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Adv Sci (Weinh). 2019 Jul 31;6(18):1901441. doi: 10.1002/advs.201901441. eCollection 2019 Sep 18.

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

Zheng P1,2,3, Li Y1,2,3, Wu J4, Zhang H1,2,3, Huang Y1,2,3, Tan X1,2,3, Pan J4, Duan J4, Liang W4, Yin B4, Deng F5, Perry SW6, Wong ML6, Licinio J6, Wei H7, Yu G1, Xie P1,2,3.

Author information

1
Department of Neurology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China.
2
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science Chongqing Medical University Chongqing 400016 China.
3
NHC Key Laboratory of Diagnosis and Treatment on Brain Function and Disease Chongqing 400016 China.
4
The M.O.E. Key Laboratory of Laboratory Medical Diagnostics the College of Laboratory Medicine Chongqing Medical University Chongqing 400016 China.
5
Social Medicine and Health Management Chongqing Medical University Chongqing 400016 China.
6
Department of Psychiatry College of Medicine SUNY Upstate Medical University Syracuse NY 13210 USA.
7
Precision Medicine Institute The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510080 China.

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 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 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.

KEYWORDS:

fecal microbiota transplantation; germ‐free mice; gut microbiome; metabolome; myasthenia gravis

Conflict of interest statement

The authors declare no conflict of interest.

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