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

C-sections and obesity

This is an extension post to a topic previously discussed on this blog and its sister blog in relation to your route of entry into the world potentially being correlated with later health and ill-health risk.

The header in the UK Sunday Times on 20 November 2011 was 'caesarean babies have greater risk of obesity'. We are told through this article that babies born through planned c-sections are more likely to become obese. The reason: higher levels of fats in the liver as a result of a malfunction of the metabolic processes which allows people to handle fats according to one of the authors, Prof. Neena Modi of Imperial College, London. It appears that the often traumatic journey from snug warm cocoon to big wide world via the birth canal, and all the hormones and chemicals involved in this process, might have lots of different lasting effects on baby. That's before you even reach the stage of cord clamping and when to do it.

I can't post a link to the study in question reporting these findings because I can't find it (yet). What we do know is that scanning livers of 62 babies and correlating with maternal body mass index (BMI) and birth route (vaginal, emergency c-section, planned c-section) revealed some interesting trends. So, mum's weight seemed to have an effect on liver fat content but only when birth was by planned c-section. This might have some interesting implications for the message being put out about larger mums predisposing to larger offspring.

The Imperial team (no, not that Imperial) are no strangers to this type of research as evidenced by a recent paper of theirs suggesting that fat in liver (intrahepatocellular lipid) of babies might be correlated with maternal body mass index (BMI). I assume that this latest research is an extension of their tried and tested investigative techniques.

Going back to my previous posts on c-sections, it is interesting that a few trends seem to be appearing. Labour and all the biochemical changes a woman's body makes when it is time to give birth seem to be important when it comes to a baby's subsequent risk of obesity (fatty liver anyway) and coeliac disease. Distinguishing emergency c-sections from planned c-sections, where one would assume that many of those biochemical changes are already starting to take place despite the fact that entry into the world is via a different port, also seems to be important.

I do also wonder about that favourite topic of mine 'bacteria' and whether babies who need to be delivered by emergency c-section might have already taken a few mouthfuls of the good stuff as a result of their partial journey down the birth canal? Does this mean that a good dose of mum's bacteria should accompany all planned c-sections? (Not that I'm offering any clinical advice!)