Modern Management of Irritable Bowel Syndrome: More Than Motility

Abstract

In the treatment of irritable bowel syndrome (IBS), loperamide seems efficacious for diarrhea and ispaghula for constipation, while musculotropic spasmolytics may relieve abdominal pain. Antidepressants were found to be efficacious for abdominal pain, but their tolerance may be problematic and the therapeutic effect varied largely between trials. While meta-analyses suggest efficacy of probiotics as a group, the quality of the trials is often suboptimal and there is large variability. Lubiprostone, a chloride channel activator, and linaclotide, a guanylyl cyclase-C agonist, showed favorable effects on multiple symptoms in IBS with constipation. For IBS with diarrhea (IBS-D), the 5-HT₃ receptor antagonist ramosetron showed efficacy in men and women, but is currently only approved in Japan. A multicenter study with the anti-emetic 5-HT₃ receptor antagonist ondansetron showed efficacy on stool pattern in IBS-D. The poorly absorbable antibiotic rifaximin and eluxadoline, a mu opioid receptor agonist and delta antagonist, both showed efficacy in phase III trials in IBS-D and were approved by the FDA. Eluxadoline was associated with increased occurrence of sphincter of Oddi spasm and biliary pancreatitis. The non-pharmacological treatment of IBS, with dietary interventions (mainly gluten elimination and low FODMAP (fructose, oligo-, di-, monosaccharides and polyols)) has received a lot of attention lately. While responder rates vary across studies, perhaps based on regional variations in dietary intake of FODMAPs, the dietary approach seems to have acquired recognition as a valid therapeutic alternative. Long-term studies and comparative studies with pharmacotherapy, as well as elucidation of the underlying mechanisms of action, are needed.

Long‐term impact of the low‐FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome

“…In summary, we report that the low‐FODMAP diet is an effective long‐term strategy for the management of IBS addressing an area which has, to date, been largely unexplored …”

Efficacy and Safety of Probiotics in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis

“…The risk of bias was shown in Figure 2 and Figure 3. Twenty-three studies did not describe the details of the sequence generation process (Nobaek et al, 2000;Niedzielin et al, 2001;Niv et al, 2005;Simren and Lindh, 2006;Whorwell et al, 2006;Guyonnet et al, 2007;Enck et al, 2008;Zeng et al, 2008;Agrawal et al, 2009;Enck et al, 2009;Williams et al, 2009;Cui and Hu, 2012; Dapoigny et al, 2012;Charbonneau et al, 2013;Jafari et al, 2014;Ludidi et al, 2014;Pedersen et al, 2014;Sisson et al, 2014;Faghihi et al, 2015;Thijssen et al, 2016;Kim et al, 2018;Preston et al, 2018;Sun et al, 2018), and 35 studies did not describe the method of allocation concealment (Gade and Thorn, 1989;Nobaek et al, 2000;Niedzielin et al, 2001;Kajander et al, 2005;Niv et al, 2005;O'Mahony et al, 2005;Kim et al, 2006;Simren and Lindh, 2006;Whorwell et al, 2006;Guyonnet et al, 2007;Enck et al, 2008;Zeng et al, 2008;Agrawal et al, 2009;Enck et al, 2009;Williams et al, 2009;Choi et al, 2011;…”

“…Thirty-five RCTs (Gade and Thorn, 1989;Nobaek et al, 2000;Niedzielin et al, 2001;Kim et al, 2003;Kajander et al, 2005;Kim et al, 2005;Whorwell et al, 2006;Guyonnet et al, 2007;Drouault-Holowacz et al, 2008;Enck et al, 2008;Sinn et al, 2008;Enck et al, 2009;Hong et al, 2009;Simrén et al, 2010;Guglielmetti et al, 2011;Sondergaard et al, 2011;Cha et al, 2012;Cui and Hu, 2012;Dapoigny et al, 2012;Ducrotte et al, 2012;Kruis et al, 2012;Begtrup et al, 2013;Roberts et al, 2013;Jafari et al, 2014;Lorenzo-Zuniga et al, 2014;Ludidi et al, 2014;Sisson et al, 2014;Yoon et al, 2014;Pineton de Chambrun et al, 2015;Yoon et al, 2015;Spiller et al, 2016;Mezzasalma et al, 2016;Thijssen et al, 2016;Hod et al, 2017;Sun et al, 2018) with 4,392 patients reported overall IBS symptoms improvement or response as a dichotomous outcome. There were two (Lorenzo-Zuniga et al, 2014;Mezzasalma et al, 2016) of these RCTs examining two different dose groups and one (Whorwell et al, 2006) examining three different dose groups.…”

“…In the subgroup of duration, 18 studies (Gade and Thorn, 1989;Nobaek et al, 2000;Niedzielin et al, 2001;Kim et al, 2005;Whorwell et al, 2006;Guyonnet et al, 2007;Drouault-Holowacz et al, 2008;Sinn et al, 2008;Guglielmetti et al, 2011;Cui and Hu, 2012;Dapoigny et al, 2012;Ducrotte et al, 2012;Jafari et al, 2014;Lorenzo-Zuniga et al, 2014;Ludidi et al, 2014;Yoon et al, 2014;Yoon et al, 2015;Sun et al, 2018) evaluated a shorter duration (< 8 weeks) and 17 studies (Kim et al, 2003;Kajander et al, 2005;Enck et al, 2008;Enck et al, 2009;Hong et al, 2009;Simrén et al, 2010;Sondergaard et al, 2011;Cha et al, 2012;Kruis et al, 2012;Begtrup et al, 2013;Roberts et al, 2013;Sisson et al, 2014;Pineton de Chambrun et al, 2015;Mezzasalma et al, 2016;Spiller et al, 2016;Thijssen et al, 2016;Hod et al, 2017) used a longer duration (≥ 8 weeks). The RR of group with less than 8 weeks was 1.55 (95% CI 1.27-1.89; Figure 4), and the RR of group with more than 8 weeks was 1.52 (95% CI 1.23-1.88), with significant heterogeneity (I 2 = 74%, P < 0.01; I 2 = 69%, P < 0.01, respectively).…”

Linaclotide increases cecal pH, accelerates colonic transit, and increases colonic motility in irritable bowel syndrome with constipation

“…Linaclotide is an orally active agonist of the guanylate cyclase C receptor (GC‐C), which is approved for the treatment of irritable bowel syndrome with constipation (IBS‐C) . Linaclotide binds with the GC‐C receptor on the luminal aspect of enterocytes and via a number of intracellular signaling cascades lead to increased intracellular cyclic guanosine monophosphate (cGMP).…”