Benefits of Gut Microbiota Reconstitution by Beta 1,3-1,6 Glucans in Subjects with Autism Spectrum Disorder and Other Neurodegenerative Diseases

Abstract

Background: Aureobasidium pullulans (black yeast) AFO-202 strain-produced beta glucan, Nichi Glucan, has been shown to improve the behavior and sleep pattern along with an increase in α-synuclein and melatonin in children with autism spectrum disorder (ASD).

Objective: In this randomized pilot clinical study, we have evaluated the gut microbiota of subjects with ASD after consumption of Nichi Glucan.

Methods: Eighteen subjects with ASD were randomly allocated: six subjects in the control group (Group 1): conventional treatment comprising remedial behavioral therapies and L-carnosine 500 mg per day, and 12 subjects (Group 2) underwent supplementation with Nichi Glucan 0.5 g twice daily along with the conventional treatment for 90 days.

Results: Whole genome metagenome (WGM) sequencing of the stool samples at baseline and after intervention showed that among genera of relevance, the abundance of Enterobacteriaceae was decreased almost to zero in Group 2 after intervention, whereas it increased from 0.36% to 0.85% in Group 1. The abundance of Bacteroides increased in Group 1, whereas it decreased in Group 2. The abundance of Prevotella increased while the abundance of Lactobacillus decreased in both Group 1 and Group 2. Among species, a decrease was seen in Escherichia coli, Akkermansia muciniphila CAG:154, Blautia spp., Coprobacillus sp., and Clostridium bolteae CAG:59, with an increase of Faecalibacterium prausnitzii and Prevotella copri, which are both beneficial.

Conclusion: AFO-202 beta 1,3-1,6 glucan, in addition to balancing the gut microbiome in children with ASD and its role in effective control of curli-producing Enterobacteriaceae that leads to α-synuclein misfolding and accumulation, may have a prophylactic role in Parkinson's and Alzheimer's diseases as well.

Keywords: AFO-202; Enterobacteriaceae; autism; beta glucans; curli protein; neurodegenerative diseases.

Fig. 1

CONSORT flow diagram of the trial.

Fig. 2

Post intervention control versus post intervention treatment SEED Average values showing decrease in treatment (Nichi Glucan) group compared to control group for all the metabolites and metabolic functions.

Fig. 3

Genus abundance of major genera identified (A) Group (Gr.) 1 at baseline versus postintervention and (B) Group (Gr.) 2 at baseline versus postintervention. Phylum Firmicutes was the most abundant followed by Bacteroidetes.

Fig. 4

A) Significant decrease in abundance of Enterobacteriaceae in Group (Gr.) 2 compared to Group (Gr.) 1, postintervention (p = 0.045). B) Decrease in abundance of Bacteroides in Gr. 2 and increase in Gr. 1 postintervention. C) Increase in Prevotella in Gr. 1 and Gr. 2 postintervention and D) decrease in Lactobacillus in Gr. 1 and Gr. 2 postintervention. ^**significance p < 0.05

Fig. 5

Species abundance of major species analyzed; A) Group (Gr.) 1 at baseline versus postintervention and B) Group (Gr.) 2 at baseline versus postintervention. Fecalibacterium prausnitzii, Bifidobacterium longum, and Firmicutes bacterium CAG:124 represented the most abundant species.

Fig. 6

A) Significant decrease in abundance of E. coli in Group (Gr.) 2 compared to Group (Gr.) 1 (p = 0.04). B) Increase in abundance of Faecalibacterium prausnitzii in Gr. 2 compared to Gr. 1 (p = 0.54). C) Increase in Akkermansia muciniphila in Gr. 1 but decrease in Gr. 2 postintervention. D) Increase in Clostridium bolteae CAG:59 in Gr. 1 but decrease in Gr. 2 postintervention. ^**significance p < 0.05

Fig. 7

The above illustration explains, stepwise, the pathogenesis as well as the way beta glucan tackles each stage of the disease process: A, B) Enterobacteriaceae secretion of curli that causes misfolding of α-synuclein; its aggregation in enteric neuronal cells is tackled by (1) control of Enterobacteriaceae, (2) scavenging of the accumulated amyloids by activated natural killer cells, and (3) reconstitution of beneficial microbiome. C) The prion like propagation may not occur because the accumulation of curli proteins and amyloids is controlled at the level of production and aggregation (1) as well as clearing of already accumulated deposits (3). D) Deposition of Lewy bodies, amyloid fibrils, and misfolded αSyn are tackled by (4) microglial-based scavenging.