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The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome

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Abstract

Introduction

The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota.

Objectives

Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites.

Methods

A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput 1H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9 ± 1.8 SE years old) and twenty-five non-ME/CFS female (33.0 ± 1.6 SE years old).

Results

The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA. In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients.

Conclusion

Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism.

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Abbreviations

BCFA:

Branched-chain fatty acids

IBD:

Irritable bowel disease

ME/CFS:

Myalgic encephalomyelitis/chronic fatigue syndrome

NOESY:

Nuclear overhauser effect spectroscopy

NMR:

Nuclear magnetic resonance

PCA:

Principal component analysis

SCFA:

Short chain fatty acids

TOCSY:

Total correlated spectroscopy

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Acknowledgements

The authors of this work would like to thank the nursing and administrative staff at the CFS Discovery clinic for their important help throughout this study.

Funding

This work was supported by Grants from the Judith Jane Mason and Harold Stannett Williams Memorial Foundation (The Mason Foundation) CT9957 and MAS2015F020 and equipment Grants from the Rowden White foundation and State of Victoria.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, VIC, 3010, Australia

    Christopher W. Armstrong & Paul R. Gooley

  2. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, 3010, Australia

    Neil R. McGregor

  3. CFS Discovery, Donvale Medical Centre, Donvale, VIC, 3111, Australia

    Donald P. Lewis

  4. Bioscreen (Aust) Pty Ltd, 5 Little Hyde St., Yarraville, VIC, 3013, Australia

    Henry L. Butt

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  1. Christopher W. Armstrong
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  2. Neil R. McGregor
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  3. Donald P. Lewis
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  4. Henry L. Butt
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  5. Paul R. Gooley
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Corresponding author

Correspondence to Paul R. Gooley.

Ethics declarations

This study was approved by the University of Melbourne human research ethics committee (HREC #0723086).

Conflict of interest

There were no conflicts of interest.

Additional information

Data deposition The data for this study has been deposited at MetaboLights (http://www.ebi.ac.uk/metabolights) with Accession No. MTBLS369.

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Armstrong, C.W., McGregor, N.R., Lewis, D.P. et al. The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome. Metabolomics 13, 8 (2017). https://doi.org/10.1007/s11306-016-1145-z

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