Semi-solid and solid bolus swallows in high-resolution oesophageal manometry for the detection of motility disorders

Background/Aims: High-resolution oesophageal manometry utilises water swallows to evaluate oesophageal function. However, small volumes of water are not representative of normal eating and as a result often produce normal manometry studies in patients with dysphagia. This study sets out to establish optimal diagnostic thresholds for semi-solid solid swallows and evaluate their ability to uncover motility abnormalities in patients with motility disorders. Method: Manometry was performed using ten 5-mL single water swallows followed by two semi-solid and two solid swallows in the upright position. Normative values for the adjunctive tests were obtained from patient controls while patients with major motility disorders were used to establish the optimal diagnostic thresholds. Diagnostic thresholds identified were prospectively tested in patients with normal water swallows but oesophagus related symptoms and in those with minor and major motility disorders. Results: Normal values for semi-solid and solid were determined in patient controls (n = 100). Development of diagnostic thresholds included 120 patients with major motility disorders. Optimal diagnostic thresholds identified for oesophagogastric junction dysfunction in semi-solid and solid swallows (IRP > 15.5 mmHg). Hypercontractilty and spasm used existing thresholds (>8000 mmHg-s-cm and < 4.5 s, respectively) but modified frequency of ≥50% of adjunctive swallows. Diagnostic thresholds were applied to symptomatic patients with normal water swallows (n = 70) identifying 12/70 (17%) to have abnormal adjunctive swallows. One of 30 patients (3%) with ineffective motility had abnormal adjunctive swallow and 12 patients with oesophageal spasm, oesophagogastric junction obstruction, and hypercontractility had abnormal adjunctive swallows that moved them up the motility disorder hierarchy. Conclusions: Semi-solid and solid challenge increase diagnostic yield of motility disorders

New Internet of Medical Things for home-based treatment of anorectal disorders

Home-based healthcare provides a viable and cost-effective method of delivery for resource and labour-intensive therapies, such as rehabilitation therapies, including anorectal biofeedback. However, existing systems for home anorectal biofeedback are not able to monitor patient compliance or assess the quality of exercises performed, and as a result have yet to see wide spread clinical adoption. In this paper, we propose a new Internet of Medical Things (IoMT) system to provide home-based biofeedback therapy, facilitating remote monitoring by the physician. We discuss our user-centric design process and the proposed architecture, including a new sensing probe, mobile app, and cloud-based web application. A case study involving biofeedback training exercises was performed. Data from the IoMT was compared against the clinical standard, high-definition anorectal manometry. We demonstrated the feasibility of our proposed IoMT in providing anorectal pressure profiles equivalent to clinical manometry and its application for home-based anorectal biofeedback therapy

Rheological characteristics of soluble fibres during chemically simulated digestion and their suitability for gastroparesis patients

Dietary fibres are an integral part of a balanced diet. Consumption of a high-fibre diet confers many physiological and metabolic benefits. However, fibre is generally avoided by individuals with gastrointestinal motility disorders like gastroparesis due to increased likelihood of exacerbated symptoms. Low-viscosity soluble fibres have been identified as a possible source of fibre tolerable for these individuals. The aim of this study is to determine the rheological properties of 10 common commercially available soluble fibres in chemically simulated digestive conditions and evaluate their suitability for individuals with mild to moderate gastroparesis, a gastric motility disorder. Rheological testing under neutral condition (distilled water pH 7) and chemically simulated gastric digestion were evaluated to determine the yield point and relative viscosity of each fibre. Our results reveal two rheological categories of soluble fibres; pseudoplastic and dilatant.Simulated digestion was shown to significantly alter the yield-points of psyllium husk, iotacarrageenan, beta-glucan, apple-fibre pectin, and inulin. Gum Arabic and partially hydrolysed guar gum showed the lowest viscosities and were not affected under simulated digestion, characteristics that make them potential candidate fibres for patients with gastroparesis. Altogether, our results demonstrate that digestion can have a significant impact on fibre viscosity and should be taken into consideration when evaluating the suitability of fibres for patients with gastric motility disorders

Prevalence and effects of gastro-oesophageal reflux during spirometry in subjects undergoing reflux assessment

