Multi-omics analysis of pediatric short bowel syndrome induced intestinal failure and associated liver disease: Association with gut microbial deviations.
Mutanen A, Saqib S, et al. • Clinical nutrition (Edinburgh, Scotland) • 2026
Pediatric SBS-IF is characterized by distinct microbiota clusters linked to clinical phenotype and bile acid metabolism, highlighting contribution of gut-liver crosstalk to IFALD pathogenesis and providing avenues for early diagnostics.
Key Findings
Results
Pediatric SBS-IF patients showed markedly reduced richness and diversity of intestinal microbiota compared to healthy controls.
59 pediatric SBS-IF patients provided 177 fecal samples total
100 samples were collected during parenteral nutrition (PN) and 77 after weaning off PN
Gut microbiota was analyzed using 16S rRNA amplicon sequencing
Results were compared to healthy controls
Results
Unsupervised clustering on pathway abundances revealed five principal microbial clusters dominated by Escherichia, Klebsiella, Lactobacillus, Veillonella, and Faecalibacterium spp., each associated with different metabolic processes.
Clustering was based on sequence-based prediction of functional profiles
Each cluster was associated with distinct metabolic processes
Clusters were segregated by residual bowel length, serum citrulline, PN dependency, and intestinal anatomy
End-enterostomy was associated with the Klebsiella and Escherichia dominant clusters
Results
Faecalibacterium-dominant cluster predominated after achieving enteral autonomy, while PN dependency and short remaining bowel were linked to the Lactobacillus-dominant cluster.
Faecalibacterium predominated in 67% of samples after achieving enteral autonomy
PN dependency, short remaining bowel, and low citrulline levels were linked to the Lactobacillus-dominant cluster
Clusters were segregated by residual bowel length and PN dependency status
Intestinal anatomy (e.g., end-enterostomy) further differentiated cluster distribution
Results
The Lactobacillus-dominant cluster was characterized by overexpression of bile acid metabolism pathway genes and elevated serum unconjugated chenodeoxycholic acid.
Elevated serum unconjugated chenodeoxycholic acid was found in the Lactobacillus-dominant cluster
Unconjugated chenodeoxycholic acid correlated inversely with histological cholestasis (r = -0.435, P = 0.003)
Unconjugated chenodeoxycholic acid correlated inversely with portal inflammation (r = -0.507, P < 0.001)
Liver transcriptome was analyzed using bulk RNA sequencing of selected liver biopsies (n = 31)
Results
SBS-IF livers showed activation of bile acid metabolism including upregulation of CYP7A1, alongside increased serum C4.
CYP7A1, a key enzyme in bile acid synthesis, was among the activated genes
Serum bile acids were measured with mass spectrometry
Serum C4 (a marker of bile acid synthesis) was elevated
Liver transcriptome data were related to liver histopathology and clinical outcomes
Methods
Surrogates of intestinal integrity were measured by ELISA in a subset of patients.
ELISA-based surrogates of intestinal integrity were measured in n = 67 samples
These measurements were integrated with gut microbiota, liver transcriptome, and serum bile acid data in the multi-omics analysis
Results were related to liver histopathology and clinical outcomes
Results
Multi-omics integration of gut microbiota, liver transcriptomes, serum bile acids, intestinal integrity markers, and clinical data revealed associations between microbial clusters and gut-liver axis disruption in pediatric SBS-IF.
Study integrated 16S rRNA sequencing, bulk RNA sequencing of liver biopsies (n = 31), mass spectrometry-based serum bile acids, and ELISA-based intestinal integrity markers (n = 67)
59 patients with 177 fecal samples were included
Results were compared to healthy controls and related to liver histopathology
Findings highlight the contribution of gut-liver crosstalk to IFALD pathogenesis
What This Means
This research studied how the gut microbiome (the community of bacteria living in the intestine) interacts with liver health in children who have short bowel syndrome (SBS) — a condition where much of the small intestine is missing or removed, requiring intravenous nutrition. These children are at risk of a serious liver complication called intestinal failure-associated liver disease (IFALD). The researchers collected stool samples, liver tissue, and blood from 59 children and used advanced molecular techniques to analyze bacteria, liver gene activity, and bile acids (chemicals made by the liver to help digest fat) all together.
The study found that children with SBS had far fewer and less diverse gut bacteria than healthy children. The bacterial communities clustered into five distinct types dominated by different bacteria (Escherichia, Klebsiella, Lactobacillus, Veillonella, and Faecalibacterium). Which cluster a child fell into was strongly related to how much bowel they had left, whether they still needed intravenous nutrition, and the structure of their remaining intestine. Children who successfully transitioned to eating normally tended to have a Faecalibacterium-dominant microbiome, while those still dependent on intravenous nutrition with very short bowels tended to have a Lactobacillus-dominant microbiome. The Lactobacillus cluster was specifically associated with altered bile acid levels in the blood, and higher levels of one bile acid (unconjugated chenodeoxycholic acid) were linked to less liver inflammation and cholestasis (bile buildup in the liver).
This research suggests that specific patterns of gut bacteria in children with short bowel syndrome are closely tied to liver health and bile acid processing, and that monitoring these bacterial patterns could help identify children at higher risk for liver disease earlier. It also points to the gut-liver communication pathway as a potential target for future treatments or preventive strategies in this vulnerable patient population.
Mutanen A, Saqib S, de Vos W, Niemi M, Salonen A, Pakarinen M. (2026). Multi-omics analysis of pediatric short bowel syndrome induced intestinal failure and associated liver disease: Association with gut microbial deviations.. Clinical nutrition (Edinburgh, Scotland). https://doi.org/10.1016/j.clnu.2026.106660