Naviaux en collega's concluderen op basis van de analyse van 612 metabolieten (63 "pathways')
dat het lichaam van patiėnten in response op een (fysiek) trauma in een "diepe winterslaap" schiet,
gepaard gaande met een sterk verlaagde stofwisseling, teneinde het lichaam te helpen overleven.
Dat beschermingsmechanisme (dat in wormen bekend staat als dauer) gaat ten koste van pijn etc.
Naviaux en collega's vonden afwijkingen in de stofwisseling van 20 biologische "pathways".
Tachtig procent van de abnormaliteiten had betrekking op een verminderde stofwisseling.
Er waren naast (9) overeenkomsten ook duidelijke verschillen tussen mannen en vrouwen met CVS.
25% van de afwijkingen in de stofwisseling betrof CVS-algemene afwijkingen,
maar liefst 75% van de afwijkingen betrof patiėnt-/mens-specifieke afwijkingen.
Op basis van 8 metabolieten konden de auteurs 94% van de mannelijke patiėnten juist classificeren,
en aan de hand van 13 metabolieten 96% van de vrouwelijke CVS-patiėnten.
In de media
Het kritische tegengeluid in bovenstaande artikelen komt van
prof. Andrew Macintosh
(pyschiater)
die door, hoe kan het ook anders, op het Science Media Centre een platform krijgt (klik hier).
Metabolic features of chronic fatigue syndrome.
PPNAS. 2016 Aug 29. doi:10.1073/pnas.1607571113
Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L,
Baxter A, Nathan N, Anderson W, Gordon E.
Significance
Chronic fatigue syndrome is a multisystem disease that causes long-term pain and disability.
It is difficult to diagnose
because of its protean symptoms and the lack of a diagnostic laboratory test.
We report that
targeted, broad-spectrum metabolomics of plasma
not only revealed a characteristic chemical signature
but also revealed an unexpected underlying biology.
Metabolomics showed that
chronic fatigue syndrome is a highly concerted hypometabolic response
to environmental stress
that traces to mitochondria and
was similar to the classically studied developmental state of dauer.
This discovery opens a fresh path for the rational development of new therapeutics and
identifies metabolomics as a powerful tool
to identify the chemical differences that contribute to health and disease.
Abstract
More than 2 million people in the United States
have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
We performed targeted, broad-spectrum metabolomics
to gain insights into the biology of CFS.
We studied a total of 84 subjects using these methods.
Forty-five subjects (n = 22 men and 23 women)
met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria.
Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls.
Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21-67 y).
Females were 52 (±2.5) y old (range, 20-67 y).
The Karnofsky performance scores were
62 (±3.2) for males and
54 (±3.3) for females.
We targeted 612 metabolites in plasma from 63 biochemical pathways
by hydrophilic interaction liquid chromatography, electrospray ionization, and
tandem mass spectrometry in a single-injection method.
Patients with CFS showed abnormalities in 20 metabolic pathways.
Eighty percent of the diagnostic metabolites were decreased,
consistent with a hypometabolic syndrome.
Pathway abnormalities included
sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin,
branch chain amino acid, peroxisomal, and mitochondrial metabolism.
Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of
94% [95% confidence interval (CI), 84-100%] in males using eight metabolites and
96% (95% CI, 86-100%) in females using 13 metabolites.
Our data show that despite the heterogeneity of factors leading to CFS,
the cellular metabolic response in patients was homogeneous, statistically robust, and
chemically similar to the evolutionarily conserved persistence response to environmental stress
known as dauer.
Keywords:
Chronic fatigue syndrome, metabolomics, mitochondria, dauer, cell, danger response
HTML-versie:
http://www.pnas.org/content/early/2016/08/24/1607571113.long
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