The Gut Microbiome–Brain Crosstalk in Neurodegenerative Diseases

Abstract

The gut–brain axis (GBA) is a complex interactive network linking the gut to the brain. It involves the bidirectional communication between the gastrointestinal and the central nervous system, mediated by endocrinological, immunological, and neural signals. Perturbations of the GBA have been reported in many neurodegenerative diseases, suggesting a possible role in disease pathogenesis, making it a potential therapeutic target. The gut microbiome is a pivotal component of the GBA, and alterations in its composition have been linked to GBA dysfunction and CNS inflammation and degeneration. The gut microbiome might influence the homeostasis of the central nervous system homeostasis through the modulation of the immune system and, more directly, the production of molecules and metabolites. Small clinical and preclinical trials, in which microbial composition was manipulated using dietary changes, fecal microbiome transplantation, and probiotic supplements, have provided promising outcomes. However, results are not always consistent, and large-scale randomized control trials are lacking. Here, we give an overview of how the gut microbiome influences the GBA and could contribute to disease pathogenesis in neurodegenerative diseases.

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

“…[ 27 , 32 , 33 ]. Furthermore, changes in the levels of microorganisms in gut microbiota are associated with neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease [ 34 , 35 ]. The relationship between gut microbiota and various diseases is currently being studied using multi-omics analysis, including metagenomics, metatranscriptomics, metaproteomics, and metabolomics [ 36 ].…”

“…The sequenced DNA is linked using bioinformatics, resulting in the identification of species, strains, and functional genes [ 38 , 39 ]. These metagenomic analyses have revealed the association between changes in the composition of the gut microbiota and neurodegenerative diseases; furthermore, but their means, the association between changes in bacterial species with enzymes that modify BAs and neurodegenerative diseases are also being elucidated [ 34 , 35 ]. In patients with Alzheimer’s disease, Bacteroidetes is positively correlated with Alzheimer’s disease, while Firmicutes and Bifidobacterium are negatively correlated with Alzheimer’s disease [ 40 , 41 , 42 ].…”

“…Furthermore, rat models of Parkinson’s disease induced by rotenone show mitochondrial swelling, and the loss of mitochondrial cristae and UDCA improves these mitochondrial abnormalities [ 134 ]. In addition, several reports have indicated that BSH-containing bacteria, such as Lactobacillus , Bifidobacterium , Enterococcus , and Bacteroides spp., are increased in patients with Parkinson’s disease [ 34 , 35 ]. This indicates a relationship between unconjugated BAs and Parkinson’s disease.…”

Does the Gut Microbial Metabolome Really Matter? The Connection between GUT Metabolome and Neurological Disorders

“…However, according to the state of knowledge, microbiome, and microbiome–metabolome influence on disease progression in these two diseases are the best described so far ( Table 1 ). Interestingly, microbiome and microbiome–metabolome have gained a lot of attention recently [ 141 , 142 ], and new studies shed light on their engagement in multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD) [ 143 ].…”

Gut microbiota, pathogenic proteins and neurodegenerative diseases

“…GM dysregulation is an important factor in the occurrence and development of nervous system diseases (Ghezzi et al, 2022). Therefore, GM targeting is expected to become a new treatment for NDs, with great clinical research prospects.…”