Table 1.
Summary findings on the link between gut peptides, functional dyspepsia, and gastroparesis.
| References | Peptide | Method | Subjects | Major findings |
|---|---|---|---|---|
| Jonnson et al. (30) | Gastrin | Gastrin dosage | FD patients | No altered gastrin levels. |
| He et al. (31) | Gastrin | Gastrin dosage | FD patients with delayed gastric emptying and HV | Higher gastrin levels |
| Walecka-Kapica et al. (32) | Gastrin | Gastrin dosage | PDS and EPS patients and HV | Higher gastrin levels |
| Yoshikawa et al. (33) | Gastrin | Gastrin dosage | FD patients on H2-blockers | Gastrin levels do not predict H2-blockers response |
| He et al. (29) | Somatostatin | Plasma somatostatin dosage and mucosal expression | FD with normal/delayed gastric emptying and HV | No differences between FD and HV |
| Jonnson et al. (30) | Somatostatin | Plasma somatostatin dosage | FD with normal/delayed gastric emptying and HV | Higher somatostatin levels associated with higher symptoms' burden and higher heartburn severity scores; rapid, transient, somatostatin peak during a stress interview |
| Russo et al. (34) | Somatostatin | Plasma somatostatin dosage | 42 PDS and 12 EPS patients | Somatostatin levels tendency to be lower in PDS vs. EPS, without reaching statistical significance |
| Katagiri et al. (35) | Somatostatin | Plasma somatostatin dosage | HV administered with Itopride | Acute increase of somatostatin levels |
| Foxx-Orenstein et al. (36) | Somatostatin | Somatostatin analog Octreotide administration | HV | Slowed gastric emptying, enhanced fasting gastric volumes and suppressed meal-induced volume increments |
| Yagi et al. (37) | Ghrelin | Ghrelin dosage | Gastroparesis and HV (multiple studies) | No significant difference between patients and HV |
| Kim et al. (38) | Ghrelin | Ghrelin dosage | PDS and EPS patients vs. HV | Significant correlation between ghrelin levels and symptom severity, namely epigastric pain in EPS, early satiation in PDS patients |
| Shindo et al. (39) | Ghrelin | Ghrelin dosage | PDS and EPS patients with NERD | Negative correlation between plasma ghrelin levels and gastric emptying rate in PDS but not with EPS patients |
| Takamori et al. (40) | Ghrelin | Ghrelin dosage | Dismotility-like dyspepsia patients (Rome II criteria) vs. HV | Lower Ghrelin levels vs. HV |
| Nishizawa et al. (41) | Ghrelin | Ghrelin dosage | FD patients vs. HV | Higher Ghrelin levels vs. HV |
| Pilichiewicz et al. (42) | Ghrelin | Ghrelin dosage | FD patients vs. HV with high-fat meal ingestion | Ingestion of the meal did not affect plasma ghrelin levels in FD vs. HV |
| Akamizu et al. (43) | Ghrelin | Ghrelin i.v. administration b.i.d. for 2 weeks | FD patients with loss of appetite | Significantly increased appetite and tendency to increased daily food intake in FD patients with loss of appetite |
| Arai et al. (44) | Ghrelin | Rikkunshito administration | FD patients | Improved upper gastrointestinal symptoms, correlating with increased plasm ghrelin levels |
| Suzuki et al. (45) | Ghrelin | Rikkunshito administration | Helicobacter pylori-infected participants with increased plasma ghrelin levels | Improved upper gastrointestinal symptoms |
| Gaddipati et al. (46) | Ghrelin | Ghrelin dosage | Idiopathic, diabetic and post-surgical Gastroparesis patients vs. HV gastroparesis | Increased ghrelin levels after sham feeding in HV and IG patients vs. diabetic and postsurgical gastroparesis |
| Tack et al. (47) | Ghrelin | Gastric emptying and meal-related symptoms evaluation | IG patients | Increased gastric emptying and improved symptoms |
| Murray et al. (48) | Ghrelin | Gastric emptying and meal-related symptoms evaluation | Diabetic gastroparesis patients | Increased gastric emptying |
| Binn et al. (49) | Ghrelin | Gastric emptying evaluation | Neurogenic Gastroparesis patients | Increased gastric emptying |
| Ejskjaer et al. (50) | Ghrelin | Ulimorelin (ghrelin agonist) i.v. administration | Diabetic gastroparesis patients | Increased gastric emptying |
| Heyland et al. (51) | Ghrelin | Ulimorelin (ghrelin agonist) i.v. administration vs. Metoclopramide | Critical ill patients with enteral feeding intolerance | Increased gastric emptying for both treatments, impossible differentiation |
| Ejskjaer et al. (52) | Ghrelin | TZP-102 (ghrelin agonist) Phase 2a study, 12 weeks study | Diabetic gastroparesis patients | Increased gastric emptying |
| Mc Callum et al. (53) | Ghrelin | TZP-102 ghrelin agonist) Phase 2b study, 12 weeks study | Diabetic gastroparesis patients | Failed to confirm Increased gastric emptying |
| Lembo et al. (54) | Ghrelin | Relamorelin injections | Diabetic gastroparesis patients | Reduced vomiting frequency/severity; accelerated gastric emptying |
| Camilleri et al. (55) | Ghrelin | Relamorelin injections | Diabetic gastroparesis patients | Accelerated gastric emptying |
| Russo et al. (34) | Motilin | Motilin dosage | PDS and EPS patients | Higher motilin levels in EPS vs. PDS patients |
