Multi-kingdom gut microbiota analyses revealed type-specific microbial signatures across three anatomical types of pediatric short bowel syndrome, with SBS I enriched in pathogens, SBS II depleted of beneficial SCFA-producing species, and SBS III characterized by loss of bile acid-metabolizing microbes and Lactobacillus expansion, identifying ileocecal valve loss as the primary determinant of SBS I microbial profiles.
Key Findings
Results
Children with SBS exhibited a significant reduction in alpha-diversity compared with healthy controls, with no significant difference in alpha-diversity observed among the three SBS types.
Study included 26 healthy controls and 34 pediatric SBS patients across three anatomical types: 8 SBS I, 15 SBS II, and 11 SBS III.
Deep shotgun metagenomic sequencing of fecal samples was used with modified DNA extraction to capture all four kingdoms.
Alpha-diversity was significantly reduced in SBS patients as a group relative to controls, but did not differ significantly between SBS subtypes.
Results
The proportion of archaea was significantly decreased in all SBS types compared with controls, while bacteria, fungi, and viruses remained similar across types.
This finding was consistent across all three anatomical SBS types (SBS I, II, and III).
Bacterial, fungal, and viral kingdoms did not show significant differences in proportional abundance among SBS types relative to controls.
Multi-kingdom characterization included bacteria, fungi, archaea, and viruses using modified DNA extraction and deep shotgun metagenomic sequencing.
Results
SBS I was enriched with pathogenic bacteria, particularly species from the Streptococcus and Klebsiella genera.
SBS I represents one of three anatomical subtypes defined in the study cohort (n=8 patients).
Enrichment of these pathogens was identified as a type-specific microbial signature distinct from SBS II and SBS III.
Ecological network disruption was described as most pronounced in SBS I compared to the other SBS types.
Results
SBS II was characterized by a depletion of beneficial short-chain fatty acid (SCFA)-producing species, including Faecalibacterium prausnitzii.
SBS II cohort comprised 15 patients, the largest of the three SBS subgroups.
Faecalibacterium prausnitzii was specifically named as a depleted beneficial species in SBS II.
The depletion of SCFA-producing species was identified as a distinct microbial signature specific to SBS II relative to other SBS types and controls.
Results
SBS III displayed loss of bile acid-metabolizing species alongside a significant expansion of Lactobacillus species.
SBS III cohort comprised 11 patients.
The combination of bile acid-metabolizing species loss and Lactobacillus expansion was identified as the type-specific signature for SBS III.
This pattern was distinct from the pathogen enrichment seen in SBS I and the SCFA-producer depletion seen in SBS II.
Results
Core metabolic pathways were markedly suppressed in SBS I compared with controls.
Functional analysis using metagenomic data revealed pathway-level suppression specific to SBS I.
This suppression was more pronounced in SBS I than in the other SBS types.
Functional pathway disruption in SBS I was linked to the distinct microbial community composition including pathogen enrichment.
Results
Ecological networks were rewired in SBS overall, with the most pronounced disruption observed in SBS I.
Network rewiring was identified across SBS types but showed differential severity.
SBS I exhibited the most disrupted microbial ecological network architecture compared with SBS II, SBS III, and controls.
Network analysis was conducted as part of the multi-kingdom microbial characterization.
Results
Ileocecal valve loss was identified as the primary determinant of SBS I microbial profiles, linking it to impaired secretory functions and hepatic injury.
Integrated correlation analyses were used to identify anatomical determinants of microbial gene profiles.
Loss of the ileocecal valve was specifically associated with the microbial community structure observed in SBS I.
Ileocecal valve loss was linked to both impaired secretory functions and hepatic (liver) injury in SBS I patients.
Methods
Modified DNA extraction combined with deep shotgun metagenomic sequencing successfully characterized the four-kingdom gut microbiota in pediatric SBS fecal samples.
The four kingdoms characterized were bacteria, fungi, archaea, and viruses.
Prior research in SBS gut microbiota had focused almost exclusively on bacteria, making this a methodological advance for this population.
The method was applied to fecal samples from 60 total participants (26 controls and 34 SBS patients).
What This Means
This research suggests that children with short bowel syndrome (SBS) — a serious condition where a significant portion of the intestine is missing or has been removed — have distinctly disrupted gut microbial communities compared to healthy children. Using advanced genetic sequencing techniques on stool samples, scientists examined not just bacteria but also fungi, archaea, and viruses in the guts of 34 children with three different anatomical types of SBS and 26 healthy children. The overall diversity of gut microbes was lower in all SBS patients, and the proportion of archaea (a type of single-celled organism) was specifically reduced across all SBS types.
Importantly, the research found that each of the three anatomical types of SBS had its own distinct microbial pattern. Children with SBS type I had more harmful bacteria (pathogens like Streptococcus and Klebsiella) and suppressed metabolic functions in their gut microbiome, which was linked to the loss of a specific intestinal valve called the ileocecal valve. This valve loss was also associated with liver injury. Children with SBS type II had fewer beneficial bacteria that produce short-chain fatty acids — molecules important for gut health. Children with SBS type III had lost bacteria that help process bile acids and had unusually high levels of Lactobacillus bacteria.
This research suggests that SBS is not a single condition from a microbiome perspective, and that each anatomical subtype may need different approaches to treatment. Understanding these specific microbial patterns could help doctors develop more targeted therapies — such as personalized probiotics or dietary interventions — to support children living with different forms of SBS and improve their long-term health outcomes.
Wu Q, Li C, Chen S, Xu J, Yan W, Lu L, et al.. (2026). Multi-kingdom gut microbiota analyses identify biomarkers of different types of pediatric short bowel syndrome.. mSystems. https://doi.org/10.1128/msystems.00316-26