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Introduction <p>Previous research suggests that clodronate, a vesicular nucleotide transporter inhibitor, may suppress intestinal failure-associated liver disease (IFALD) in short bowel syndrome (SBS). The present study investigated the effects of clodronate on the gut microbiota and colonic barrier in SBS rat model.</p> Purpose <p>Sprague–Dawley rats underwent 90% small bowel resection and then were randomized into three groups (<i>n</i> = 8 each): SBS/TPN (Control), SBS/TPN with low-dose clodronate (Low, 20&#xa0;mg/kg/day), and SBS/TPN with high-dose clodronate (High, 60&#xa0;mg/kg/day). After 7 days, fecal and colon samples were collected to analyze the gut microbiota, histological findings, gene expression of tight junction, and inflammatory markers.</p> Results <p>While alpha diversity showed no significant differences between the groups, high-dose clodronate-induced heterogeneity in the bacterial community structure. At the phylum level, the Firmicutes/Bacteroidota ratio significantly decreased in the High group. The crypt depth at distal colon was significantly deepest in the High group (<i>p</i> = 0.01). The Claudin-1 expression decreased significantly in the Low group in proximal colon (<i>p</i> = 0.019). The NLRP3 and IL-6 expressions in proximal colon showed significant differences among the groups (NLRP3: <i>p</i> &lt; 0.001, IL-6: <i>p</i> = 0.021).</p> Conclusion <p>Clodronate-induced alterations in the gut microbiota may contribute to IFALD suppression, albeit with potentially adverse effects on the colonic barrier.</p>

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

  • 期刊论文

  • 发表日期：

    2025年8月18日

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  • Ayaka Nagano,
  • Yudai Tsuruno,
  • Koshiro Sugita,
  • Shun Onishi,
  • Yumiko Tabata,
  • Chihiro Kedoin,
  • Masakazu Murakami,
  • Keisuke Yano,
  • Toshio Harumatsu,
  • Takafumi Kawano,
  • Nao Hasuzawa,
  • Masatoshi Nomura,
  • Tatsuru Kaji,
  • Satoshi Ieiri

摘要

Introduction

Previous research suggests that clodronate, a vesicular nucleotide transporter inhibitor, may suppress intestinal failure-associated liver disease (IFALD) in short bowel syndrome (SBS). The present study investigated the effects of clodronate on the gut microbiota and colonic barrier in SBS rat model.

Purpose

Sprague–Dawley rats underwent 90% small bowel resection and then were randomized into three groups (n = 8 each): SBS/TPN (Control), SBS/TPN with low-dose clodronate (Low, 20 mg/kg/day), and SBS/TPN with high-dose clodronate (High, 60 mg/kg/day). After 7 days, fecal and colon samples were collected to analyze the gut microbiota, histological findings, gene expression of tight junction, and inflammatory markers.

Results

While alpha diversity showed no significant differences between the groups, high-dose clodronate-induced heterogeneity in the bacterial community structure. At the phylum level, the Firmicutes/Bacteroidota ratio significantly decreased in the High group. The crypt depth at distal colon was significantly deepest in the High group (p = 0.01). The Claudin-1 expression decreased significantly in the Low group in proximal colon (p = 0.019). The NLRP3 and IL-6 expressions in proximal colon showed significant differences among the groups (NLRP3: p < 0.001, IL-6: p = 0.021).

Conclusion

Clodronate-induced alterations in the gut microbiota may contribute to IFALD suppression, albeit with potentially adverse effects on the colonic barrier.