Gut Microbiota and Immune System Dynamics in Parkinson's and Alzheimer's Diseases

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Nov 27

PMID 39596232

Authors

Natasa Kustrimovic

Sahar Balkhi

Giorgia Bilato

Lorenzo Mortara

Affiliations

Soon will be listed here.

Abstract

The gut microbiota, a diverse collection of microorganisms in the gastrointestinal tract, plays a critical role in regulating metabolic, immune, and cognitive functions. Disruptions in the composition of these microbial communities, termed dysbiosis, have been linked to various neurodegenerative diseases (NDs), such as Parkinson's disease (PD) and Alzheimer's disease (AD). One of the key pathological features of NDs is neuroinflammation, which involves the activation of microglia and peripheral immune cells. The gut microbiota modulates immune responses through the production of metabolites and interactions with immune cells, influencing the inflammatory processes within the central nervous system. This review explores the impact of gut dysbiosis on neuroinflammation, focusing on the roles of microglia, immune cells, and potential therapeutic strategies targeting the gut microbiota to alleviate neuroinflammatory processes in NDs.

Citing Articles

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References

Dutta G, Zhang P, Liu B . The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and drug discovery. Fundam Clin Pharmacol. 2008; 22(5):453-64. PMC: 2632601. DOI: 10.1111/j.1472-8206.2008.00616.x. View

Sittipo P, Choi J, Lee S, Lee Y . The function of gut microbiota in immune-related neurological disorders: a review. J Neuroinflammation. 2022; 19(1):154. PMC: 9199126. DOI: 10.1186/s12974-022-02510-1. View

Nagpal R, Neth B, Wang S, Craft S, Yadav H . Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019; 47:529-542. PMC: 6796564. DOI: 10.1016/j.ebiom.2019.08.032. View

Malm T, Koistinaho M, Muona A, Magga J, Koistinaho J . The role and therapeutic potential of monocytic cells in Alzheimer's disease. Glia. 2010; 58(8):889-900. DOI: 10.1002/glia.20973. View

Jucker M, Walker L . Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases. Nat Neurosci. 2018; 21(10):1341-1349. PMC: 6375686. DOI: 10.1038/s41593-018-0238-6. View

Dugger B, Dickson D . Pathology of Neurodegenerative Diseases. Cold Spring Harb Perspect Biol. 2017; 9(7). PMC: 5495060. DOI: 10.1101/cshperspect.a028035. View

Agus A, Planchais J, Sokol H . Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018; 23(6):716-724. DOI: 10.1016/j.chom.2018.05.003. View

Lu R, Zhang L, Yang X . Interaction between autophagy and the NLRP3 inflammasome in Alzheimer's and Parkinson's disease. Front Aging Neurosci. 2022; 14:1018848. PMC: 9574200. DOI: 10.3389/fnagi.2022.1018848. View

Barcia C, Ros C, Annese V, Gomez A, Ros-Bernal F, Aguado-Llera D . IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson's disease. Cell Death Dis. 2012; 3:e379. PMC: 3434670. DOI: 10.1038/cddis.2012.123. View

10.

Fox S . Non-dopaminergic treatments for motor control in Parkinson's disease. Drugs. 2013; 73(13):1405-15. DOI: 10.1007/s40265-013-0105-4. View

11.

Parashar A, Udayabanu M . Gut microbiota: Implications in Parkinson's disease. Parkinsonism Relat Disord. 2017; 38:1-7. PMC: 7108450. DOI: 10.1016/j.parkreldis.2017.02.002. View

12.

Mousavinasab F, Karimi R, Taheri S, Ahmadvand F, Sanaaee S, Najafi S . Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering. Cancer Cell Int. 2023; 23(1):271. PMC: 10640760. DOI: 10.1186/s12935-023-03095-2. View

13.

Kim C, Ho D, Suk J, You S, Michael S, Kang J . Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun. 2013; 4:1562. PMC: 4089961. DOI: 10.1038/ncomms2534. View

14.

Connolly B, Lang A . Pharmacological treatment of Parkinson disease: a review. JAMA. 2014; 311(16):1670-83. DOI: 10.1001/jama.2014.3654. View

15.

Kustrimovic N, Rasini E, Legnaro M, Bombelli R, Aleksic I, Blandini F . Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson's Disease. Sci Rep. 2016; 6:33738. PMC: 5031979. DOI: 10.1038/srep33738. View

16.

Dinan T, Cryan J . The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol Clin North Am. 2017; 46(1):77-89. DOI: 10.1016/j.gtc.2016.09.007. View

17.

Mayer E, Nance K, Chen S . The Gut-Brain Axis. Annu Rev Med. 2021; 73:439-453. DOI: 10.1146/annurev-med-042320-014032. View

18.

Ghaisas S, Maher J, Kanthasamy A . Gut microbiome in health and disease: Linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacol Ther. 2015; 158:52-62. PMC: 4747781. DOI: 10.1016/j.pharmthera.2015.11.012. View

19.

Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi S . Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019; 8(3). PMC: 6463098. DOI: 10.3390/foods8030092. View

20.

Weiss G, Hennet T . Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci. 2017; 74(16):2959-2977. PMC: 11107543. DOI: 10.1007/s00018-017-2509-x. View