New evidences on the altered gut microbiota in autism spectrum disorders

Francesco Strati, Duccio Cavalieri, Davide Albanese, Claudio De Felice, Claudio Donati, Joussef Hayek, Olivier Jousson, Silvia Leoncini, Daniela Renzi, Antonio Calabrò, Carlotta De Filippo, Francesco Strati, Duccio Cavalieri, Davide Albanese, Claudio De Felice, Claudio Donati, Joussef Hayek, Olivier Jousson, Silvia Leoncini, Daniela Renzi, Antonio Calabrò, Carlotta De Filippo

Abstract

Background: Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD subjects frequently suffer from gastrointestinal abnormalities, thus implying a role of the gut microbiota in ASD gastrointestinal pathophysiology.

Results: Here, we characterized the bacterial and fungal gut microbiota in a cohort of autistic individuals demonstrating the presence of an altered microbial community structure. A fraction of 90% of the autistic subjects were classified as severe ASDs. We found a significant increase in the Firmicutes/Bacteroidetes ratio in autistic subjects due to a reduction of the Bacteroidetes relative abundance. At the genus level, we observed a decrease in the relative abundance of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella in the ASD cohort, while Collinsella, Corynebacterium, Dorea, and Lactobacillus were significantly increased. Constipation has been then associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by high levels of bacterial taxa belonging to Escherichia/Shigella and Clostridium cluster XVIII. We also observed that the relative abundance of the fungal genus Candida was more than double in the autistic than neurotypical subjects, yet due to a larger dispersion of values, this difference was only partially significant.

Conclusions: The finding that, besides the bacterial gut microbiota, also the gut mycobiota contributes to the alteration of the intestinal microbial community structure in ASDs opens the possibility for new potential intervention strategies aimed at the relief of gastrointestinal symptoms in ASDs.

Keywords: Autism spectrum disorders; Constipation; Gut microbiota; Metataxonomy; Mycobiota.

Figures

Fig. 1
Fig. 1
PCoA of bacterial beta diversity based on the a unweighted and b weighted UniFrac distances and c Bray-Curtis dissimilarity. Autistic and neurotypical subjects are coloured in orange and blue, respectively. The constipation status of the subjects is indicated according to different shapes, circles for non-constipated and triangles for constipated individuals
Fig. 2
Fig. 2
a Mean relative abundances (%) of Firmicutes and Bacteroidetes in autistic (AD) and neurotypical (NT) subjects; *p < 0.005, Wilcoxon rank-sum test on the Firmicutes/Bacteroidetes ratio. b Welch’s t test statistics of the relative abundances of bacterial phyla in autistic and neurotypical subjects. Orange bars indicate significant FDR-corrected p values adjusted for multiple comparison controlling the family-wise type I error rate
Fig. 3
Fig. 3
a Cladograms generated by LEfSe indicating differences in the bacterial taxa between autistic (AD) and neurotypical (NT) subjects. Nodes in orange indicate taxa that were enriched in AD compared to those in NT, while nodes in blue indicate taxa that were enriched in NT compared to those in AD. b LDA scores for the bacterial taxa differentially abundant between autistic (AD) and neurotypical (NT) subjects. Positive and negative LDA scores indicate the bacterial taxa enriched in NT and AD subjects, respectively. Only the taxa having a p < 0.01 (Wilcoxon rank-sum test) and LDA >2.0 are shown in the figure legend
Fig. 4
Fig. 4
Box plot representation of the relative abundances of bacterial genera correlating with the constipation status of the subjects enrolled in this study. Comparisons between a and b constipated (C) and non-constipated (NC) autistic subjects and (c) constipated (C) and non-constipated (NC) neurotypical subjects; Asterisk indicates FDR-corrected p < 0.05, Wilcoxon rank-sum test
Fig. 5
Fig. 5
PCoAs of fungal beta diversity based on a weighted UniFrac distance and b Bray-Curtis dissimilarity. The right panel of the graphs a and b shows the same PCoA coordinates with the most abundant OTUs superimposed as coloured squares, with the size being proportional to the mean relative abundance of the taxon across all samples (grey dots). Autistic and neurotypical subjects are colored in orange and blue, respectively. The constipation status of the subjects is indicated according to different shapes, circles for non-constipated and triangles for constipated individuals

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