Dataset Information

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome.

ABSTRACT: Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. This work reports that MG is characterized by decreased ?-phylogenetic diversity, and significantly disturbed gut microbiome and fecal metabolome. The altered gut microbial composition is associated with fecal metabolome changes, with 38.75% of altered bacterial operational taxonomic units showing significant correlations with a range of metabolite biomarkers. Some microbes are particularly linked with MG severity. Moreover, a combination of microbial makers and their correlated metabolites enable discriminating MG from healthy controls (HCs) with 100% accuracy. To investigate whether disturbed gut mcirobiome might contribute to the onset of MG, germ-free (GF) mice are initially colonized with MG microbiota (MMb) or healthy microbiota (HMb), and then immunized in a classic mouse model of MG. The MMb mice demonstrate substantially impaired locomotion ability compared with the HMb mice. This effect could be reversed by cocolonizing GF mice with both MMb and HMb. The MMb mice also exhibit similar disturbances of fecal metabolic pathways as found in MG. Together these data demonstrate disturbances in microbiome composition and activity that are likely to be relevant to the pathogenesis of MG.

SUBMITTER: Zheng P

PROVIDER: S-EPMC6755540 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome.

Zheng Peng P Li Yifan Y Wu Jing J Zhang Hanping H Huang Yu Y Tan Xunmin X Pan Junxi J Duan Jiajia J Liang Weiwei W Yin Bangmin B Deng Fengli F Perry Seth W SW Wong Ma-Li ML Licinio Julio J Wei Hong H Yu Gang G Xie Peng P

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20190731 18

Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. This work reports that MG is characterized by decreased α-phylogenetic diversity, and significantly disturbed gut microbiome and fecal metabolome. The altered gut microbial composition is associated with fecal metabolome changes, with 38.75% of altered bacterial operational taxonomic units showing significant correlati ...[more]

PMID: 31559142

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Project description:BackgroundChronic kidney disease (CKD) is a severe public health problem associated with a disordered gut microbiome. However, the functional alterations of microbiota and their cross talk with metabolism pathways based on disease severity remain unclear.ResultsWe performed metagenomics and untargeted metabolomics in a cohort of 68 patients with CKD of differing severities and 20 healthy controls to characterize the complex interplay between the gut microbiome and fecal and serum metabolites during CKD progression. We identified 26 microbial species that significantly changed in patients with CKD; 18 species changed as the disease progressed, and eight species changed only in a specific CKD group. These distinct changes in gut microbiota were accompanied by functional alterations in arginine and proline, arachidonic acid, and glutathione metabolism and ubiquinone and other terpenoid-quinone biosynthesis pathways during CKD progression. Further metabolomic analyses revealed that the distributions of toxic and pro-oxidant metabolites from these four essential metabolic pathways varied in the feces and serum as CKD progressed. Furthermore, we observed a complex co-occurrence between CKD severity-related bacteria and the characterized metabolites from the four essential metabolic pathways. Notably, Ruminococcus bromii, fecal hydroquinone, and serum creatinine were identified as the main contributors to the integrated network, indicating their key roles in CKD progression. Moreover, a noninvasive model including R. bromii and fecal hydroquinone, L-cystine, and 12-keto-tetrahydro-LTB4 levels classified the CKD severity (area under the curve [AUC]: > 0.9) and had better performance than the serum creatinine level for mild CKD (AUC: 0.972 vs. 0.896).ConclusionsPerturbed CKD severity-related gut microbiota may contribute to unbalanced toxic and pro-oxidant metabolism in the gut and host, accelerating CKD progression, which may be an early diagnostic and therapeutic target for CKD. Video Abstract.

Dataset Information

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome.

Publications

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome.

Similar Datasets

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