Reacción a "Reactions: two studies link microbiome changes to chronic fatigue syndrome"

In both papers the authors study the specificities of the microbiota in myalgic encephalomyelitis/chronic fatigue syndrome. This disease has no specific diagnostic criteria and it is sometimes a problem to label it correctly. It is partly related to fibromyalgia and is often lumped with it. So one of the main limitations is a correct diagnosis.   

The two studies are of high scientific quality because of the number of patients recruited, the techniques used and the bioinformatic methods they have developed.  

The study populations are different. The study by Guo et al. includes patients with irritable bowel symptoms (self-referred, so they do not have a secure diagnosis either) and patients without bowel symptoms. The study by Xiong et al. differentiates between patients with a short evolution of four years and those with a long evolution of ten years.   

Both studies use healthy controls from the same environment and location. Both focus on the composition of the microbiota, but above all on its function, in particular by analysing short-chain fatty acids, which are metabolites exclusive to bacteria—humans do not have the capacity to synthesise them. What is most striking is that all patients have a lower concentration of butyrate and propionate in their faeces, which is blamed for the inflammation and low metabolism of these patients. There is also a striking deficiency of bacterial respiration.  

This disease, or this set of diseases, has always had an onset of symptoms linked to a systemic viral infection, which most patients mention. This is supposed to trigger intestinal alterations (remember that some viruses are bacteriophages that could contribute to the balance of the intestinal ecosystem). In the study by Xiong et al. the authors comment that four years after the disease, the differences in the composition of the gut microbiota are much more pronounced than after ten years. This could be a sign of the ability of the microbiota to recover its initial diversity over time.  

It is also important to differentiate between patients who report an irritable bowel and those who tend to be more constipated, as this could certainly indicate different microbiota scenarios. 

The major novelty is that the authors demonstrate with solid conclusions that in the patients’ group, the production of butyrate is lowered and related to a lower amount of Faecalibacterium and Eubacterium. In view of these results, an intervention should be considered, either with external administration of butyrate or of the bacteria that produce it. Finally, these results provide indicators that we could measure to monitor the evolution of this disease, which so far hasn’t been associated with clinical measurements outside the normal range.  

Both studies have taken into account the main limitations of this pathology, but as mentioned above, perhaps the most relevant is the lack of diagnostic criteria and the great variety of symptoms presented by patients, which prevents us from having uniform cohorts. On the other hand, the contribution of the microbiota to this pathology has long been suspected, but the human factor has yet to be established. Perhaps, like bacteria, human cells are respiration-deficient and metabolism is slowed down as a result. There is certainly still a lot to be discovered in this disease, but for the first time a different intestinal metabolism has been found in patients and healthy controls in relation to butyrate, which is already known to be a source of energy for the cells of the intestinal mucosa.