The microbiome’s role in pediatric intestinal failure and associated liver disease

 Gray's anatomy schematic of the liver.

Gray's anatomy schematic of the liver.

On Wednesday we talked about children who suffer from short bowel syndrome (SBS), specifically highlighting the role of the gut microbiome alongside its relationship to parenteral nutrition (PN).  In addition to demonstrating microbial dysbiosis in children with SBS, intestinal dysbiosis was noticed in patients receiving PN, while those who had been weaned off showed bacterial overgrowth. 

SBS can also lead to intestinal failure (IF) and further complications.  Among the many, PN and disrupted bowel function have both been shown to lead to IF-associated liver disease (IFALD), which can result in severe illness and even death.  Steatosis, a pathological indication used to describe abnormal lipid retention in cells, has been observed in liver histological samples. 

The cause of IFALD remains unclear, but findings from studying other liver disorders suggest involvement of the gut microbiome.  Intestinal overgrowth has been postulated for quite some time now, but evidence is lacking and the exact biological underpinnings that lead to liver injury remain unclear.  Researchers in Finland sought to address this, estimating that IF-induced disruptions to the gut microbiome of pediatric patients played a direct role in causing this liver damage. 

Twenty-three pediatric patients developing IF were selected for this study.  Researchers collected fecal samples to analyze microbiota populations and took liver biopsies to examine inflammatory damage and fibrotic tissue morphology.  In line with previous findings, the microbiomes of patients with IF had limited bacterial diversity and species richness as compared to those of healthy children and adults. 

A strong correlation was observed between microbiota composition and liver steatosis, and different microbiota strains were shown to be associated with different stages of the disease progression.  Additionally, an overabundance of microbiota in the Proteobacteria phylum was observed in patients undergoing PN.  The Proteobacteria phylum contains many opportunistic pathogenic bacteria, including E. coli.  Interestingly, Proteobacteria species produce lipopolysaccharides, which are known toxins to the liver.  The researchers were also able to model that bacterial composition was a strong predictor of liver steatosis than nutrition history or bowel length post-resection surgery. 

These findings led the researchers to propose that intestinal resection, alongside PN, disrupts the intestines, and consequently native microbiota populations.  The disruption and species decline invites opportunistic bacteria, such as those in the Proteobacteria phylum, to populate the intestine.  These bacteria release of lipopolysaccharides into the blood stream, and upon reaching the liver, induce inflammatory toxic damage leading to steatosis. 

This study complements Wednesday’s discussion and helps us makes better sense of a convoluted disease complication that has drastic consequences.  Understanding the microbiome’s influence on post-SBS liver disease can help clinicians make informed decisions to rescue pediatric patients from these ailments.  

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