The Role of Microbial Metabolites in the Progression of Neurodegenerative Diseases-Therapeutic Approaches: A Comprehensive Review

Abstract

The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood-brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.

Keywords: fecal microbiota transplantation; gut microbiota; microbial metabolites; neurodegenerative diseases; prebiotics; probiotics; short-chain fatty acids.

Figure 1

The gut microbiota produces metabolites that can exert effects on the CNS through bidirectional communication of the gut–brain axis, leading to neuroinflammation and CNS alterations.

Figure 2

Mechanisms of action of microbial metabolites in neurodegenerative diseases. Microbial metabolites, including butyrate, lipopolysaccharides, neurotransmitters, and tryptophan, affect the progression of neurodegenerative diseases. These metabolites exert an impact on essential signaling pathways within the central nervous system, affecting dopaminergic, cholinergic, and motor neurons. The principal alterations include inflammation, oxidative stress, and mitochondrial dysfunction, which are associated with the pathogenesis of neurodegenerative diseases.

Figure 3

Gut microbiota modulation as therapy for neurodegenerative diseases. The application of various therapeutic interventions based on gut microbiota modification, including probiotics, prebiotics, dietary modifications, antibiotics, and fecal microbiota transplantation, has been observed to influence the production of microbial metabolites. These microbial byproducts have been demonstrated to possess the potential to mitigate intestinal dysbiosis, stimulate the proliferation of bacterial strains with neuroprotective and anti-inflammatory properties, and exert beneficial effects on the symptomatology associated with neurodegenerative diseases.