ABSTRACT
Background:
Symptoms of
irritable bowel syndrome with
diarrhea (IBS-D) are known to be influenced by circadian oscillation; however, the pathophysiological mechanism is still unclear.
Aims:
To investigate the
role and underlying mechanism of
colon circadian clock gene Bmal1 involved in the occurrence of symptoms in IBS-D
patients.
Methods:
Forty-six
patients with IBS-D and 34 normal controls from Army Medical Center of PLA during September 2018 to February 2021 were recruited in this study. IBS-severity scoring system (IBS-SSS) was used to evaluate the severity of IBS-D symptoms. A
colonoscopy was performed to obtain
biopsy specimens from rectosigmoid
colon. The concentration of
5-hydroxytryptamine (
5-HT), and expressions of Bmal1 and
chromogranin A (CgA), a
biomarker of
enterochromaffin cells (EC
cells), in colonic
mucosa were detected by
ELISA and double-labeled
immunofluorescence, respectively.
Results:
Both the
5-HT concentration and number of EC
cells in colonic
mucosa of IBS-D
patients were significantly higher than those of the normal controls (all P< 0.05). Bmal1 was mainly expressed in intestinal
epithelial cells and was highly expressed in EC
cells. Co-expression of Bmal1 and CgA was observed. Compared with the normal
control group biopsied at the same
time point, expression of Bmal1 was significantly higher in specimens taken at 9 a.m., and expression of Bmal1 was significantly lower in specimens taken at 17 p.m. in IBS-D
patients (all P< 0.05). Spearman correlation coefficient
analysis showed that Bmal1 expression at 9 a.m. was positively correlated with the total score of IBS-SSS and subscore of
abdominal pain and discomfort (r