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Review
. 2023 Feb 19;12(4):1650.
doi: 10.3390/jcm12041650.

Role of Gut Microbiota in Neurological Disorders and Its Therapeutic Significance

Prabhakar Tiwari  1 , Rekha Dwivedi  2 , Manisha Bansal  1 , Manjari Tripathi  2 , Rima Dada  1
Affiliations
Review

Role of Gut Microbiota in Neurological Disorders and Its Therapeutic Significance

Prabhakar Tiwari et al. J Clin Med. .

Abstract

In humans, the gut microbiota (GM) are known to play a significant role in the metabolism of nutrients and drugs, immunomodulation, and pathogen defense by inhabiting the gastrointestinal tract (GIT). The role of the GM in the gut-brain axis (GBA) has been documented for different regulatory mechanisms and associated pathways and it shows different behaviors with individualized bacteria. In addition, the GM are known as susceptibility factor for neurological disorders in the central nervous system (CNS), regulating disease progression and being amenable to intervention. Bidirectional transmission between the brain and the GM occurs in the GBA, implying that it performs a significant role in neurocrine, endocrine, and immune-mediated signaling pathways. The GM regulates multiple neurological disorders by supplementing them with prebiotics, probiotics, postbiotics, synbiotics, fecal transplantations, and/or antibiotics. A well-balanced diet is critically important for establishing healthy GM, which can alter the enteric nervous system (ENS) and regulate multiple neurological disorders. Here, we have discussed the function of the GM in the GBA from the gut to the brain and the brain to the gut, the pathways associated with neurology that interacts with the GM, and the various neurological disorders associated with the GM. Furthermore, we have highlighted the recent advances and future prospects of the GBA, which may require addressing research concerns about GM and associated neurological disorders.

Keywords: gut microbiota; gut–brain axis; neurological disorders; pathogenesis; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Depicts the role of GM in the GBA under microbial balance and imbalance conditions for the pathogenesis of PD. Microbial balance leads to a healthy brain (left side). It includes modifying factors such as beneficial bacteria growth, balanced SCFAs, eubiosis, increased neurotropic factors, the synthesis of anti-oxidant enzymes, anti-inflammatory cytokines, omega-3 fatty acids, polyphenols, and dietary fibers, which in turn keep the brain and biological system healthy, as well as lifestyle changes such as physical exercise, yoga, and meditation, in the intestine of the host. A microbial imbalance leads to the pathogenicity of PD (right side). It occurs due to intestinal dysbiosis, immune dysregulation and inflammation, constipation, decreased short-chain fatty acids (SCFA), the western diet, alcohol, etc. In PD, these factors promote the accumulation of α-synuclein, ROS, and pro-inflammatory cytokines (IL1β, IL6, IL17, and TNF-α), which are transported from the gut to the brain via the vagus nerve.
Figure 2
Figure 2
Demonstrates the role of GM in AD pathogenesis via GBA in both microbial balance and imbalance conditions. A healthy brain (left side) occurs due to a microbial balance condition in the intestine. It is affected by various factors, including the growth of beneficial bacteria, balanced SCFAs, eubiosis, increased neurotropic factors, anti-oxidant enzyme synthesis, anti-inflammatory cytokines, omega-3 fatty acids, polyphenols, dietary fibers, and lifestyle changes such as yoga and meditation;all of these factors contribute to brain health. A pathogen that causes Alzheimer’s disease when there is a microbial imbalance (right side). It may cause intestinal dysbiosis, immune dysregulation and inflammation, constipation (dietary fibers), decreased short-chain fatty acids (SCFA), etc. GM inflammasome proteins cause tau protein hyperphosphorylation and amyloid-load plaque formation in the brain, as well as inflammasome activation, resulting in systemic inflammation, neurodegeneration, cognitive impairment, and brain amyloidosis, thus leading to AD pathogenesis.
Figure 3
Figure 3
Shows an overview of the neurological disorders associated with GM in GBA. This figure illustrates the associated factors that cause the neurological disorder and the pathways involved, which are modulated by factors (negatively modulated) or therapeutics (positively modulated). The dysregulation of these pathways causes several neurological disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), stroke and brain injury, epilepsy, and Huntington’s disease (HD). In addition, we have provided information on microbial treatments that are being utilized to treat neurological disorders, including prebiotics, probiotics, postbiotics, synbiotics, antibiotics, and fecal transplantations. The disease-associated modulation of biomarker levels, as well as the micro-organisms involved in therapeutics and their beneficial effects to prevent the disease, are also represented.
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