320.1: Changes in gut microbiota and its metabolic activity in pediatric intestinal failure patients receiving long-term parenteral nutrition

Abstract

Introduction: Our aim was to characterize the gut microbiota and its metabolic activity in children with IF compared with healthy controls and to explore associations with clinical parameters. Methods: Sixty-six serial fecal samples (median of 3 per patient) were collected from 15 IF patients (median age 4.3y) dependent on parenteral nutrition (PN) for a median of 3.6y. Single samples from 25 healthy controls were collected. Gut microbiota was characterized using 16S rRNA sequencing. Short-chain fatty acids (SCFA) were quantified with gas chromatography and D and L lactate using a modified enzymatic commercial essay. Results: At the first sample, IF patients had lower concentration of total SCFA (p=0.008), propionic and butyric acid (p<0.001), and higher D and L lactate than controls (p<0.001). Total bacterial load (16S rRNA gene copies/g) was lower in patients (p=0.003). Their microbial community was characterized by a lower α-diversity (Shannon index, p<0.001), taxon richness (number of distinct species, Chao richness, p=0.006) and evenness (a metric of species distribution, p<0.001) than controls (Figure 1). The microbial community structure of IF patients was distinct from that of controls (p=0.002) and presented a higher degree of dispersion (inter-individual variation). Surgical IF patients had lower α-diversity (p<0.001) than functional IF patients. Duration of PN was negatively associated with Chao richness (β=-0.29, p=0.04) and the percentage of calories provided by PN (%PN) was negatively associated with Shannon index (β=-0.33, p=0.02) and Chao richness (β=-0.34, p=0.02). Enteral fibre intake (g/kg) was positively associated with Shannon diversity (β=0.42, p<0.01). Duration of PN and %PN explained 5.5% and 6.3% of the variation in microbial community structure (p<0.01). The relative abundance of 110/200 most abundant genera was significantly different between patients and controls. Patients had higher abundance of Enterobacteriaceae, Lactobacillaceae and Staphylococcaceae, and lower abundance of Bacteroidaceae and Bifidobacteriaceae. Conclusion: The microbiota of pediatric IF patients is distinct to that of healthy controls with altered SCFA, lower bacterial diversity, loss of dominant microbial taxa and increased abundance of sub-dominant and potentially harmful species. Associations between microbial and PN associated characteristics offer the potential to use the gut microbiota as a biomarker to guide clinical practice during intestinal adaptation.