Randomised trial of Aureobasidium pullulans-produced beta 1,3-1,6-glucans in patients with Duchenne muscular dystrophy: Favourable changes in gut microbiota and clinical outcomes indicating their potential in epigenetic manipulation

Objective: Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder that leads to increasing muscle weakening and early death. Steroids, the standard treatment of choice in slowing down disease progression, are plagued with adverse effects. Following anti-inflammatory and anti-fibrotic outcomes of an Aureobasidium pullulans strain N-163-produced beta 1,3-1,6-glucan food supplement in clinical and pre-clinical studies of DMD, herein we report their implications on the gut microbiome in patients with DMD. Design: Twenty-seven patients with DMD were included in the pilot study (Control [n=9], N-163 [n=18]) which had previously reported the clinical decrease in inflammatory and fibrosis biomarkers. For the current study, whole genome metagenomic sequencing was performed in pre- and post N-163 intervention faecal samples of each of these participants. Results: After N-163 beta-glucan administration, the constitution of the gut microbiome in all the participants was modified to one with positive outcomes on health. There was an increase in butyrate-producing species such as Roseburia and Faecalibacterium prausnitzii. There was a decrease in harmful bacteria associated with inflammation such as enterobacteria and Alistipes. Conclusion: Beneficial reconstitution of the gut microbiome after N-163 beta-glucan administration, in addition to their implications in anti-inflammatory and anti-fibrotic outcomes, require further in-depth exploration on their roles in epigenetic manipulation.