Dietary treatment promotes gut microbial community changes in subjects affected by glycogenosis type 1

Background: The glycogen-storage diseases (GSDs) are caused by enzyme defects of glycogen degradation. These enzymes are mainly localized in the liver. Hepatomegaly and hypoglycemia are the principal abnormalities. The glycogen storage disease Ia and Ib are due to the defects of the glucose-6-phosphatase and glucose-6-phosphate translocase, respectively. The aim of dietary treatment is to prevent hypoglycemia and suppress secondary metabolic complications, by the intake of slow-release carbohydrates. Such a dietary intervention could affect the availability of substrates for microbial fermentation. In this study, we compared the gut microbiota composition and microbial metabolite production (i.e. short chain fatty acids -SCFAs-) of subjects with glycogenosis type 1 and healthy subjects, sex- and age-matched. Methods: Nine GSD1 subjects (6 males, age range 4-38 years old) and 12 healthy controls (CTR) were enrolled. We assessed dietary intake and performed gut microbiota analysis by next-generation sequencing using V3–V4 hypervariable 16S rRNA genomic region. Fecal SCFAs were quantified by gas chromatography. Results: Alpha-diversity analysis revealed a significant reduction in microbial richness and evenness in the GSD group compared with CTR (PD whole tree, p = 0.03; observed species p = 0.02; Shannon, p = 0.002). Phylogenetic analysis highlighted a significant separation of gut microbiota according to both unweighted (p=0.004) and weighted Unifrac distances (p=0.01). In particular, GSD subjects were characterized by an increase in the relative abundance of Enterobacteriaceae (p=0.006) and Veillonellaceae (p=0.01), whereas CTR group was enriched in Ruminococcaceae (p=0.001). SCFAs quantification revealed an increase of fecal acetate and propionate in GSD subjects. Discussion: Despite GSD diet is enriched in resistant starch, usually considered good substrates for beneficial microbes, we found a dramatic increase in Proteobacteria. This phylum, and in particular Enterobacteriaceae, had been suggested to exert pro-inflammatory activity both locally, at the gastrointestinal mucosa, and systemically. Indeed, GSD subjects are at higher risk to develop chronic inflammatory bowel diseases. Whether our findings represent an effect of the disease itself, or a consequence of the diet is still unclear.