Hepatic glycogen storage diseases are associated to microbial dysbiosis

Abstract

Introduction The gut microbiome has been related to several features present in Glycogen Storage Diseases (GSD) patients including obesity, inflammatory bowel disease (IBD) and liver disease. Objectives The primary objective of this study was to investigate associations between GSD and the gut microbiota. Methods Twenty-four GSD patients on treatment with uncooked cornstarch (UCCS), and 16 healthy controls had their faecal microbiota evaluated through 16S rRNA gene sequencing. Patients and controls were ≥3 years of age and not on antibiotics. Faecal pH, calprotectin, mean daily nutrient intake and current medications were recorded and correlated with gut microbiome. Results Patients’ group presented higher intake of UCCS, higher prevalence of IBD (n = 04/24) and obesity/overweight (n = 18/24) compared to controls (n = 0 and 06/16, respectively). Both groups differed regarding diet (in patients, the calories’ source was mainly the UCSS, and the intake of fat, calcium, sodium, and vitamins was lower than in controls), use of angiotensin-converting enzyme inhibitors (patients = 11, controls = 0; p-value = 0.001) multivitamins (patients = 22, controls = 01; p-value = 0.001), and mean faecal pH (patients = 6.23; controls = 7.41; p = 0.001). The GSD microbiome was characterized by low diversity and distinct microbial structure. The operational taxonomic unit (OTU) abundance was significantly influenced by faecal pH (r = 0.77; p = 6.8e-09), total carbohydrate (r = -0.6; p = 4.8e-05) and sugar (r = 0.057; p = 0.00013) intakes. Conclusions GSD patients presented intestinal dysbiosis, showing low faecal microbial diversity in comparison with healthy controls. Those findings might be due to the disease per se , and/or to the different diets, use of UCSS and of medicines, and obesity rate found in patients. Although the main driver of these differences is unknown, this study might help to understand how the nutritional management affects GSD patients.

Proteobacteria Overgrowth and Butyrate-Producing Taxa Depletion in the Gut Microbiota of Glycogen Storage Disease Type 1 Patients

“…During the last decade, a healthy gut microbiota has been typically characterized by members of the phyla Bacteroidetes and Firmicutes, and their genera are believed to be the main responsible bacteria for positive biodiversity in the human gut [25], as their balanced abundances and metabolite productions protect the intestinal trait, help digestion and modulate the host innate immune system [26]. In agreement with Colonetti and coworkers [27] that have analyzed the gut microbiota of different types of GSDs, we found a strong reduction in intestinal microbiota richness and diversity compared with healthy controls and a dramatic increase in the phylum Proteobacteria.…”

“…in the patients' gut. Colonetti and coworkers [27] did not observe changes in Faecalibacterium and Oscillospira relative abundances in their dataset, and found Blautia spp., enriched in our cohort, to be depleted in GSD patients. These differences could be ascribable to the multiplicity of GSDs (type Ia/Ib, III, IX vs. type Ia/Ib), the use of antibiotics before sampling (10/24 subjects vs. 0/9), the sequencing method used (Ion Torrent vs. Illumina MiSeq) and the database used for OTU processing (SILVA vs. Greengenes).…”

Long Term Management of Glycogen Storage Disease Type 1b: A Brazilian Tertiary Center Experience

“…More studies are needed to first more broadly the changes in the composition of the gut microbiota in GSD 1b, and later identify whether there will be any specific indications for probiotics in this group of patients. A national study has reported dysbiosis in GSD (20) , and this finding was later corroborated in an Italian study (21) . As the knowledge in this area is still evolving, probiotics may be costly and are not routinely available in our public health system in Brazil, none of the patients in the present cohort used probiotics.…”

Bone Mineral Density in Patients with Hepatic Glycogen Storage Diseases

“…It is important to highlight that intestinal calcium absorption may be influenced by the gut microbiota [48][49][50]. Colonetti et al (2019) and Ceccarani et al (2020) described that patients with GSD presented intestinal dysbiosis and increased proinflammatory rate. This can indicate a higher risk for low BMD, which was not confirmed by our study [50][51][52].…”