Abstract
Background
Gastrointestinal motility is easily influenced by body condition. High-fat diet delayed intestinal transit in mice though enteric neuronal damage. Type 1 diabetic patients have often disruption of intestinal motility. Parkinson's disease shows gastrointestinal dysfunction.
It has also been reported that segmental and total colonic transit times were longer in patient on hemodialysis or peritoneal dialysis than in the general population. However, the mechanism of intestinal motility dysregulation in patients with kidney disease remains unclear. In this study, we investigated the mechanisms of intestinal motility dysregulation caused by renal impairment.
Methods
To investigate effect of renal impairment on intestinal motility, we examined the responses to electric field stimulation (EFS) in the longitudinal muscle obtained from the distal colon in 5/6 Nephrectomy mice (5/6 Nx) and sham operated mice (sham). Next, to determine the mechanisms of intestinal motility dysregulation, we measured expression levels of inflammatory cytokines in distal colon and we investigated populations of bacteria in stool. In addition, to reveal whether microbiota contribute to intestinal motility dysfunction in 5/6 Nx, we investigated the responses in the distal colon with antibiotic treatment. At last, we investigated whether uremic toxin is involved in inflammation by using RAW264.7 macrophage cell line.
Results
In the distal colon, magnitudes of EFS induced-relaxation were smaller in 5/6 Nx, compared with sham. The expression of IL-6, TNFα, and iNOS were increased in 5/6 Nx. Lactobacillus spices and Fusobacterium spices were decreased in stool of 5/6 Nx.
The magnitudes of EFS-induced relaxation in distal colon obtained from 5/6 Nx with antibiotic treatment were similar to those observed in sham with antibiotic treatment. Indole sulfate and trans-aconite acid enhanced LPS-induced TNFα production in RAW264.7 macrophage.
Conclusions
In this study, we investigated the mechanisms of intestinal motility dysregulation caused by renal impairment. In distal colon, renal impairment-induced change of microbiota and uremic toxin such as indoxyl sulfate and trans-aconite acid could contribute to inflammation which induced motility dysregulation. Thus, microbiota and uremic toxin contribute to intestinal motility dysregulation induced by renal impairment.
