Saturday, 16 July 2016

Increased microbial translocation in ME/CFS

"The cause of ME/CFS [myalgic encephalomyelitis/chronic fatigue syndrome] is unknown, but gut dysbiosis could be contributing to some of the symptoms and their severity. Developing therapeutic interventions aimed at reducing local inflammation, restoring gastrointestinal tract immunity and integrity and modifying the intestinal microbiome may ameliorate ME/CFS symptoms in a number of affected patients."

Those were the important conclusions reported by Ludovic Giloteaux and colleagues [1] (open-access) who "profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from stool as well as inflammatory markers from serum for cases (n = 48) and controls (n = 39)." Authors recount how all 'cases' (participants) fitted the "Fukuda diagnostic criteria" for CFS/ME but "most, perhaps all, also fit the description of SEID [Systemic Exertion Intolerance Disease]." We're also told that a majority of participants with ME/CFS "self-reported gastrointestinal disturbances such as constipation, diarrhea, or intestinal discomfort" something perhaps not unfamiliar to the peer-reviewed research domain (see here).

Looking at inflammatory markers as well as the composition and diversity of those trillions of wee beasties that call us home (the gut microbiome), Giloteaux et al reported some important differences between their groups that might even be considered 'diagnostic' at some point in the future (emphasis on 'some point'). "[The] gastrointestinal tract of ME/CFS  patients is a pro-inflammatory environment" is another of their observations; indeed, based on the idea that: "Abnormal immune activation can be caused by translocation of microbes from an inflamed gut" and reporting elevations in some of the blood markers potentially pertinent to this process. Said microbial translocation (MT) was evidenced by: "(i) significantly raised levels of plasma LPS [lipopolysaccharide] and (ii) significantly higher levels of sCD14 [soluble CD14] and LBP [LPS-binding protein], as indicators of direct LPS stimulation." Interestingly however: "Levels of hsCRP [high-sensitivity C-reactive protein] were higher in the ME/CFS population in comparison to healthy controls... but the difference was not statistically significant."

Examination of stool samples from study participants also found some potentially important differences between the groups as "less diversity as well as increases in specific species often reported to be pro-inflammatory species and reduction in species frequently described as anti-inflammatory" were found in the ME/CFS group. Of particular note were "lower levels of the genus Faecalibacterium, a member of the Ruminococcaceae in the ME/CFS population" and that "Proteobacteria were more abundant in ME/CFS patients than in controls." Minus any sweeping generalisations, such combined findings have been reported in cases of inflammatory bowel disease (IBD) among other things. Utilising a machine-learning approach (something we've seen before on this blog) authors were also "mostly successfully classified into healthy and ME/CFS groups" on the basis of the inflammatory and microbiome data with a little more investigation required.

This is of course not the first time that the gut microbiome has been 'implicated' in cases of ME/CFS (see here). The application of the 'yuck factor 10' that is the faecal microbiota transplantation as one effort to alter the gut microbiome in cases of ME/CFS has also been mentioned too (see here). These latest results add to the interest and indeed, the idea that the gut might be a central organ of either cause or effect when it comes to at least some cases of ME/CFS (see here and see here). But I might also add there is more to do in this area. Giloteaux et al talk a lot about gut barrier integrity as being implicated but didn't directly measure permeability or by how much...

Finally, I do think due credit should be given to some of the research pioneers upon which the Giloteaux findings are based. I'm thinking specifically of Michael Maes of NIOF fame (see here) who has been quite consistently talking about "increased translocation of LPS from gram negative bacteria with subsequent gut-derived inflammation" in cases of CFS/ME and importantly, what could be potentially done about it [2]. It appears that replicative science might indeed be on his, and his research teams', side. And he just keeps going (see picture).


[1] Giloteaux L. et al. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2016; 4: 30.

[2] Maes M. & Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

---------- Giloteaux L, Goodrich JK, Walters WA, Levine SM, Ley RE, & Hanson MR (2016). Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 4 (1) PMID: 27338587