The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome
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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.
Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites.
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).
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.
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.
KeywordsMyalgic encephalomyelitis/chronic fatigue syndrome Feces Microbiota Short chain fatty acids Energy metabolism Amino acids
Branched-chain fatty acids
Irritable bowel disease
Myalgic encephalomyelitis/chronic fatigue syndrome
Nuclear overhauser effect spectroscopy
Nuclear magnetic resonance
Principal component analysis
Short chain fatty acids
Total correlated spectroscopy
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.
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.
Compliance with ethical standards
This study was approved by the University of Melbourne human research ethics committee (HREC #0723086).
Conflict of interest
There were no conflicts of interest.
- Armstrong, C. W., McGregor, N. R., Sheedy, J. R., Buttfield, I., Butt, H. L., & Gooley, P. R. (2012). NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome. Clinica Chimica Acta; International Journal of Clinical Chemistry, 413, 1525–1531. doi: 10.1016/j.cca.2012.06.022.CrossRefPubMedGoogle Scholar
- Belenguer, A., Duncan, S. H., Holtrop, G., Anderson, S. E., Lobley, G. E., & Flint, H. J. (2007). Impact of pH on lactate formation and utilization by human fecal microbial communities. Applied and Environmental Microbiology, 73, 6526–6533. doi: 10.1128/AEM.00508-07.CrossRefPubMedPubMedCentralGoogle Scholar
- Borody, T., Leis, S., Campbell, J., Torres, M., & Nowak, A. (2011). Fecal microbiota transplantation (FMT) in multiple sclerosis (MS). American Journal of Gastroenterology, 106, S352–S352.Google Scholar
- Canani, R. B., Costanzo, M. D., Leone, L., Pedata, M., Meli, R., & Calignano, A. (2011). Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World Journal of Gastroenterology: WJG, 17, 1519–1528. doi: 10.3748/wjg.v17.i12.1519.CrossRefPubMedPubMedCentralGoogle Scholar
- den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D. J., & Bakker, B. M. (2013b). The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. Journal of Lipid Research, 54, 2325–2340. doi: 10.1194/jlr.R036012.CrossRefPubMedPubMedCentralGoogle Scholar
- Fremont, M., Coomans, D., Massart, S., & De Meirleir, K. (2013). High-throughput 16 S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients. Anaerobe, 22, 50–56. doi: 10.1016/j.anaerobe.2013.06.002.CrossRefPubMedGoogle Scholar
- Giloteaux, L., Goodrich, J. K., Walters, W. A., Levine, S. M., Ley, R. E., Hanson, M. R. (2016). Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 4, 30 doi: 10.1186/s40168-016-0171-4.CrossRefPubMedPubMedCentralGoogle Scholar
- Rigottier-Gois, L., Rochet, V., Garrec, N., Suau, A., & Dore, J. (2003). Enumeration of Bacteroides species in human faeces by fluorescent in situ hybridisation combined with flow cytometry using 16 S rRNA probes. Systematic and Applied Microbiology, 26, 110–118. doi: 10.1078/072320203322337399.CrossRefPubMedGoogle Scholar
- Sheedy, J. R., et al. (2009). Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo (Athens, Greece), 23, 621–628.Google Scholar
- Tretter, L., & Adam-Vizi, V. (2000). Inhibition of Krebs cycle enzymes by hydrogen peroxide: A key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 20, 8972–8979.Google Scholar
- Walker, A. W., Duncan, S. H., McWilliam Leitch, E. C., Child, M. W., & Flint, H. J. (2005). pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon. Applied and Environmental Microbiology, 71, 3692–3700. doi: 10.1128/AEM.71.7.3692-3700.2005.CrossRefPubMedPubMedCentralGoogle Scholar
- Wang, L., Christophersen, C. T., Sorich, M. J., Gerber, J. P., Angley, M. T., & Conlon, M. A. (2012). Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Digestive Diseases and Sciences, 57, 2096–2102. doi: 10.1007/s10620-012-2167-7.CrossRefPubMedGoogle Scholar
- Willis, A. T. (1991). Anaerobic culture methods. In P. N. Lovett. (Ed.), Anaerobic microbiology a practical approach the practical approach series. (pp. 1–12). New York: IRL Press at Oxford University Press.Google Scholar