Altered Gut Microbiota in a Fragile X Syndrome Mouse Model

Abstract

The human gut microbiome is the ecosystem of microorganisms that live in the human digestive system. Several studies have related gut microbiome variants to metabolic, immune and nervous system disorders. Fragile X syndrome (FXS) is a neurodevelopmental disorder considered the most common cause of inherited intellectual disability and the leading monogenetic cause of autism. The role of the gut microbiome in FXS remains largely unexplored. Here, we report the results of a gut microbiome analysis using a FXS mouse model and 16S ribosomal RNA gene sequencing. We identified alterations in the fmr1 KO2 gut microbiome associated with different bacterial species, including those in the genera Akkermansia, Sutterella, Allobaculum, Bifidobacterium, Odoribacter, Turicibacter, Flexispira, Bacteroides, and Oscillospira. Several gut bacterial metabolic pathways were significantly altered in fmr1 KO2 mice, including menaquinone degradation, catechol degradation, vitamin B6 biosynthesis, fatty acid biosynthesis, and nucleotide metabolism. Several of these metabolic pathways, including catechol degradation, nucleotide metabolism and fatty acid biosynthesis, were previously reported to be altered in children and adults with autism. The present study reports a potential association of the gut microbiome with FXS, thereby opening new possibilities for exploring reliable treatments and non-invasive biomarkers.

Keywords: autism spectrum disorders; biomarkers; drug development; drug targets; fragile X syndrome; gut microbiota; mouse models; neuroinflammation.

FIGURE 1

Operational Taxonomic Units (OTU) based analysis according to panel (A) sample type and to panel (B) genotype, for the phyla and genera taxonomic levels of bacteria. Principal coordinates analysis (PCoA) was used for calculation of beta diversity of the OTU-based bacterial communities. In panel (C) are presented the PCoA plots according to the sample type (cecum and feces) and in panel (D) to the genotype (FXS and WT).

FIGURE 2

Spearman rank correlation for bacterial genera identified on the fmr1 KO2 mouse gut microbiome. Red squares indicate a positive correlation, respectively (as is shown in the colored scale).

FIGURE 3

Microbial metabolic pathway prediction on the fmr1 KO2 mouse gut microbiome. Samples from cecum (A) and feces (B) were analyzed for the prediction of significantly altered metabolic pathways.