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Multi-omics analyses of serum metabolome and gut microbiome reveal shifted metabolites associated with gut microbial dysbiosis in Guillain-Barre syndrome

ABSTRACT:

Objective: Guillain barre syndrome (GBS) is a rare immune-mediated inflammatory disease of the complex peripheral nervous system. Long-term “silent infection” caused by changes in intestinal flora is potentially a contributing factor for immune-mediated inflammatory diseases, but the causative link between GBS and intestinal flora remains unclear. The present study aimed to characterize gut microbiome structure and estimate its association with the serum metabolic profile and in GBS.

Methods: Untargeted metabolomics profiling of serum, using liquid chromatography-mass spectrometry, and metagenomics sequencing of stool samples from a cohort of GBS and non-GBS subjects were performed to evaluate serum metabolic profiles and gut microbiome structure in GBS subjects relative to healthy controls. Pearson’s correlation analysis was used to estimate the correlations between the gut microbial abundance and serum metabolic profile.

Results: For intestinal microflora, Ligilactobacillus_salivarius, Klebsiella pneumonia, Enterocloster bolteae and Methanobrevibacter smithii were notably more abundant in GBS subjects, while Bacteroides sp., Roseburia hominis, and Paraprevotella xylaniphila decreased significantly. Metabolome data revealed that the gamma-aminobutyric acid (GABA) and secondary cholic acid metabolism were perturbed in GBS. GABA increased significantly, while secondary cholic acids as methyl deoxycholate, glycodeoxycholic acid, glycolithocholic acid, taurolithocholic acid and coprocholic acid, decreased significantly in GBS versus non-GBS controls. Metagenome data also revealed that GABA biosynthesis pathway was enriched, while secondary cholic acid metabolism pathways were decreased in gut microbes in GBS subjects. Correlation analysis revealed that changes in GABA were associated with altered gut microbes, such as Enterococcus species, Ligilactobacillus salivarius, Enterocloster bolteae and Methanobrevibacter smithii, and changes in secondary cholic acids were positively correlated with Bacteroides species and Roseburia species.

Conclusion: The well-known opportunistic pathogenic Klebsiella pneumonia and other special gut microbes significantly enriched in GBS. GABA and secondary cholic acid metabolism were significantly disturbed in GBS subjects and might be affected by the dysbiosis of gut microbial flora. These findings suggest that GABA may be a promising biomarker for the diagnosis of GBS and that modulation of gut microbiota might impact the clinical course of GBS.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS10392 | MetaboLights | 2025-02-20

REPOSITORIES: MetaboLights

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			Action	DRS
	2.1.DataPreprocessed.xlsx	Xlsx
	21P23410095_BEHC18_NEG.raw	Raw
	21P23410096_BEHC18_NEG.raw	Raw
	21P23410097_BEHC18_NEG.raw	Raw
	21P23410098_BEHC18_NEG.raw	Raw

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Multi-omics analyses of serum metabolome and gut microbiome reveal shifted metabolites associated with gut microbial dysbiosis in Guillain-Barre syndrome

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