Abstract
BackgroundPreliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of d-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS.MethodsAn open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces) and with a count greater than 5% of the total count of aerobic microorganisms. The 4-week treatment protocol included alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily and probiotic (d-lactate free multistrain probiotic, 5 × 1010 cfu twice daily). 2 × 2 repeated measures ANOVAs were used to assess sex-time interactions and effects across pre- and post-intervention for microbial, lactate and clinical outcomes. Ancillary non-parametric correlations were conducted to examine interactions between change in microbiota and clinical outcomes.ResultsLarge treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine d:l lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females.ConclusionsResults support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population. Streptococcus spp. are not the primary or sole producers of d-lactate. Further investigation of lactate concentrations are needed to elucidate any role of d-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment.Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366933&isReview=true
Highlights
Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neu‐ rological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Advances in metabolomics methods would be useful to monitor functional changes during probiotic supplementation in ME/CFS patients. These results add to the accumulating evidence that microbiota–gut–brain interactions play a role in the clinical presentations of a subgroup of ME/CFS patients
Precise mechanisms remain to be determined because results for d-lactate challenged the premise that Streptococcus species are the primary producers of d-lactic acid
Summary
Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neu‐ rological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The history of diagnostic discrepancies (see [1,2,3,4]) is reflected in varied prevalence rates between .08 and 2.6% [5,6,7,8,9,10,11] but the burden on both the patient, their family and society is unequivocal [12] This burden is a result of the devastating impact that the condition has on the patient’s daily, occupational and social functioning [13,14,15] but can be attributed to the direct cost of medical care that is often exacerbated by misdiagnosis and unclear treatment pathways [16, 17]. Accumulating evidence suggests that microbial imbalances (whether consequential or causative) should not be viewed in isolation as they may be relevant for multiple ME/CFS symptoms, including but not limited to neurological manifestations
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