Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence

Abstract

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis. As a contributing factor, microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota's diverse microorganisms, and for both neuroimmune and neuroendocrine systems. Here, we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases, with an emphasis on multi-omics studies and the gut virome. The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated. Finally, we discuss the role of diet, prebiotics, probiotics, postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

Keywords: biomarker; diet pattern; gut microbiota; gut-brain axis; metagenomics; mitochondrial dysfunction; multi-omics; neurodegenerative disease; neuroinflammation; probiotic.

Figure 1

Links between the gut microbiota and neurodegenerative diseases. The links between the gut microbiota and neurodegeneration diseases. The hypotha lamopituitary adrenal axis plays an important role in the communication between the brain and the gut microbiota. Neurodegenerative diseases trigger intestinal dysbosis by altering the levels of hormones. Subsequently, intestinal metabolites and inflammatory factors activate microglia mediated by the vagus nerve pathway, ultimately leading to the development of neurodegenerative diseases. Created with BioRender.com. iNOS: Inducible nitric oxide synthase; IL: interleukin; TNF: tumor necrosis factor.

Figure 2

Workflow of the bioinformatics pipeline in metagenomics. Stage 1: Trimmomatic is mainly used to remove low quality reads and adapters from the raw reads. Stage 2: Clean reads are assembled into contigs and then binned. Stage 3: MetaPhIAn4 is mainly employed for taxonomic assignment. Stage 4: Finally, various tools are used for downstream analysis of the data, including phylogeny, diversity analysis, and differential analysis. Created with BioRender.com.

Figure 3

Strategies used to reshape the intestinal microbiota. Prebiotics, mediterranean diet and exercise alleviate the pathological symptoms of neurodegenerative diseases by regulating the gut microbiota, including pathological proteins aggregation, neuroinflammation and hypotha lamopituitary-adrenal axis disorders. Created with BioRender.com. APP: Amyloid-beta precursor protein; Bace: beta-site amyloid-beta precursor protein cleaving enzyme; CORT: corticosterone; CRH: corticotropin releasing hormone; HPA: hypotha lamopituitary-adrenal; IL: interleukin; LRRK2: leucine-rich repeat kinase 2; NE: noradrenaline; TLR: Toll-like receptors; TNF: tumor necrosis factor.