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Background <p>This study aimed to investigate the effects of melatonin on diarrhea and visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and to explore its potential mechanisms through modulation of the TLR4/MyD88/NF-κB pathway.</p> Methods <p>Adult male Sprague-Dawley (SD) rats were used to establish an IBS-D model through a combination of chronic and acute stress. The rats were randomly divided into four groups: healthy control (HC), IBS-D, IBS-D + melatonin 5&#xa0;mg/kg (M-L), and IBS-D + melatonin 10&#xa0;mg/kg (M-H), with six rats in each group. Visceral sensitivity was assessed using the abdominal withdrawal reflex (AWR). The expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Western blotting and immunohistochemistry were employed to detect the expression of TLR4, MyD88, and NF-κB proteins in colon tissue. Additionally, 16&#xa0;S rRNA sequencing was used to analyze the composition of the intestinal microbiota.</p> Results <p>Compared to the HC group, the IBS-D group exhibited colonic inflammatory injury, increased AWR scores, elevated levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in the colon, and altered intestinal microbiota composition. Melatonin treatment reduced colonic inflammatory injury, decreased AWR scores, and lowered the levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in a dose-dependent manner. The intestinal microbiota composition in melatonin-treated groups showed a trend towards that of the HC group.</p> Conclusion <p>Melatonin improved diarrhea and visceral hypersensitivity in IBS-D rats, potentially through the modulation of the TLR4/MyD88/NF-κB pathway and partial restoration of the intestinal microbiota.</p>

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Melatonin alleviates diarrhea and visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome by modulating of the TLR4/MyD88/NF-κB pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月9日

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  • Zuohui Yuan,
  • Xiaoping Yang,
  • Xiaochun Wang,
  • Xinlong Shi,
  • Jia Chen,
  • Lijun Huang,
  • Jie Yang,
  • Yuping Shi,
  • Liping Zhang,
  • Ping Mai

摘要

Background

This study aimed to investigate the effects of melatonin on diarrhea and visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and to explore its potential mechanisms through modulation of the TLR4/MyD88/NF-κB pathway.

Methods

Adult male Sprague-Dawley (SD) rats were used to establish an IBS-D model through a combination of chronic and acute stress. The rats were randomly divided into four groups: healthy control (HC), IBS-D, IBS-D + melatonin 5 mg/kg (M-L), and IBS-D + melatonin 10 mg/kg (M-H), with six rats in each group. Visceral sensitivity was assessed using the abdominal withdrawal reflex (AWR). The expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Western blotting and immunohistochemistry were employed to detect the expression of TLR4, MyD88, and NF-κB proteins in colon tissue. Additionally, 16 S rRNA sequencing was used to analyze the composition of the intestinal microbiota.

Results

Compared to the HC group, the IBS-D group exhibited colonic inflammatory injury, increased AWR scores, elevated levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in the colon, and altered intestinal microbiota composition. Melatonin treatment reduced colonic inflammatory injury, decreased AWR scores, and lowered the levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in a dose-dependent manner. The intestinal microbiota composition in melatonin-treated groups showed a trend towards that of the HC group.

Conclusion

Melatonin improved diarrhea and visceral hypersensitivity in IBS-D rats, potentially through the modulation of the TLR4/MyD88/NF-κB pathway and partial restoration of the intestinal microbiota.