Gut microbiota and its diet-related activity in children with intestinal failure on long-term parenteral nutrition

BACKGROUND This study characterized the gut microbiota and its diet-related metabolic activity in children with intestinal failure (IF) on parenteral nutrition (PN) compared with healthy controls and in relation to disease characteristics. METHODS Serial fecal samples were collected from 15 IF patients (n = 68) and from 25 healthy children (n = 25). The fecal microbiota, and short chain fatty acids (SCFA) were measured. RESULTS The microbiota of patients with IF had a lower bacterial load (p = 0.003), Shannon diversity index (p<0.001), taxon evenness (p<0.001) and richness (p = 0.006) than healthy controls. Patients with surgical IF had lower α-diversity (p<0.039) than those with functional IF. Patients with IF had less propionic and butyric acid (p<0.001), and more D and L-lactate than healthy controls (p<0.001). The percentage of calories supplied by PN (%PN) was negatively associated with microbiota diversity and influenced SCFA profile. IF patients had more Escherichia-Shigella (p = 0.006), Cronobacter (p = 0.001) and Staphylococcus (OTU 14, p<0.001) and less Faecalibacterium (p<0.001) and Ruminococcus 1 and 2 (p<0.001). Duration of PN (R2 = 6%, p = 0.005), % of calories from PN (R2 = 6%, p = 0.005) and fiber intake (R2 = 5%, p = 0.011) were predictive of microbiota community structure. A higher intake of enteral nutrition was associated with a microbiota composition and function closer to that of the healthy status. CONCLUSIONS The microbiota composition and its diet-related function are altered in pediatric IF, with profound depletion of beneficial SCFA and species, and supraphysiological increase of potentially harmful pathobionts. The influence of this compositional and functional microbial dysbiosis on patients' clinical outcomes and management warrants further exploration. This article is protected by copyright. All rights reserved.