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The Relationship Between the Gut Microbiome and Neurodegenerative Diseases.

ABSTRACT: Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

SUBMITTER: Zhu X

PROVIDER: S-EPMC8490573 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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The Relationship Between the Gut Microbiome and Neurodegenerative Diseases.

Zhu Xueling X Li Bo B Lou Pengcheng P Dai Tingting T Chen Yang Y Zhuge Aoxiang A Yuan Yin Y Li Lanjuan L

Neuroscience bulletin 20210703 10

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of i ...[more]

PMID: 34216356

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Project description:Background: Neurodegenerative diseases (NDDs) are the leading cause of disability worldwide while their metabolic pathogenesis is unclear. Genome-wide association studies (GWASs) offer an unprecedented opportunity to untangle the relationship between metabolites and NDDs. Methods: By leveraging two-sample Mendelian randomization (MR) approaches and relying on GWASs summary statistics, we here explore the causal association between 486 metabolites and five NDDs including Alzheimer's Disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson's disease (PD), and multiple sclerosis (MS). We validated our MR results with extensive sensitive analyses including MR-PRESSO and MR-Egger regression. We also performed linkage disequilibrium score regression (LDSC) and colocalization analyses to distinguish causal metabolite-NDD associations from genetic correlation and LD confounding of shared causal genetic variants. Finally, a metabolic pathway analysis was further conducted to identify potential metabolite pathways. Results: We detected 164 metabolites which were suggestively associated with the risk of NDDs. Particularly, 2-methoxyacetaminophen sulfate substantially affected ALS (OR = 0.971, 95%CIs: 0.961 ∼ 0.982, FDR = 1.04E-4) and FTD (OR = 0.924, 95%CIs: 0.885 ∼ 0.964, FDR = 0.048), and X-11529 (OR = 1.604, 95%CIs: 1.250 ∼ 2.059, FDR = 0.048) and X-13429 (OR = 2.284, 95%CIs: 1.457 ∼ 3.581, FDR = 0.048) significantly impacted FTD. These associations were further confirmed by the weighted median and maximum likelihood methods, with MR-PRESSO and the MR-Egger regression removing the possibility of pleiotropy. We also observed that ALS or FTD can alter the metabolite levels, including ALS and FTD on 2-methoxyacetaminophen sulfate. The LDSC and colocalization analyses showed that none of the identified associations could be driven by genetic correlation or confounding by LD with common causal loci. Multiple metabolic pathways were found to be involved in NDDs, such as "urea cycle" (P = 0.036), "arginine biosynthesis" (P = 0.004) on AD and "phenylalanine, tyrosine and tryptophan biosynthesis" (P = 0.046) on ALS. Conclusion: our study reveals robust bidirectional causal associations between servaral metabolites and neurodegenerative diseases, and provides a novel insight into metabolic mechanism for pathogenesis and therapeutic strategies of these diseases.

Project description:Primates have evolved a variety of feeding habits and intestinal physiological structure. Gut microbiome act as metabolic organs in many biological processes and play a vital role in adaptation to dietary niches. Gut microbiome also convert primary bile acids (BAs) to secondary. BAs profile and gut microbiome are together influenced by diets and play a significant role in nutrient absorption. The regulation between gut microbiome and BAs metabolism is bidirectional although the relationship in primates consuming diverse diets is still unclear. Here, we investigated gut microbiome structures, fecal BAs profile, and their relationship in primates preferring three distinct diets. We found that gut microbiome communities are well differentiated among dietary groups. Folivorous primates had higher Firmicutes abundance and lower Prevotella to Bacaeroides ratios, possibly related to fiber consumption. Frugivorous primates are colonized predominantly by Prevotella and Bacteroides, pointing to an increased adaptation to high-sugar and simple carbohydrate diets. Likewise, BA profiles differ according to diet in a manner predictable from the known effects of BAs on metabolism. Folivorous primates have high conjugated bile acid levels and low unconjugated to conjugated BA ratios, consistent with their fiber-rich leaf-eating diet. Much of the differentiation in secondary and unconjugated BAs is associated with microbiome composition shifts and individual bile acid concentrations are correlated with the abundance of distinct bacterial taxonomic groups. Omnivores have higher concentrations of secondary BAs, mainly lithocholic acid (LCA). These levels are significantly positively correlated with the presence of Clostrida species, showing that the digestion requirements of omnivores are different from plant-eating primates. In conclusion, gut microbiome and BAs can respond to changes in diet and are associated with nutrient component consumption in each diet primate group. Our study is the first to demonstrate BA profile differentiation among primates preferring diverse diets. BAs thus appear to work with gut microbiome to help primates adapt to their diet.

Dataset Information

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases.

Publications

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases.

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