Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-lasting neurological disorder often triggered by viral infections, including COVID-19, and marked by severe fatigue, post-exertional malaise, and sleep disturbances. With nearly 50% of COVID-19 survivors reporting ME/CFS-like symptoms, effective and accessible treatments are needed. 

Because gut issues are common in post-COVID ME/CFS, probiotics and synbiotics (a combination of live microorganisms and substrates selectively utilized by host microorganisms to confer health benefits) have been proposed as safe, low-cost options to restore the gut microbiota ecosystem. To date, there are no human studies evaluating the efficacy of synbiotics in clinical settings. 

Ranisavljev and colleagues conducted a study published in European Journal of Nutrition to evaluate the safety and efficacy of medium-term supplementation with a synbiotic mixture (made of Humiome®L. rhamnosus DSM 32550, Humiome® L. plantarum DSM 34532, Humiome®B. lactis DSM 32269, B. longum DSM 32946, fructooligosaccharides and zinc) on symptoms and clinical outcomes in post-COVID-19 ME/CFS patients.

The trial was conducted at the University of Novi Sad (Serbia) and supported by dsm-firmenich (Kaiseraugst, Switzerland), that supplied the synbiotic mixture and placebo utilized in the study. 

Results

Researchers administered a daily dosage of synbiotic mixture and placebo to 12 patients (experimental group) and 14 patients (control group), respectively and then measured several outcomes: levels of fatigue, how well people could tolerate exercise, and whether they experienced any side effects. In a subset of patient tissue levels of choline, creatine and N-acetyl aspartate were determined in specific regions of skeletal muscle and brain. They also asked participants to report common post-COVID symptoms such as loss of smell or taste, breathing difficulties, body aches, or brain fog.

Fatigue was assessed in detail, including physical tiredness, mental tiredness, reduced motivation, and problems carrying out daily activities. Exercise tolerance was tested by measuring how long participants could walk on a treadmill before exhaustion. In a smaller group, brain and muscle scans were also carried out to check for changes in certain key chemicals related to energy and brain function.

After three months of treatment, participants taking the synbiotic reported significant reduction of general, physical, and mental fatigue, compare to baseline levels. The placebo group also showed improvements, particularly in general and physical fatigue as well as reduced activity. Moreover, the synbiotic mixture led to a marked reduction in post-exercise malaise after three months and was more effective than placebo in attenuating this symptom. There was also a trend suggesting that synbiotic could be superior to placebo to reduce problems with concentration. 

Overall tissue levels of choline (a compound required for normal neurotransmission) did not change in either group, but the synbiotic significantly increased choline in the thalamus compared with placebo. The synbiotic treatment also increased levels of creatine, an important factor in sustaining energy in tissues with high metabolic activity, across many brain and muscle regions, whereas the placebo showed almost no effect. Notably, synbiotic intake led to greater increases in creatine within the left frontal white and grey matter compared with placebo, highlighting its potential to enhance tissue energy metabolism. 

Furthermore, synbiotic intake led to significant increases in N-acetylaspartate (NAA), a marker of neuronal health, across several brain regions, while the placebo group showed no changes except for one region after 12 months. Despite these metabolic improvements, researchers found no significant difference when compared changes in NAA levels between the synbiotic and placebo groups over time. 

Overall, these results support earlier evidence showing that probiotics and prebiotics can have beneficial effects in ME/CFS, while extending these findings to a longer supplementation period, a more detailed assessment of tissue metabolism, and patients specifically affected by post-COVID-19 ME/CFS.

Conclusions

The present study showed that a three-month treatment with the synbiotic mixture containing specific probiotic strains (L. rhamnosus, L. plantarum, B. lactis, Bifidobacterium longus), prebiotics (fructooligosaccharides) and zinc, improved tissue metabolism and reduced post-exercise malaise in patients with post-COVID-19 fatigue syndrome, potentially through neuroprotective effects. Although further studies are needed to confirm the results in broader ME/CFS populations and to investigate related immune and cognitive biomarkers, these findings are promising in addressing the widespread issue of ME/CFS following the COVID-19 pandemic.