From Molecular Biosystems, 23 December 2016.
Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism
Arnaud Germain(a), David Ruppert(b), Susan M. Levine(a) and Maureen R. Hanson(*,a)
a) Department of Molecular Biology and Genetics, Cornell University, Ithaca, USA
b) Department of Statistical Science and School of Operations Research and Information Engineering, Cornell University, Ithaca, USA
* Correspondence email: firstname.lastname@example.org
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS.
Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established.
In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins.
This approach to examine the complex array of symptoms and underlying foundation of ME/CFS revealed 74 differentially accumulating metabolites, out of 361 (P<0.05), and 35 significantly altered after statistical correction (Q<0.15). The latter list includes several essential energy-related compounds which could theoretically be linked to the general lack of energy observed in ME/CFS patients. Pathway analysis points to a few pathways with high impact and therefore potential disturbances in patients, mainly taurine metabolism and glycerophospholipid metabolism, combined with primary bile acid metabolism, as well as glyoxylate and dicarboxylate metabolism and a few other pathways, all involved broadly in fatty acid metabolism. Purines, including ADP and ATP, pyrimidines and several amino acid metabolic pathways were found to be significantly disturbed. Finally, glucose and oxaloacetate were two main metabolites affected that have a major effect on sugar and energy levels. Our work provides a prospective path for diagnosis and understanding of underlying mechanisms of ME/CFS.
From Metabolomics, January 2017.
The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome
Christopher W. Armstrong(1), Neil R. McGregorDonald(2), P. Lewis(3), Henry L. Butt(4). Paul R Gooley (1).
1) Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute University of Melbourne, Parkville, Australia
2) Faculty of Medicine, Dentistry and Health Sciences University of Melbourne Parkville. Australia
3) CFS Discovery, Donvale Medical Centre, Donvale, Australia
4) Bioscreen (Aust) Pty Ltd, Yarraville. Australia
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.
From the Journal of Medicine and Therapeutics (new open access journal), 9 December 2016.
Estimating the disease burden of ME/CFS in the United States and its relation to research funding
Mary. E. Dimmock
Independent Researcher, Connecticut, USA
Arthur A. Mirin
Applied Mathematician, California, USA
Leonard A. Jason
Professor of Psychology, Director, Center for Community Research DePaul University, 990 W. Fullerton Ave, Suite 3100, Chicago, Il. 60614, USA, Tel: 773-325-2018.
At the National Institutes of Health (NIH), burden of disease is an important factor in funding decisions along with such factors as scientific opportunity, the quality of the science, and the interest of researchers.
Recent studies have quantified the burden for a number of diseases in the United States and the NIH has used that information to analyze how its own funding patterns correspond to disease burden. However, the burden of disease has not been quantified for myalgic encephalomyelitis, also called chronic fatigue syndrome (ME/CFS) and is often underestimated due to a lack of research and the misperceptions about the nature of the disease.
Using the limited information in the literature, this paper develops a preliminary estimate of the disease burden of ME/CFS in the United States, using the World Health Organization’s Disability Adjusted Life Years (DALY) measure. The ME/CFS DALY estimate is then compared to the NIH’s 2013 analysis of research funding versus DALY across other funded diseases in order to estimate a level of funding for ME/CFS that would be commensurate with disease burden.
Even given the limitations arising from sparse data, this analysis demonstrates that federal research funding for this disease is far less than what would be expected by the burden of the disease.
We conclude that the annual research funding for ME/CFS would need to increase twenty-five fold or more to be commensurate with disease burden. This level of funding would best leverage the growing interest of researchers and the significant scientific opportunities that exist to understand the pathology of this disease and to advance diagnostics and treatments.