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Review
. 2022 Sep 30:2022:3300903.
doi: 10.1155/2022/3300903. eCollection 2022.

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Mahendra P Singh  1 , Riya Chakrabarty  1 , Shabnam Shabir  1 , Sumaira Yousuf  1 , Ahmad A Obaid  2 , Mahmoud Moustafa  3   4 , Mohammed Al-Shehri  3 , Ahmed Al-Emam  5   6 , Abdulhakeem S Alamri  7   8 , Walaa F Alsanie  7   8 , Majid Alhomrani  7   8 , Anastasiia D Shkodina  9 , Sandeep K Singh  10
Affiliations
Review

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Mahendra P Singh et al. Mediators Inflamm. .

Abstract

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
An illustration of microbiome-gut-brain axis in Parkinson's condition. The blood-brain barrier (BBB) may be permeable to lipopolysaccharide (LPS) and other bacterial metabolites, which could allow them to enter the brain and cause the release of several chemokines and cytokines that would contribute to inflammation in Parkinson's disease. Leaky gut also known as compromised gut epithelial barrier integrity may result from microorganisms in the lumen of the gut promoting inflammatory mechanisms and harming intestinal enterocytes. Bacterial metabolites, like LPS, can cross the compromised gut barrier from the lumen of the gut to the bloodstream and potentially cause systemic and neuroinflammation in the brain.
Figure 2
Figure 2
Crosstalk between the gut microbiome and the brain in Alzheimer's disease. Metabolic, endocrine, neurological, and immunological communication routes exist between the gut microbiota and the brain, and they can act independently or collaboratively.
Figure 3
Figure 3
Possible mechanisms responsible for the effect of the digestive tract microbiome on the pathogenesis of ALS. Microbial metabolic end products may indirectly influence the central nervous system (CNS) through immune system modulation. Toxins and neuroactive metabolites produced by a damaged intestinal epithelial barrier or enteric bacteria can overcome the blood-brain barrier, diffuse to the systemic circulation, and impact on ALS pathogenesis. Metabolites produced by bacteria can alter energy homeostasis, encourage oxidative stress, and cause mitochondrial dysfunction and neuroinflammation.
Figure 4
Figure 4
Role of Escherichia coli (E. coli): Some various ways and genes contribute to the generation of NO within the body of an organism. Among them, E. coli serves as a potent medium. Researchers have revealed that E. coli is significantly capable of converting nitrites into nitric oxides in a neutral pH environment.
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References

    1. Fraher M., O’Toole P., Quigley E. Techniques used to characterize the gut microbiota: a guide for the clinician. Nature Reviews Gastroenterology and Hepatology . 2012;9(6):312–322. doi: 10.1038/nrgastro.2012.44. - DOI - PubMed
    1. Tse J. K. Gut Microbiota, Nitric oxide, and microglia as prerequisites for neurodegenerative disorders. ACS Chemical Neuroscience . 2017;8(7):1438–1447. doi: 10.1021/acschemneuro.7b00176. - DOI - PubMed
    1. Desbonnet L., Clarke G., Traplin A., et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behavior. Brain, Behavior, and Immunity . 2015;48:165–173. doi: 10.1016/j.bbi.2015.04.004. - DOI - PubMed
    1. Rao M., Gershon M. The bowel and beyond: the enteric nervous system in neurological disorders. Nature Reviews Gastroenterology & Hepatology . 2016;13(9):517–528. doi: 10.1038/nrgastro.2016.107. - DOI - PMC - PubMed
    1. Hill J. M., Bhattacharjee S., Pogue A. I., Lukiw W. J. The gastrointestinal tract microbiome and potential link to Alzheimer’s disease. Frontiers in Neurology . 2014;5(5) doi: 10.3389/fneur.2014.00043. - DOI - PMC - PubMed