A 'characteristic chemical signature' to chronic fatigue syndrome?

Today I'm (belatedly) talking about the paper by Robert Naviaux and colleagues [1] (open-access) and some further peer-reviewed discussion concerning the metabolomics of chronic fatigue syndrome (CFS). Suggesting that "targeted, broad-spectrum metabolomics of plasma not only revealed a characteristic chemical signature but also revealed an unexpected underlying biology" when it comes to CFS, it is not surprising that this work has attracted some media interest (indeed, quite a lot of media interest).

I don't want to regurgitate all the findings given that (a) they are numerous, and (b) the paper is open-access, but there are a few details worth noting.

So:

• Some readers might recognise the names Robert and Jane Naviaux listed as authors on this current paper as one and the same team involved in all that suramin for [mouse] autism work (see here). Their previous focus on the application of metabolomics (specifically the use of mass spectrometry) following the use of suramin hints at the skills and expertise this group have in that field.
• Their research attention was turned to CFS with the aim to put further flesh on the idea that there may be some important biochemistry happening in cases of the condition.
• Eighty-four adults were included for study; 45 diagnosed with CFS by various criteria (yes, there are quite a few of them). They provided blood samples that were subject to analysis: "Targeted, broad-spectrum, chemometric analysis of 612 metabolites from 63 biochemical pathways was performed."
• Results: well, first various 'trigger' factors were linked to onset of CFS participants' symptoms. Biological triggers - "viral, bacterial, fungal/mold, and parasitic infections" - were most common but "no single infectious agent or other stressor was statistically more prevalent." There appear to be many [organic] roads to the development of CFS.
• 'A characteristic chemical signature' is something that many media outlets have jumped on to based on these results. Indeed, with some very pretty Venn diagrams included, there did appear to be some chemical 'signatures' that defined CFS vs. not-CFS.  The sorts of compounds seemingly involved related to the: "Sphingolipids, glycosphingolipids, phospholipids, purines, microbiome aromatic amino acid and branch chain amino acid metabolites." I'm particularly interested in the amino acid chemistry detected and how it may overlap with other findings [2].
• The relevance of those chemical signatures in terms of biological processes were quite diverse but led authors to conclude that "the metabolic features of CFS are consistent with a hypometabolic state." Some media outlets have referred to this as a 'semi-hibernation like state' where metabolism is somehow slowed down. I'm not so sure this is the most accurate definition given that hibernation normally implies a time-limit to such a state. Unfortunately, for many, CFS does not magically stop come the biological Spring. There is also mention of how the findings might relate to other research in CFS including a role for mitochondrial function (see here) and NAD (see here).

With some cautions attached to this line of work (see here), not least the quite small participant groups included for study and, I believe, the use of a single blood sample at one specific time point, this is interesting work. Added to a growing tide of research suggesting that if one looks, one might indeed find some biological issues associated with a diagnosis of CFS (see here for example), this is yet another stop in the journey towards understanding CFS is terms of biology not psychology. The next stop is of course independent replication.

"The study of larger cohorts from diverse geographical areas, and comparison with related medical disorders like depression and posttraumatic stress disorder, will be needed to validate the universality and specificity of these findings. The finding of an objective chemical signature in CFS helps to remove diagnostic uncertainty, will help clinicians monitor individualized responses to treatment, and will facilitate multicenter clinical trials." Big words that indeed require that independent replication, but the research future for CFS is already looking a little brighter as a result of the Naviaux findings.

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[1] Naviaux RK. et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2016 Aug 29. pii: 201607571.

[2] Georgiades E. et al. Chronic fatigue syndrome: new evidence for a central fatigue disorder. Clin Sci (Lond). 2003 Aug;105(2):213-8.

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Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, Baxter A, Nathan N, Anderson W, & Gordon E (2016). Metabolic features of chronic fatigue syndrome. Proceedings of the National Academy of Sciences of the United States of America PMID: 27573827