Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility

Kazuhiro Nishiyama, Kimiya Aono, Yasuyuki Fujimoto, Mitsuru Kuwamura, Toshiya Okada, Hayato Tokumoto, Takeshi Izawa, Ryoichi Okano, Hidemitsu Nakajima, Tadayoshi Takeuchi, Yasu Taka Azuma

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Organ–organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation. Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor-α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.

Original languageEnglish
Pages (from-to)6667-6678
Number of pages12
JournalJournal of cellular physiology
Volume234
Issue number5
DOIs
Publication statusPublished - May 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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