Variability during spirometry can persist despite control of technical and personal factors. We postulate spirometry induces gastro-oesophageal reflux (GOR), which may cause variability and affect results of spirometry. Fifty-eight (58) subjects undergoing GOR investigation with oesophageal manometry and 24hr pH monitoring were recruited. Oesophageal dysmotility and GOR were assessed as part of clinical care. Subjects performed 2 sets of spirometry separated by a 10-minute rest period. The assessment of GOR during spirometry procedure (defined by a lower oesophageal pH<4) started from the first set of spirometry and concluded when the second set of spirometry was completed. We calculated variability (%) of FEV1, FVC and PEFR within each set as well as changes over 10-minutes. Twenty-six subjects (45%) recorded GOR during assessment. Of these, 23 subjects recorded GOR during the 10-minute rest period. Four subjects had GOR recorded only during spirometry tests. We did not find variability of spirometry parameters between the groups with and without GOR during spirometry procedure. However, in subjects with GOR, we found small but significant reductions of PEFR (0.5L/s, 8%, p<0.001) and FEV1 (84 mL, 3%, p = 0.048) in the second set of spirometry compared to the first spirometry set. This pilot study demonstrates that GOR can occur during and following spirometry. Presence of GOR during spirometry in this patient population caused small decreases in PEFR and FEV1 when it is repeated 10-minutes later however not increase variability in a single series of measurements

A HPLC-ESI-Q-ToF-MS method for the analysis of monomer constituents in PHGG, gum arabic and psyllium husk prebiotic dietary fibre supplements

“Soluble” type dietary fibre contains polysaccharides with monomer constituents that play a major role in lowering the glycemic index of food (“low-GI”) and improving colonic health through gut microbiome fermentation. Soluble fibres such as partially hydrolysed guar gum (PHGG), gum Arabic and psyllium husk are of particular interest in gastrointestinal research, exploring their effects in motility disorders such as gastroparesis, constipation, diarrhea and irritable bowel syndrome (IBS) is important. The primary aim of this research was to develop a rapid pre-column derivatized HPLC-ESI-Q-ToF-MS method for the identification and quantification of monomer sugar constituents in commercial dietary fibre supplements of PHGG, gum Arabic and psyllium husk. Polysaccharides in the samples were hydrolysed and derivatized using 1-phenyl-3-methyl-5-pyrazolone (PMP). A rapid 21 min HPLC-ESI-Q-ToF-MS method separated nine different PMP-labelled monomer sugars. Five different sugars (i.e., Galactose, Arabinose, Rhamnose, Mannose and Xylose) were identified and quantified. Standard curve linearity was excellent (R2 > 0.999), with good intra-laboratory precision (< ±5% SD for concentrations, ≤ ±0.02 min peak shifting for retention times). The average three-level (50%, 75% and 100%) spiking recoveries for the analytes was acceptable (96.22–109.49%). Positive scanning mode ESI-MS/MS was used to generate [M + H]+ precursor ions and three (m/z) product ion fragments to provide identity confirmation. The concentrations of monomer sugars in gum Arabic and psyllium husk dietary fibres were consistent with literature reports. In PHGG, the concentration of galactose was unexpectedly higher than mannose, indicating that the commercial hydrolysis process of guar gum during PHGG manufacturing affected monomer composition. The method presented here provides the basis for the standardisation and labelling of commercial PHGG, gum Arabic and psyllium husk supplements. Future research will need to explore the monomer variability in other prebiotic soluble fibres and their efficacy in the production of beneficial short-chain fatty acids (SCFA) in the colonic environment

Understanding the biology of human interstitial cells of Cajal in gastrointestinal motility

Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility

Transcriptome and proteome profiling of primary human gastric interstitial cells of Cajal predicts pacemaker networks

Background/Aims Interstitial cells of Cajal (ICC) are specialized gastrointestinal (GI) pacemaker cells required for normal GI motility. Dysfunctions in ICC have been reported in patients with GI motility disorders, such as gastroparesis, who exhibit debilitating symptoms and greatly reduced quality of life. While the proteins, calcium-activated chloride channel anoctamin-1 (ANO1) and the receptor tyrosine kinase (KIT), are known to be expressed by human ICC, relatively little is known about the broad molecular circuitry underpinning human ICC functions. The present study therefore investigates the transcriptome and proteome of ANO1-expressing, KITlow/CD45–/CD11B– ICC obtained from primary human gastric tissue. Methods Excess human gastric tissue resections were obtained from sleeve gastrectomy patients. ICC were purified using fluorescence-activated cell sorting (FACSorting). Then, ICC were characterized by using immunofluorescence, real-time polymerase chain reaction, RNA-sequencing and mass spectrometry. Results Compared to unsorted cells, real-time polymerase chain reaction showed the KITlow/CD45–/CD11B– ICC had: a 9-fold (P 10-fold, P 4-fold, P < 0.05). RNA-sequencing and gene ontology analyses of the KITlow/ CD45–/CD11B– cells revealed a transcriptional profile consistent with ICC function. Similarly, mass spectrometry analyses of the KITlow/ CD45–/CD11B– cells presented a proteomic profile consistent with ICC activities. STRING-based protein interaction analyses using the RNA-sequencing and proteomic datasets predicted protein networks consistent with ICC-associated pacemaker activity and ion transport. Conclusion These new and complementary datasets provide a valuable molecular framework for further understanding how ICC pacemaker activity regulates smooth muscle contraction in both normal GI tissue and GI motility disorders

