Emmanson Emmanson Godswill¹*, Ogunwale Fawas Abiodun², Chiamaka Mercy Ogboji³, Ojo oluwakemi Janet⁴ and Anthonia BO⁵

¹Department of Human Anatomy, University Cross River State, Nigeria
²Department of Human Anatomy, Ekiti State University, Ado-Ekiti, Ekiti State, Nigeria
³Department of Human Anatomy, Ebonyi State University, Nigeria
⁴Department of Human Physiology, Ladoke Akintola University of Technology (LAUTECH), Nigeria
⁵Department of Pharmacy, Universite De Parakou, Nigeria

*Corresponding Author: Emmanson Emmanson Godswill, Department of Human Anatomy, University Cross River State, Nigeria.

Received: March 13, 2024; Published: March 28, 2024

Abstract

Neurodegenerative diseases (NDs) are a group of disorders that cause progressive and irreversible damage to the nervous system, leading to cognitive, motor, and behavioral impairments. NDs, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are major global health challenges, affecting millions of people and imposing significant socioeconomic costs. Despite decades of research, the etiology and pathophysiology of NDs remain poorly understood, and no effective treatments are available to halt or reverse the disease process. Therefore, there is an urgent need to identify novel mechanisms and therapeutic strategies for NDs. In recent years, the gut microbiome, the collective genome of the microorganisms residing in the gastrointestinal tract, has emerged as a key player in the pathogenesis and progression of NDs, providing new insights into potential biomarkers and therapeutic targets. The gut microbiome is a complex and dynamic ecosystem that modulates host physiology, immune function, and metabolism. The gut and the brain communicate bidirectionally through the gut-brain axis (GBA), a multifaceted network that involves neural, hormonal, and immune signaling. The GBA influences neurological health and disease states by regulating various aspects of brain function, such as neurogenesis, synaptic plasticity, neurotransmission, neuroinflammation, and neuroimmunity. Studies have revealed alterations in gut microbiome composition and function in individuals with NDs, indicating a possible causal relationship between gut dysbiosis and disease pathology. For example, in AD, decreased microbial diversity and dysbiosis in specific taxa have been correlated with cognitive impairment and the formation of amyloid-beta plaques in the brain. Likewise, in PD, changes in gut microbiome composition have been associated with motor dysfunction and neuroinflammation, aggravating disease severity. In ALS, dysbiosis in the gut microbial community has been related to disease progression and neuroinflammatory processes. Understanding the role of the gut microbiome in NDs is of paramount importance for several reasons. First, elucidating the molecular mechanisms by which gut microbiome perturbations affect disease pathogenesis may reveal novel therapeutic targets for intervention. Second, identifying microbial biomarkers associated with disease onset and progression could enable early diagnosis and prognosis. Third, modulating the gut microbiome through dietary interventions, probiotics, or fecal microbiota transplantation represents a promising avenue for therapeutic intervention. Despite these advancements, several knowledge gaps and challenges remain. Mechanistic insights into gut microbiome-mediated effects on neurodegeneration are still incomplete, requiring further research. Standardization of methodologies for gut microbiome assessment and translation of research findings into clinical practice are essential for realizing the full potential of microbiome-based interventions in NDs. Therefore, this review aims to comprehensively examine the current understanding of the GBA in AD, PD, and ALS, identify research gaps, and propose future directions for advancing the field.

Keywords: Neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Gut microbiome, Gut-brain axis, Dysbiosis, Cognitive decline, Motor deficits, Neuroinflammation, Therapeutic interventions

References

1. Chandra R., et al. “The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored”. Nature Reviews Neuroscience1 (2023): 1-16.
2. Al Bander HA., et al. “Changes in the composition and function of the gut microbiota and their effects on health and disease”. International Journal of Molecular Sciences24 (2020): 9606.
3. González Olmo MJ and Martínez A. “Influencing elements of human gut microbiota”. Microorganisms2 (2021): 243.
4. Cryan JF and Dinan TG. “Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour”. Nature Reviews Neuroscience 10 (2012): 701-712.
5. Sampson TR and Mazmanian SK. “Control of brain development, function, and behavior by the microbiome”. Cell Host and Microbe 5 (2023): 565-576.
6. Harach T., et al. “Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota”. Scientific Reports 7 (2017): 41802.
7. Bonfili L., et al. “Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels”. Scientific Reports 1 (2017): 1-14.
8. Vogt NM., et al. “Gut microbiome alterations in Alzheimer’s disease”. Scientific Reports1 (2017): 1-11.
9. Sun M., et al. “Altered fecal microbiota correlates with liver biochemistry in nonobese patients with non-alcoholic fatty liver disease”. Scientific Reports1 (2019): 1-10.
10. Hill JM., et al. “The gastrointestinal tract microbiome and potential link to Alzheimer’s disease”. Frontiers in Neurology 5 (2014): 43.
11. Sampson TR., et al. “Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease”. Cell6 (2016): 1469-1480.
12. Bedarf JR., et al. “Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients”. Genome Medicine1 (2017): 1-17.
13. Scheperjans F., et al. “Gut microbiota are related to Parkinson’s disease and clinical phenotype”. Movement Disorders3 (2015): 350-358.
14. Hill-Burns EM., et al. “Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome”. Movement Disorders 5 (2017): 739-749.
15. Wu HJ and Wu E. “The role of gut microbiota in immune homeostasis and autoimmunity”. Gut Microbes 1 (2017): 4-14.
16. Cattaneo A., et al. “Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly”. Neurobiology of Aging 49 (2017): 60-68.
17. Vogt NM., et al. “The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease”. Alzheimer’s Research and Therapy1 (2018): 1-11.
18. Cryan JF and Dinan TG. “Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour”. Nature Reviews Neuroscience10 (2012): 701-712.
19. Sampson TR and Mazmanian SK. “Control of brain development, function, and behavior by the microbiome”. Cell Host and Microbe 5 (2015): 565-576.
20. Harach T., et al. “Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota”. Scientific Reports 7 (2017): 41802.

Citation

Citation: Emmanson Emmanson Godswill., et al. “Investigating the Roles of Gut Microbiome in The Progression of Neurodegenerative Diseases: Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (Als)".Acta Scientific Anatomy 3.4 (2024): 36-48.

Copyright

Copyright: © 2024 Emmanson Emmanson Godswill., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.