Discussion
irritable bowel syndrome, fatigue, post-exertional malaise, neurocognitive deficits, dysbiosis, CFS
IRRITABLE BOWEL SYNDROME, DISEASE, PATHOPHYSIOLOGY, NEUROLOGICAL DISORDERS
To our knowledge, this is the first randomized study to evaluate the effect of FMT on the HRQOL of patients with CFS. In this study, the IOM criteria were utilized to diagnose CFS. Several other case definitions have emerged. In 1994, Fukuda et al. introduced recommendations for the clinical evaluation of fatigued persons with key symptoms including post-exertional malaise, neurocognitive deficits and unrefreshing sleep [There is no objective test to measure fatigue or HRQOL, but by utilizing a patient-reported outcome measure, professionals are able to gather insights with direct relevance to the patient questioned. Several different methods are applied to assess quality of life and there is no consensus on the best technique for determining patient well-being. In certain patient populations, substantial variability among commonly utilized questionnaires has been reported and discrepancies have been particularly apparent as data have been evaluated at the individual level. To avoid bias, we decided to apply an array of HRQOL measures [FMT is commonly administered by three modalities: colonoscopy, oral capsules and gastroscope or nasojejunal probe [In previous studies, HRQOL of CFS patient has been remarkably lower compared to the general population. In this study, 10 patients out of 11 reported their baseline VAS fatigue score over 50 (scale 0–100). The average total MFIS score in the FMT and placebo groups were 59.6 and 61.0, respectively. Besharat and colleagues reported mean MFIS score 46.7 in CFS patients compared to 25.4 in healthy controls [The 15D is a standardized measure of HRQOL that can be used both as a profile and single index score measure representing overall HRQOL. It generically assesses health status in terms of 15 dimensions not specific to any patient group or disease. The index score (range 0–1) is calculated by using a set of population-based utility weights [Our main hypothesis was that gut dysbiosis might explain the pathomechanism of CFS and that gut microbiota intervention with FMT could relieve CFS-related symptoms. We exclusively selected the CFS patients from a large group of patients with fatigue caused by other reasons. The study subjects were randomly allocated in a double-blind fashion to the FMT or the placebo groups. Colonoscopy was applied to administer the FMT. In a previous study using the same FMT procedure without prior antibiotic pre-conditioning, one dose of FMT was found to alter the microbiota of irritable bowel syndrome patients to resemble that of the donor [During the six-month follow up, the HRQOL was assessed twice, and four different self-reported questionnaires were utilized. In this study, we could not find improvement in the HRQOL scores after the single FMT from an universal donor. There were no statistically significant differences in the characteristics or the baseline HRQOL scores between the FMT and the placebo groups. Compared to the baseline VAS and MFIS scores, the differences in 1- and 6-months scores were statistically non-significant in both the FMT and the placebo groups. There was a slight, but statistically non-significant improvement in the 1-month MFIS physical subscale scores. However, such tendency was not present in VAS scores. The individual patient’s EQ-5D-3L profiles remained practically unaltered throughout the study. The 15D profiles in the FMT and the placebo groups did not change during the follow-up. The limited number of study subjects inhibits the generalizability of these results. There was only one male subject in the study. To exclude gender-based bias, we re-analyzed the data after having the male subject removed from the analysis. The results did not change: no statistically significant difference was found between the FMT and the placebo groups. This pilot study did not confirm nor exclude the possibility that FMT could have some effect on the HRQOL of patients with CFS. The pathomechanism of CFS remains unknown and gut microbiota may affect the pathophysiology of several neurological disorders. Further research and larger trials including also evaluation of changes in bacterial composition are needed to discover the underlying mechanisms of CFS.