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

Abstract

BackgroundThis 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. MethodsSerial 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. ResultsThe 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 (R 2 =6%, p=0.005), % of calories from PN (R 2 =6%, p=0.005) and fiber intake (R 2 =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.

Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders

“…Taken together, these changes result in a loss of the overall barrier function and subsequent bacterial translocation [ 158 ]. Moreover, there is also growing evidence showing that gut mucosal atrophy is driven by TPN-related gut microbiota dysbiosis, characterized by a decreased α-diversity, a lower abundance of Firmicutes as well as an increased prevalence of potentially pathogenic Gram-negative bacteria, mainly belonging to Proteobacteria phylum [ 1 , 16 , 159 , 160 , 161 ]. Interestingly, the studies carried out to date also suggest that these changes in bacterial diversity and richness are positively related to the longer duration of parenteral nutrition and its related consequences, such as the lack of fermentable fiber and the depletion of beneficial SCFAs, further increasing the abundance of potentially harmful bacteria [ 16 , 159 , 161 , 162 ].…”

“…Moreover, there is also growing evidence showing that gut mucosal atrophy is driven by TPN-related gut microbiota dysbiosis, characterized by a decreased α-diversity, a lower abundance of Firmicutes as well as an increased prevalence of potentially pathogenic Gram-negative bacteria, mainly belonging to Proteobacteria phylum [ 1 , 16 , 159 , 160 , 161 ]. Interestingly, the studies carried out to date also suggest that these changes in bacterial diversity and richness are positively related to the longer duration of parenteral nutrition and its related consequences, such as the lack of fermentable fiber and the depletion of beneficial SCFAs, further increasing the abundance of potentially harmful bacteria [ 16 , 159 , 161 , 162 ]. This TPN-related shift in the gut microbiota’s composition is strongly suspected to trigger a TLR-dependent proinflammatory response in the gut with the consequence being a loss in the epithelial integrity, thus causing morphological alterations, and a loss in the barrier function [ 1 ].…”

“…Potent interventions to manipulate the gut microbiome include the use of pharmacological doses of SCFAs, prebiotics, probiotics, antibiotics and a fecal transplantation. SCFAs such as acetate, propionate and butyrate have the ability to promote cell proliferation and the differentiation of colonocytes, prevent the growth of opportunistic pathogens and are key regulators of the immune response [ 161 , 177 ]. Moreover, it might also be beneficial to use SCFAs as a trophic factor to stimulate and promote intestinal adaptation.…”

“…Limited evidence suggests that synbiotics may increase the fecal levels of SCFAs as well as Bifidobacteria , total facultative anaerobic bacteria, Enterobacteriaceae and Lactobacilli ; however, cases of bacteremia with prescribed probiotic bacteria in infants with SBS have also been reported. The efficacy of probiotics to promote an intestinal adaptation in patients with SBS is emerging, but evidence of their benefits remains limited; thus, the routine use of probiotics is currently not recommended in clinical practice [ 161 , 177 ]. Some studies have showed a reduction in pathogenic overgrowth and an improved growth and nutrition status in SBS patients treated with probiotics and/or synbiotics, although other researchers found no consistent positive or adverse effects of probiotics [ 194 ].…”

“…In summary, patients with SBS and/or IF have an altered gut microbiome and altered metabolic activity [ 161 ]. Despite differences in the primary pathology and underlying disease, the pattern of gut microbiota dysbiosis is very similar with profound shifts with an increase in Proteobacteria , especially Enterobacteriaceae , and a decrease in Bacteroidetes and often Firmicutes.…”