Inflammation, infections and the microbiome of children with short bowel syndrome
Theses
Overview
Overview
abstract
Children with short bowel syndrome have reduced gastrointestinal mass due to surgical resection in the neonatal period. This multi-pronged health translational study investigated the previous infectious history, microbiome, and inflammation of twelve children with this disease. We sought to further understand how dysbiosis, bacterial products such as butyrate, and intestinal permeability may link with the type and frequency of bloodstream infections and systemic inflammation.
The most frequent pathogens identified in bloodstream infections were coagulase-negative Staphylococcus, Enterococcus species, Klebsiella species and Candida species. Sixty-one percent of cultured microbes could be considered enteric with a gastrointestinal origin.
With high-thoroughput 16S rRNA fecal analysis, children with intestinal failure demonstrated the most significant dysbiosis with the lowest Shannon diversity and an abundance of the Escherichia genus seemingly attributable to the pro-inflammatory species E. coli. Commensal anaerobes known to produce SCFA including Ruminococcaceae and Lachnospiraceae were significantly reduced in those with IF. Similarly, measured butyric acid was significantly reduced in children with IF compared to controls (median 0.37nmol/mg vs 10.92nmol/mg; p<0.0001).
Serum analysis of intestinal permeability markers including circulating bacterial products lipopolysaccharide and muramyl dipeptide (MDP) were similar between children with SBS and controls. Furthermore, no differences were detected in gene expression of pro- or anti- inflammatory transcription factors, cytokine concentration, or fecal calprotectin.
Children with SBS exhibit dysbiosis, a reduction in SCFA-producing microbes and reduction in butyrate concentration. Fecal analysis has identified a significant abundance of likely E. coli however it remains the sixth most common microbe cultured in bloodstream infections. The microbial community is significantly altered in children with intestinal failure with implications on complications of this disease including feed advancement, bacterial overgrowth, gastrointestinal motility and infection. Further research will be needed to investigate if manipulation of the microbiome can influence important clinical outcomes and alter bacterial translocation and infection.