| Labo et al. (56) | Motilin | Motilin dosage | FD patients with delayed gastric emptying | Absence of motilin levels fluctuations during the interdigestive state; gastric phase III contractions absence |
| Achem-Karam et al. (57) | Motilin | Motilin dosage | Diabetic gaastroparesis patients | Elevated and fluctuating motilin plasma levels during the interdigestive state; antral phase III activity is absent |
| Talley et al. (58) | Motilin | ABT-229 administration | FD patients with and without delayed gastric emptying | No significant symptoms improvement |
| Talley et al. (59) | Motilin | ABT-229 administration | Type 1 diabetes mellitus patients | No significant symptoms improvement |
| McCallum et al. (60) | Motilin | Mitemcinal | Patients with idiopathic and diabetic gastroparesis | Accelerates gastric empying |
| Mccallum et al. (61) | Motilin | Mitemcinal | Diabetic patients with gastroparesis symptoms | Symptoms relief vs. placebo |
| Cuomo et al. (62) | Motilin | Motilin dosage | HV | Contraction of proximal stomach, increases satiety |
| Deloose et al. (63) | Motilin | Camicinal | HV | Stimulates MMC and gastric emptying |
| Hellstrom et al. (64) | Motilin | Camicinal single dose administration (25, 50, or 125 mg) | Type 1 Diabetic patients with gastroparesis symptoms | significantly accelerated gastric emptying of solids by 125 mg dose |
| Barton et al. (65) | Motilin | Camicinal | Diabetic patients with gastroparesis symptoms | Significantly accelerated gastric emptying |
| Chapman et al. (66) | Motilin | Camicinal | Critical ill patients with enteral feeding intolerance | Camicinal single dose (50 mg) acceleratedgastric emptying and increased glucose absorption |
| Chiloiro et al. (67) | CCK | Standard solid-liquid meal (gastric emptying) | H. pylori associated dyspepsia patients | Significantly lower basal values compared to H. pylori negative patients |
| Bharucha et al. (27) | CCK | Intraduodenal dextrose and lipid adminstration | FD patients vs. HV | Correlation between plasma concentrations of CCK and provoked symptoms Early increase of CCK plasma levels |
| Barbera et al. (68) | CCK | Intraduodenal administration of lipids | FD patients | Increases sensitivity to gastric distention |
| Feinle et al. (69) | CCK | Duodenal lipid infusion + CCK-A antagonist dexloxiglumide | FD patients | Lipid increased plasma CCK levels Dexloxiglumide reduced gastric compliance Gastric distention relieved by dexloxiglumide |
| van Boxel et al. (70) | CCK | Duodenal perfusion | FD patients vs. HV | Mean mucosal CCK concentration was lower in FD patients |
| Feinle-Bisset et al. (71) | CCK | High (HF) and low (LF) fat yogurt | FD patients | Plasma CCK was higher after HF compared to LF |
| Rotondo et al. (72) | GLP-1 | Dipeptidyl peptidase-4 inhibitor (vildagliptin) | HV | Inhibition of gastric accommodation and increased GLP-1 plasma levels |
| Mano et al. (73) | GLP-1 | Hot water and broth (with rice) | HV | Rise in GLP-1 after ingestion of synthesized broth |
| Witte et al. (74) | GLP-1 | Liquid meal | FD patients (EPS) | Similar GLP-1 levels to HV, correlation with nausea |
| Pilichiewicz et al. (42) | PYY | PYY dosage | FD patients vs. HV with high-fat meal ingestion | Lower postprandial PYY levels compared to HV |
| Witte et al. (74) | PYY | Liquid meal | FD patients (EPS) | PYY3-36 is correlated with the sensation of fullness |
| Tack et al. (75) | 5-HT | Cisapride (5-HT4 agonist) | HV | Enhances gastric distension and accommodation |
| Kessing et al. (76) | 5-HT | Prucalopride (5-HT4 agonist) | HV after a standardized meal | Accelerates gastric emptying in male volunteers |
| Carbone et al. (77) | 5-HT | Prucalopride (5-HT4 agonist) | Patients with gastroparesis | Enhances gastric emptying |
| Netzer et al. (78) | 5-HT | Ondansetron (5-HT3 antagonist) | HV | No effect on gastric emptying |
| Janssen et al. (79) | 5-HT | Ondansetron (5-HT3 antagonist) | HV | No effect on gastric compliance, gastric tone |
| Van Oudenhove et al. (80) | 5-HT | Busprione (5-HT1A agonist) | HV | Relaxation of the proximal stomach + decreases gastric emptying |
| Tack et al. (81) | 5-HT | Busprione (5-HT1A agonist) | FD patients | Decreased symptoms + increased gastric accommodation |
| Geeraerts et al. (82) | 5-HT | Acute tryptophan depletion | HV | Reduction in 5-HT levels in duodenum |
| Tack et al. (83) | 5-HT | Paroxetine | HV | Enhances gastric accommodation |
| Janssen et al. (84) | 5-HT | Citalopram (5-HT reuptake inhibitor) | HV | Preprandial gastric relaxation, lower postprandial volume increase + enhances liquid emptying |
| Jannsen et al. (85) | 5-HT | Citalopram (5-HT reuptake inhibitor) | HV | Suppresses gastric phase 2 Stimulates intestinal phase 3 |
| Wilmer et al. (86) | 5-HT | Ondansetron (5-HT3 antagonist) | HV | Suppresses gastric component of phase 3 |
| Chueng et al. (87) | 5-HT | 5-HT postprandial levels | FD patients | Decreased levels of 5-HT |