Altered gut microbiota and microbial metabolism in children with hepatic glycogen storage disease: a case-control study

Background: Accumulating evidence has demonstrated that gut microbiota dysbiosis correlated with altered metabolism are implicated in liver metabolic diseases. However, data on pediatric hepatic glycogen storage disease (GSD) are limited. Here, we aimed to investigate the features of the gut microbiota and metabolites in hepatic GSD children from China.Methods: Totals of 22 hepatic GSD patients and 16 age-and gender-matched healthy children were enrolled from the Shanghai Children's Hospital, China. Pediatric GSD patients were confirmed as having hepatic GSD via genetic diagnosis and/or liver biopsy pathology. The control group comprised children without any history of chronic diseases or clinically relevant GSD or symptoms of any other metabolic diseases. The baseline characteristics of the two groups were gender-and age-matched matched using chi-squared test and the Mann-Whitney U test, respectively. The gut microbiota, bile acids (BAs), and short chain fatty acids (SCFAs) were determined from the feces using 16S ribosomal RNA (rRNA) gene sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and gas chromatography-mass spectrometry (GC-MS), respectively.Results: The alpha diversity of fecal microbiome was significantly lower in hepatic GSD patients [observed species richness (Sobs): P=0.011; abundance-based coverage estimator (ACE): P=0.011; Chao: P=0.011; Shannon: P<0.001], and their microbial community was more distanced from that of the control [principal coordinate analysis (PCoA) on genus level, unweighted UniFrac: P=0.011]. Relative abundances of phyla Firmicutes (P=0.030) and Bacteroidetes (P=0.029), families Lachnospiraceae (P=0.012), Ruminococcaceae (P=0.008), and Peptostreptococcaceare (P=0.031), genera Blautia (P=0.017), Eubacterium_hallii_group (P=0.032), and Faecalibacterium (P=0.017) were decreased, whereas phyla Actinobacteria (P=0.033), Proteobacteria (P=0.049), families Bifidobacteriaceae (P=0.030), Lactobacillaceae (P=0.034), and Veillonellaceae (P=0.033), genera Lactobacillus (P=0.011), Enterobater (P=0.034), and Veillonella (P=0.014) were increased in hepatic GSD. Altered microbial metabolisms were characterized by increased abundances of primary BAs (P=0.009) and decreased concentrations of SCFAs in hepatic GSD children. Furthermore, the altered bacterial genera were correlated with the changes of both fecal BAs and SCFAs.Conclusions: The hepatic GSD patients in this study presented with gut microbiota dysbiosis which correlated with altered BAs metabolism and fecal SCFAs changes. Further studies are needed to investigate the driver of these changes mediated by either the genetic defect, disease status, or diet therapy.