Association between fecal short-chain fatty acid levels and constipation severity in subjects with slow transit constipation.

OBJECTIVE: We measured the fecal levels of short-chain fatty acids (SCFAs) in subjects with slow transit constipation (STC) and assessed the correlation between SCFA levels and disease severity as well as quality of life. METHODS: We isolated the supernatant from fecal samples of healthy and STC subjects and measured the SCFA levels. To assess the correlation between fecal SCFA levels and disease severity as well as quality of life, we used the Constipation Scoring System, Patient Assessment of Constipation Symptoms, and Patient Assessment of Constipation Quality of Life questionnaires. RESULTS: 16 STC subjects and 16 healthy controls were enrolled. STC subjects had lower SCFA levels, but the difference was not statistically significant (475.85 ±â€…251.68 vs. 639.77 ±â€…213.97 µg/ml, P = 0.056). Additionally, STC subjects had lower acetic and propionic acid levels (149.06 ±â€…88.54 vs. 261.33 ±â€…109.75 µg/ml and 100.60 ±â€…60.62 vs. 157.34 ±â€…66.37 µg/ml, respectively, P < 0.05) and higher isobutyric and isovaleric acid levels (27.21 ±â€…15.06 vs. 18.16 ±â€…8.65 µg/ml and 31.78 ±â€…18.81 vs. 16.90 ±â€…10.05 µg/ml, respectively, P < 0.05). At 252.21 µg/ml acetic acid, the specificity and sensitivity to distinguish healthy from STC subjects were 93.7% and 56.3%, respectively. In STC subjects, there were significant negative correlations between acetic and propionic acid levels and Constipation Scoring System scores. CONCLUSION: Fecal SCFA, acetic acid, and propionic acid levels decreased in STC subjects. There were significant negative correlations between the levels of the two acids and constipation severity.

Estrogen increases the expression of BKCa and impairs the contraction of colon smooth muscle via upregulation of sphingosine kinase 1.

Estrogen (E2) may impair the contraction of colonic smooth muscle (SM) leading to constipation. Large conductance Ca2+ -activated K+ channels (BKCa ) are widely expressed in the smooth muscle cells (SMCs) contributing to hyperpolarization and relaxation of SMCs. Sphingosine kinase 1 (SphK1) is known to influence the expression of BKCa . We aimed to elucidate the potential underlying molecular mechanism of BKCa and SphK1 that may influence E2-induced colonic dysmotility. In ovariectomized rats, SM contraction and expression of BKCa , SphK1, sphingosine-1-phosphate receptor (S1PR) were analyzed after the treatment with vehicle, BSA-E2, E2, and E2 receptor antagonist. The role of BKCa , SphK1, and S1PR in E2-induced SM dysmotility was investigated in rat colonic SMCs. The effect of SphK1 on SM contraction as well as on the expression of BKCa and S1PR was analyzed in SphK1 knock-out mutant mice and wild-type (WT) mice treated with or without E2. The E2-treated group exhibited a weak contraction of colonic SM and a delayed colonic transit. The treatment with E2 significantly upregulated the expression of BKCa , SphK1, S1PR1, and S1PR2, but not S1PR3, in colon SM and SMCs. Inhibition of BKCa , SphK1, S1PR1, and S1PR2 expression attenuated the effect of E2 on Ca2+ mobilization in rat colon SMCs. WT mice treated with E2 showed impaired gastrointestinal motility and enhanced expression of BKCa , S1PR1, and S1PR2 compared with those without E2 treatment. Conversely, in SphK1 knock-out mice treated with E2, these effects were partially reversed. E2 increased the release of S1P which in turn could have activated S1PR1 and S1PR2. Loss of SphK1 attenuated the effect of E2 on the upregulation of S1PR1 and S1PR2 expression. These findings indicated that E2 impaired the contraction of colon SM through activation of BKCa via the upregulation of SphK1 and the release of S1P. In the E2-induced BKCa upregulation, S1PR1 and S1PR2 might also be involved. These results may provide further insights into a therapeutic target and optional treatment approaches for patients with constipation.