Functional Disorders: Slow-Transit Constipation

Tillou, John; Poylin, Vitaliy

doi:10.1055/s-0036-1593436

Cited by 42 publications

(31 citation statements)

References 96 publications

(190 reference statements)

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“…There are conflicting results regarding intestinal transit time both for IBS patients with constipation and for those with diarrhea probably reflecting the many different important regulatory factors affecting transit time and motility in the gut [ 11 , 28 – 30 ]. Prolonged CTT may be found in patients with slow transit constipation [ 31 ], but only a small range of patients with IBS-C has slow transit time [ 32 – 34 ].…”

Section: Discussionmentioning

confidence: 99%

Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation

et al. 2017

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IntroductionIncreased intestinal hydration by activation of the epithelial enzyme linked receptor guanylate cyclase C (GC-C) is a pharmacological principle for treating constipation. Activating mutations in the GUCY2C gene encoding GC-C cause Familial GUCY2C diarrhea syndrome (FGDS) which has been diagnosed with severe dysmotility.AimTo investigate gut motility and hormones before and after a meal in FGDS patients and compare with healthy controls (HC).Subjects and methodsBristol stool chart and stool frequency was assessed. Before and after a meal occlusive and non-occlusive contractions were obtained using ultrasound. A wireless motility capsule (WMC) recorded gut transit time, pH, contractions and pressure. Plasma levels of selected gut hormones were measured at different time points.ResultsThe FGDS patients had 4 (range 1–10) loose stools/day and prolonged total gut transit time compared to HC, 55.5 h vs 28.5 h, respectively,with significantly increased colon transit time. In FGDS patients, pH in duodenum, small bowel and colon was increased and the number of contractions and the intraluminal pressure were significantly decreased, measured by WMC. Ultrasound showed in small bowel increased number of non-occlusive contractions in the FGDS patients. Serotonin (5-HT) plasma levels in the HC peaked 30 min after the meal, while the FGDS patients had no response.ConclusionDespite having diarrhea, the FGDS patients have prolonged transit time through the gut compared to HC, particularly in colon. The reduced number of intestinal contractions and lack of 5-HT release after a meal in FGDS patients surprisingly resemble colonic motility disturbances seen in patients with constipation.

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Section: Discussionmentioning

confidence: 99%

Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation

et al. 2017

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“…[1][2][3][4][5][6][7][8] Delayed colonic transit time (CTT) is considered as one of the main etiological mechanisms of constipation. [9][10] Constipation is a common condition encountered in all clinical departments, and is known to markedly diminish activities of daily living and labor productivity and lessen the quality of life (QOL). Thus, it is a condition that should be treated quickly and appropriately.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Double-blind Placebo-controlled Trial on the Effect of Magnesium Oxide in Patients With Chronic Constipation

Mori

Tomita

Fujimura

et al. 2019

J Neurogastroenterol Motil

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Background/Aims Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. Methods We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. Results One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo (P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). Conclusion Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms.

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“…Previous studies show a loss of enteric neurons3 and interstitial cells of Cajal (ICC)—the pacemakers of the gut 4 5. However, in the majority of cases, a histological analysis is not diagnostic,6 which may suggest functional pathology at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

microRNA overexpression in slow transit constipation leads to reduced Na_V1.5 current and altered smooth muscle contractility

Mazzone

Strege

Gibbons

et al. 2019

Gut

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ObjectiveThis study was designed to evaluate the roles of microRNAs (miRNAs) in slow transit constipation (STC).DesignAll human tissue samples were from the muscularis externa of the colon. Expression of 372 miRNAs was examined in a discovery cohort of four patients with STC versus three age/sex-matched controls by a quantitative PCR array. Upregulated miRNAs were examined by quantitative reverse transcription qPCR (RT-qPCR) in a validation cohort of seven patients with STC and age/sex-matched controls. The effect of a highly differentially expressed miRNA on a custom human smooth muscle cell line was examined in vitro by RT-qPCR, electrophysiology, traction force microscopy, and ex vivo by lentiviral transduction in rat muscularis externa organotypic cultures.ResultsThe expression of 13 miRNAs was increased in STC samples. Of those miRNAs, four were predicted to target SCN5A, the gene that encodes the Na+ channel NaV1.5. The expression of SCN5A mRNA was decreased in STC samples. Let-7f significantly decreased Na+ current density in vitro in human smooth muscle cells. In rat muscularis externa organotypic cultures, overexpression of let-7f resulted in reduced frequency and amplitude of contraction.ConclusionsA small group of miRNAs is upregulated in STC, and many of these miRNAs target the SCN5A-encoded Na+ channel NaV1.5. Within this set, a novel NaV1.5 regulator, let-7f, resulted in decreased NaV1.5 expression, current density and reduced motility of GI smooth muscle. These results suggest NaV1.5 and miRNAs as novel diagnostic and potential therapeutic targets in STC.

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Functional Disorders: Slow-Transit Constipation

Cited by 42 publications

References 96 publications

Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation

Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation

A Randomized Double-blind Placebo-controlled Trial on the Effect of Magnesium Oxide in Patients With Chronic Constipation

microRNA overexpression in slow transit constipation leads to reduced Na_V1.5 current and altered smooth muscle contractility

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Functional Disorders: Slow-Transit Constipation

Cited by 42 publications

References 96 publications

Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation

Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation

A Randomized Double-blind Placebo-controlled Trial on the Effect of Magnesium Oxide in Patients With Chronic Constipation

microRNA overexpression in slow transit constipation leads to reduced NaV1.5 current and altered smooth muscle contractility

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microRNA overexpression in slow transit constipation leads to reduced Na_V1.5 current and altered smooth muscle contractility