Microbiota‐Host Immunity Communication in Neurodegenerative Disorders: Bioengineering Challenges for In Vitro Modeling

Boeri, Lucia; Perottoni, Simone; Izzo, Luca; Giordano, Carmen; Albani, Diego

doi:10.1002/adhm.202002043

Cited by 21 publications

(15 citation statements)

References 208 publications

(218 reference statements)

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“…Consequently, neuroinflammation and cognitive impairment may appear as subsequent factors to oral dysbiosis based on the assumptions reported in these studies. Furthermore, oral pathogens such as P. gingivalis lead to an ‘oralization’ of the intestinal microbiota [ 134 , 140 ], a mechanism that produces intestinal inflammation, and may be linked to apparition and sustainment of neuroinflammation [ 128 , 141 ] through translocation of oral/intestinal toxic bacterial proteases to the brain [ 136 ]. Classical inflammatory mediators, such as eicosanoids and cytokines, may also contribute to neurodegeneration as detailed.…”

Section: Resultsmentioning

confidence: 99%

Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review

et al. 2022

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Imbalances of the oral microbiota and dysbiosis have traditionally been linked to the occurrence of teeth and oral diseases. However, recent findings indicate that this microbiota exerts relevant influence in systemic health. Dysbiosis of the oral microbiota is implicated in the apparition and progression of cardiovascular, neurodegenerative and other major human diseases. In fact, the oral microbiota are the second most diverse and largely populated microbiota of the human body and its relationships with systemic health, although widely explored, they still lack of proper integration. The purpose of this systematic review is thus to widely examine the implications of oral microbiota in oral, cardiovascular and neurodegenerative diseases to offer integrative and up-to-date interpretations. To achieve that aim, we identified a total of 121 studies curated in PUBMED from the time interval January 2003–April 2022, which after careful screening resulted in 79 studies included. The reviewed scientific literature provides plausible vias of implication of dysbiotic oral microbiota in systemic human diseases, and encourages further research to continue elucidating the highly relevant and still poorly understood implications of this niche microbiota in systemic health. PROSPERO Registration Number: CRD42022299692. This systematic review follows relevant PRISMA guidelines.

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Section: Resultsmentioning

confidence: 99%

Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review

et al. 2022

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“…Validation and standardization will assist the choice of model for different questions. Facilitating access to realistic, highperformance systems (Boeri et al, 2021) seems likely to improve diagnostics, clinical applications, and understanding of different pathologies.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Study of BBB Dysregulation in Neuropathogenicity Using Integrative Human Model of Blood–Brain Barrier

Gama

Morin‐Brureau

2022

Front. Cell. Neurosci.

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The blood–brain barrier (BBB) is a cellular and physical barrier with a crucial role in homeostasis of the brain extracellular environment. It controls the imports of nutrients to the brain and exports toxins and pathogens. Dysregulation of the blood–brain barrier increases permeability and contributes to pathologies, including Alzheimer's disease, epilepsy, and ischemia. It remains unclear how a dysregulated BBB contributes to these different syndromes. Initial studies on the role of the BBB in neurological disorders and also techniques to permit the entry of therapeutic molecules were made in animals. This review examines progress in the use of human models of the BBB, more relevant to human neurological disorders. In recent years, the functionality and complexity of in vitro BBB models have increased. Initial efforts consisted of static transwell cultures of brain endothelial cells. Human cell models based on microfluidics or organoids derived from human-derived induced pluripotent stem cells have become more realistic and perform better. We consider the architecture of different model generations as well as the cell types used in their fabrication. Finally, we discuss optimal models to study neurodegenerative diseases, brain glioma, epilepsies, transmigration of peripheral immune cells, and brain entry of neurotrophic viruses and metastatic cancer cells.

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“…In addition, there are other oral microbial infections that also play a key role in the development of PD lesions. For instance, the microbiota of patients with PD has been found to contain less Firmicutes (such as Faecalibacterium, Clostridium, and Blautia) and more Bacteroidetes (Bacteroides and Prevotella) than healthy controls ( Boeri et al, 2021 ). The study aimed to investigate the association between neurodegenerative disorders and periodontitis.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of gene expression profile and functional analysis in periodontitis and Parkinson’s disease

Shi

et al. 2022

Front. Aging Neurosci.

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Periodontitis is a chronic inflammatory disease inextricably linked to both the innate and acquired immune systems of the body. Parkinson’s disease (PD) is a neurodegenerative disease caused by immune system dysfunction. Although recent studies suggest that a clinical relationship exists between PD and periodontitis, the pathogenesis of this relationship is unclear. Therefore, in the present study, we obtained datasets of periodontitis and PD from the Gene Expression Omnibus (GEO) database and extracted 785 differentially expressed genes (DEGs), including 15 common upregulated genes and four common downregulated genes. We performed enrichment analyses of these DEGs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. We found that the genes were mainly enriched in keratinocyte differentiation, neuronal cell bodies, and structural constituents of epidermis terms, and pathways such as immune response and synaptic pathways. In addition, we screened matching hub genes by constructing a protein–protein interaction (PPI) network map and a Molecular Complex Detection (MCODE) map using the Cytoscape software. The hub genes were then subjected to GO enrichment analysis, which revealed that the dopamine biosynthetic process, dopaminergic synapse and dopamine-binding terms, and dopaminergic synapse and serotonergic synapse pathways were primarily where they were expressed. Finally, we selected four of these genes for validation in the periodontitis and PD datasets, and we confirmed that these hub genes were highly sensitive and specific for diagnosing and monitoring PD and periodontitis. In conclusion, the above experimental results indicate that periodontitis is a high-risk factor for PD, and the association between these two conditions is mainly manifested in immune and dopamine-related pathways. Hub genes, such as the CDSN, TH, DDC, and SLC6A3 genes, may serve as potential biomarkers for diagnosing or detecting PD.

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Microbiota‐Host Immunity Communication in Neurodegenerative Disorders: Bioengineering Challenges for In Vitro Modeling

Cited by 21 publications

References 208 publications

Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review

Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review

Study of BBB Dysregulation in Neuropathogenicity Using Integrative Human Model of Blood–Brain Barrier

Bioinformatics analysis of gene expression profile and functional analysis in periodontitis and Parkinson’s disease

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