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Clinical Trial
, 16 (1), 24

Open-label Pilot for Treatment Targeting Gut Dysbiosis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Neuropsychological Symptoms and Sex Comparisons

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Clinical Trial

Open-label Pilot for Treatment Targeting Gut Dysbiosis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Neuropsychological Symptoms and Sex Comparisons

Amy Wallis et al. J Transl Med.

Erratum in

Abstract

Background: Preliminary 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.

Methods: An 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.

Results: Large 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.

Conclusions: Results 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.

Keywords: Antibiotic; Chronic fatigue syndrome; Clinical outcomes; Gut dysbiosis; Microbiota-gut-brain; Myalgic encephalomyelitis; Neuropsychological symptoms; Open-label pilot; Probiotic; Sex comparisons; Streptococcus; Treatment.

Figures

Fig. 1
Fig. 1
Participant flow diagram
Fig. 2
Fig. 2
Effect size estimates (μp2 = partial eta squared) and confidence intervals (C.I.) for clinical, microbial and lactate outcomes for the total sample across time. The cut-off for large effects (μp2 > .14) is indicated by the dotted line. Asterisks (*) are used to identify primary outcomes. Change in mean scores for all clinical outcomes (sleep, mood, cognitive and other) were in the direction of improvement at post-intervention. Change in mean scores on microbiota variables reduced at post-intervention unless indicated (^). The d:l lactate variable ratio increased at post-intervention (^). See Additional file 1: Table S1 for baseline and post descriptive statistics for each variable
Fig. 3
Fig. 3
Change in Streptococcus (a) count, (b) relative abundance within aerobic bacteria (RAaerobe), and (c) relative abundance within total bacteria (RAtotal) for individual cases before and after intervention. formula image indicates mean scores at baseline and post

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