8+ T cells (periphery) compared to sterile-housed mice. In contrast, hAPOE4 males in non-sterile housing exhibited: (1) higher MHCII+ microglia and CD11b+CD4+ T cells (brain) and (2) higher CD11b+CD4+ T cells and levels of lipopolysaccharide-binding protein and inflammatory cytokines in the periphery relative to sterile-housed mice. This study demonstrated that sterile vs. non-sterile housing conditions are associated with the activation of redox and immune responses in the brain and periphery in a sex-dependent manner. Therefore, housing status may contribute to variable outcomes in both the brain and periphery.

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Implications of gut and oral microbiota in neuroinflammatory responses in Alzheimer's disease

Cited by 10 publications

References 77 publications

Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune–Neuroinflammation Mechanism

Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune–Neuroinflammation Mechanism

Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune-Neuroinflammation Mechanism

Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice

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