The gut microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS), by Rahel S König, Werner C Albrich, Christian R Kahlert, Lina Samira Bahr, Ulrike Löber, Pietro Vernazza, Carmen Scheibenbogen, Sofia K Forslund in Front Immunol 2022 Jan 3;12:628741 [doi: 10.3389/fimmu.2021.628741]
Review abstract:
Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear.
The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses.
Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS.
Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway.
We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria.
Table 2 Possible treatment affecting the microbiome in ME/CFS patients
1. FECAL MICROBIOTA TRANSPLANTATION (FMT)
Findings - A beneficial response in 70% of ME/CFS patients to a rectal infusion of a specific combination of bacteria has been reported, but all patients suffered from gastrointestinal symptoms (20). Massive improvement, also concerning energy levels of the patients, have been seen in patients undergoing FMT, also comparing to probiotics (31).
Ideas for future research -We recommend larger studies with more patients and at different stages of the disease undergoing FMT observing the energy level and other symptoms after the treatment.
2. PROBIOTICS
Q. Are there any positive effects in the symptoms of ME/CFS by manipulating the gut microbiota of the patients?
Findings – Until now, there is no evidence for an amelioration of the core symptoms of ME/CFS patients through the use of probiotics, although significant changes in the gut have been observed in different probiotic studies (32).
Ideas for future research – In future probiotic studies it would be interesting to take biopsies of the gut instead of taking stool samples, as well as coupling metagenomic and transcriptomic analysis. In particular interventions increasing abundance of SCFA producers should be investigated.
3. FASTING DIETARY INTERVENTIONS
Q. Are different modes of fasting able to improve symptoms in ME/CFS patients?
Findings – Until now there is no evidence for fasting dietary or fasting mimicking interventions in ME/CFS.
Ideas for future research – Projection of findings from fasting interventions in other diseases may motivate such trials also in ME/CFS.
4. OTHER POTENTIALLY GUT MICROBIOME MEDIATED APPROACHES
Q. Is Vitamin B1 and Ginseng supplementation safe and effective in ME/CFS?
Findings – A double-blind randomized-controlled cross-over study with 40 IBD patients suffering from severe fatigue investigated the effects of a 20-day high dose thiamine (Vitamin B1) supplementation and showed a significant treatment effect regarding fatigue (33)
- Oral administration of ginseng has been shown to have anti-fatigue properties in ME/CFS, MS-related fatigue and cancer-related fatigue in several blinded randomized-controlled studies (34–37)
- Acupuncture and moxibustion (traditional Chinese medicine practices) to relieve symptoms of fatigue have been extensively investigated, but study quality is partially low (38–40)
Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play.
An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.