Distinct microbiota dysbiosis in patients with non-erosive reflux disease and esophageal adenocarcinoma

Non-erosive reflux disease (NERD) and esophageal adenocarcinoma (EAC) are often regarded as bookends in the gastroesophageal reflux disease spectrum. However, there is limited clinical evidence to support this disease paradigm while the underlying mechanisms of disease progression remain unclear. In this study, we used 16S rRNA sequencing and mass-spectrometer-based proteomics to characterize the esophageal microbiota and host mucosa proteome, respectively. A total of 70 participants from four patient groups (NERD, reflux esophagitis, Barrett’s esophagus, and EAC) and a control group were analyzed. Our results showed a unique NERD microbiota composition, distinct to control and other groups. We speculate that an increase in sulfate-reducing Proteobacteria and Bacteroidetes along with hydrogen producer Dorea are associated with a mechanistic role in visceral hypersensitivity. We also observed a distinct EAC microbiota consisting of a high abundance of lactic acid-producing bacteria (Staphylococcus, Lactobacillus, Bifidobacterium, and Streptococcus), which may contribute towards carcinogenesis through dysregulated lactate metabolism. This study suggests the close relationship between esophageal mucosal microbiota and the appearance of pathologies of this organ

Non-erosive reflux disease and oesophageal carcinoma : risk assessment is complicated by the dynamic nature of reflux disease

Gastroesophageal reflux disease is a pervasive health concern, affecting a substantial proportion of the global population. Prevalence ranges from 10% to 20% in North America and Europe, and around 5% in Asian countries. The conventional diagnostic approach involves endoscopic assessment of oesophageal mucosa, particularly in cases where patients report high risk symptoms (ie,dysphagia, bleeding, vomiting, and anaemia) or did not respond to proton pump inhibitor treatment. The established association between gastroesophageal reflux disease with erosive oesophagitis and mucosal abnormalities and anincreased risk of oesophageal adenocarcinoma is widely acknowledged. However, a substantial proportion (60-70%) of patients with gastroesophageal reflux disease have non-erosive reflux disease, with no signs of erosion on endoscopy. Their risk of oesophageal adenocarcinoma remains relatively unexplored

The short-term effects and tolerability of low-viscosity soluble fibre on gastroparesis patients : a pilot clinical intervention study

Gastroparesis is a motility disorder that causes severe gastric symptoms and delayed gastric emptying, where the majority of sufferers are females (80%), with 29% of sufferers also diagnosed with Type-1 or Type-2 diabetes. Current clinical recommendations involve stringent dietary restriction and includes the avoidance and minimization of dietary fibre. Dietary fibre lowers the glycaemic index of food, reduces inflammation and provides laxation. Lack of dietary fibre in the diet can affect long-term gastrointestinal health. Our previously published rheological study demonstrated that “low-viscosity” soluble fibres could be a potentially tolerable source of fibre for the gastroparetic population. A randomised controlled crossover pilot clinical study was designed to compare Partially-hydrolysed guar gum or PHGG (test fibre 1), gum Arabic (test fibre 2), psyllium husk (positive control) and water (negative control) in mild-to-moderate symptomatic gastroparesis patients (requiring no enteral tube feeding). The principal aim of the study was to determine the short-term physiological effects and tolerability of the test fibres. In n = 10 female participants, post-prandial blood glucose, gastroparesis symptoms, and breath test measurements were recorded. Normalized clinical data revealed that test fibres PHGG and gum Arabic were able to regulate blood glucose comparable to psyllium husk, while causing far fewer symptoms, equivalent to negative control. The test fibres did not greatly delay mouth-to-caecum transit, though more data is needed. The study data looks promising, and a longer-term study investigating these test fibres is being planned