SBS-IF-CiC features an immature distal gut microbiota and apraglutide promotes early ecological maturation, suggesting that combining GLP-2 analog therapy with microbiome-targeted strategies may further enhance intestinal and ecosystem adaptation.
Key Findings
Results
Patients with SBS-IF-CiC exhibited an altered gut ecosystem characterized by reduced microbial richness and loss of colonic anaerobes compared to controls.
The study enrolled 9 adults with SBS-IF-CiC (Leuven n=7, Paris n=2) in a 52-week multicenter, open-label, phase 2 study
Baseline comparison used duodenal and sigmoid colonic biopsies from 20 controls (10 per region)
SBS patients showed dominance of Lactobacillus and Bifidobacterium with larger inter-subject variability
Patients had lower fecal pH, higher moisture, and lower microbial load compared to controls
The microbiota pattern was described as characteristic of an 'immature distal gut microbiota'
Results
Apraglutide did not change overall microbial diversity or stool parameters over the 52-week treatment period.
Weekly subcutaneous apraglutide was administered over 52 weeks
Analyses included mucosa-associated and fecal microbiota, fecal parameters, and fermentation metabolites
Overall diversity metrics remained unchanged despite treatment
Stool parameters including pH, moisture, and microbial load were not significantly altered by apraglutide
Results
Apraglutide reduced inter-subject variability in both stool and sigmoid colon microbiota.
Reduction in inter-subject variability was observed in stool samples
Reduction in inter-subject variability was also observed in sigmoid colon samples
This reduction in variability was interpreted as a sign of 'early ecological maturation'
The effect on variability was noted without corresponding changes in overall diversity metrics
Results
Bifidobacterium decreased in both stool and sigmoid colon following apraglutide treatment, while Prevotella increased in stool from some patients.
Bifidobacterium, one of the dominant taxa at baseline, was reduced in stool samples during treatment
Bifidobacterium reduction was also observed in sigmoid colon mucosal biopsies
Prevotella increased in stool from some patients, suggesting heterogeneous microbiota responses
Lactobacillus remained dominant throughout the treatment period despite these changes
These shifts were interpreted as movement toward a more mature microbiota composition
Results
Specific microbial taxa correlated with fecal butyrate, propionate, and reduced distal colonic motility, indicating microbial metabolism may support intestinal adaptation.
Correlations were identified between specific taxa and fecal fermentation metabolites including butyrate and propionate
Correlations were also found between specific taxa and reduced distal colonic motility
These associations suggest microbial metabolic activity may contribute to the intestinal adaptation process boosted by apraglutide
Duodenal, distal small bowel, and sigmoid colon biopsies as well as fecal and plasma samples were collected and analyzed over time
Background
The rapid transit and increased oxygen in the gut of SBS-CiC patients reshaped the microbiota prior to treatment, creating a distinct baseline ecosystem.
SBS with colon-in-continuity (CiC) is characterized by rapid transit and increased oxygen that reshapes gut microbiota
This environment promotes oxygen-tolerant organisms such as Lactobacillus and Bifidobacterium over strict anaerobes
The altered ecosystem featured reduced richness and loss of colonic anaerobes
Larger inter-subject variability at baseline distinguished SBS patients from healthy controls
Discussion
The authors propose that combining GLP-2 analog therapy with microbiome-targeted strategies may further enhance intestinal and ecosystem adaptation in SBS-IF-CiC.
This recommendation is based on apraglutide's observed promotion of early ecological maturation
The persistence of Lactobacillus dominance suggests that microbiome-targeted interventions may be needed to achieve fuller microbial normalization
The study was a phase 2 open-label trial (ClinicalTrials.gov NCT04964986) with a small sample size of 9 patients
The combination approach is presented as a hypothesis for future investigation rather than a tested intervention
What This Means
This research suggests that people with short bowel syndrome who still have part of their colon (a condition called SBS with colon-in-continuity) have a significantly altered gut microbiome compared to healthy individuals. Their gut bacteria show reduced diversity, a loss of oxygen-sensitive bacteria that are normally dominant in the colon, and an overgrowth of bacteria like Lactobacillus and Bifidobacterium that are more commonly seen in the small intestine or in infants. The gut environment in these patients — characterized by faster transit, lower acidity, and higher water content — appears to reshape which bacteria can survive there.
When patients were treated for 52 weeks with apraglutide, a new long-acting version of a hormone called GLP-2 that helps the intestine absorb more nutrients, the overall diversity of gut bacteria did not change dramatically. However, the treatment reduced the differences between patients (inter-subject variability) in the colon, and specific bacteria such as Bifidobacterium decreased while others like Prevotella increased in some patients. These shifts, along with correlations between certain bacteria and beneficial metabolites like butyrate and propionate, suggest the microbiome may be moving toward a more mature, adult-like state — a process the researchers call 'early ecological maturation.'
This research suggests that while apraglutide helps the intestine adapt and may nudge the gut microbiome toward healthier patterns, it does not fully normalize the bacterial community on its own. The findings open the door to the idea that combining GLP-2 therapy with treatments specifically targeting the microbiome — such as probiotics, prebiotics, or other interventions — could potentially improve outcomes for people with this serious condition that requires long-term intravenous nutrition.
Ekhlas D, Verbiest A, Stas M, De Meyere L, Vandermeulen G, Tóth J, et al.. (2026). Early ecological changes in intestinal microbiota with the long-acting GLP-2 analog apraglutide in short bowel syndrome.. Clinical nutrition ESPEN. https://doi.org/10.1016/j.clnesp.2026.103138