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Alterations in gut microbiota and insights into the colonic function by clodronate: a study using short bowel syndrome rat model

  • 0Department of Pediatric Surgery, Medical and Dental Area, Research and Education Assembly, Research Field in Medical and Health Sciences, Kagoshima University, Kagoshima, Japan.
Pediatric Surgery International +

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August 18, 2025

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August 18, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Clodronate alters gut bacteria in short bowel syndrome (SBS) rats, potentially suppressing liver disease. However, high doses may negatively impact the colon barrier function.

Area Of Science

  • Gastroenterology
  • Microbiome research
  • Pharmacology

Background

  • Short bowel syndrome (SBS) can lead to intestinal failure-associated liver disease (IFALD).
  • Vesicular nucleotide transporter inhibitors, like clodronate, are being investigated for IFALD suppression.
  • The impact of clodronate on gut microbiota and colonic barrier in SBS requires further elucidation.

Purpose Of The Study

  • To investigate the effects of clodronate on gut microbiota and colonic barrier in a rat model of SBS.
  • To evaluate dose-dependent effects of clodronate on microbial community structure, colonic histology, and gene expression.

Main Methods

  • A 90% small bowel resection was performed on Sprague-Dawley rats to induce SBS.
  • Rats were randomized into control (SBS/TPN), low-dose clodronate (20 mg/kg/day), and high-dose clodronate (60 mg/kg/day) groups.
  • Fecal and colon samples were analyzed for gut microbiota composition, tight junction gene expression (Claudin-1), and inflammatory markers (NLRP3, IL-6).

Main Results

  • High-dose clodronate induced significant heterogeneity in bacterial community structure and decreased the Firmicutes/Bacteroidota ratio.
  • The distal colon crypt depth was significantly increased in the high-dose clodronate group.
  • Claudin-1 expression decreased in the proximal colon of the low-dose group, while NLRP3 and IL-6 expressions were significantly altered in the proximal colon across groups.

Conclusions

  • Clodronate significantly alters gut microbiota composition in an SBS rat model.
  • These microbial alterations may contribute to the suppression of IFALD.
  • Potential adverse effects on the colonic barrier warrant further investigation.

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