Gastroesophageal reflux disease, irritable bowel syndrome and functional dyspepsia as overlapping conditions: focus on effect of trimebutine

Abstract

In their comprehensive review, de Bortoli et al [1] aimed to discuss the coexistence of gastroesophageal reflux disease (GERD) with irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the same patients and to evaluate the impact of diverse GERD treatments on the health-related quality of life (HR-QOL) of these patients; they mentioned 2 trials that reported resolution of the IBS symptoms in 20-40% of patients after proton pump inhibitor (PPI) therapy [1]. In one of these trials, we mainly observed [2] that trimebutine maleate is effective in the aforementioned overlapping disorders.Relative data indicate that the prevalence of overlaps of FD and/or IBS in GERD, GERD and/or IBS in FD, and GERD and/or FD in IBS is 46.9%, 47.6% and 34.4%, respectively, with worsened HR-QOL [3]. Moreover, Helicobacter pylori (H. pylori) infection could also be involved in GERD pathophysiology, at least in some national studies, as well as in FD and IBS patients [4,5].In this regard, our own preliminary data [2], also mentioned by the authors [1], showed that H. pylori is common in patients with GERD-IBS-FD and/or erosive esophagitis, while H. pylori eradication plus PPI and/or trimebutine regimens offer improvement in HR-QOL, mainly in patients who receive trimebutine. In a subsequent study, we confirmed our preliminary data [6], signifying the effectiveness of trimebutine in these overlapping populations.In overlapping disorders trimebutine could act: as a modulator of gastrointestinal tract motility being a promising candidate for treatment of hypermotility and hypomotility disorders [7]; by hastening gastric emptying, shortening the lag period, causing a premature phase III of the migrating motor complexes in the gut and controlling colonic contractile action [2,8]; by inducing release of gastrointestinal agents such as motilin; by modulating visceral sensitivity; by ameliorating symptoms such as diarrhea and abdominal pain [2,8]; and as a possible antimicrobial agent against bacteria that could trigger post-infectious functional gastrointestinal disorders [9,10], thereby requiring additional relative investigation. References

Trimebutine Maleate Monotherapy for Functional Dyspepsia: A Multicenter, Randomized, Double-Blind Placebo Controlled Prospective Trial

“…Such patients are characterized by a worse health-related quality of life (HR-QOL) score. Moreover, Hp- I has been as regarded as contributor in the pathogenesis, at least partly, of these overlapping entities [ 14 , 16 ]. Our preliminary data have demonstrated [ 13 ] that Hp -I is frequent in patients with GERD-IBS-FD and/or erosive esophagitis, and that Hp eradication, along with PPIs and/or TM regimens, offer improvement of HR-QOL, predominantly in patients treated with TM [ 13 ].…”

“…Mechanistically, Hp -induced mast cells are regarded as important effectors of the gut–brain axis that translate stress signals into the induction of variable neurotransmitters and proinflammatory mediators that might contribute to GI tract pathophysiology. Hp -stimulated chronic perceived stress results in decreased host defense and initiates intestinal inflammation through mast cell-dependent mechanisms, thereby signifying the activation of peripheral corticotropin-releasing factor receptors (CRF-Rs) and mast cells as significant mechanisms involved in stress-linked GI pathophysiology [ 14 , 16 ]. In this regard, recent data indicate that mast cell activation seems to play a role in FD pathophysiology [ 30 ].…”

“…It might also have possible antimicrobial properties against gastrointestinal bacteria that trigger postinfectious functional gastrointestinal disorders [ 14 , 15 ]. Importantly, almost all studies were conducted on TM and/or its combined regimens in irritable bowel syndrome (IBS) and/or FD overlapping disorders, but did not to evaluate TM monotherapy efficacy vs. placebo [ 14 , 16 ], TM vs. acotiamide, TM vs. mosapride or TM vs. domperidone [ 17 ]. TM, due to its mild side effects [ 18 , 19 ], can be substituted for other prokinetic agents that potentially exhibit severe opposing effects.…”

Does Irritable Bowel Syndrome Exist? Identifiable and Treatable Causes of Associated Symptoms Suggest It May Not

“…A better understanding of the pathophysiological origin of functional gastrointestinal symptoms related to IBS, GERD and FD may help improve treatment options [220]. In support of this hypothesis, there is empirical evidence to suggest that identification and treatment of a shared pathophysiological origin, H. pylori infection, may resolve overlapping symptoms of IBS, GERD, FD and/or erosive esophagitis in some cases [221]. It seems reasonable to suggest that personalized treatment of underlying pathophysiological causes of functional gastrointestinal symptoms could improve outcomes across a wide range of symptom-based diagnosis, not only IBS.…”

¿Existe relación entre <i>Helicobacter pylori</i> y el síndrome de intestino irritable?

“…Por ejemplo, Kountouras et al reportaron que en pacientes con DF y SII que recibieron tratamiento para H. pylori, presentaron una mejor respuesta a la trimebutina y al inhibidor de bomba de protones, en especial si se lograba la erradicación. Es posible que el efecto antiinflamatorio producto de la erradicación de H. pylori explique en parte la mejoría de los síntomas del SII, aunque esto debe ser verificado en estudios posteriores 61 .…”