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Ingestion of poorly digested, fermentable carbohydrates (fermentable oligo-, di-, mono-saccharides and polyols; FODMAPs) have been implicated in exacerbating intestinal symptoms and the reduction of intake with symptom alleviation. Restricting FODMAP intake is believed to relieve colonic distension by reducing colonic fermentation but this has not been previously directly assessed. We performed a randomised controlled trial comparing the effect of a low FODMAP diet combined with either maltodextrin or oligofructose on colonic contents, metabolites and microbiota. A parallel randomised controlled trial in healthy adults (n = 37). All subjects followed a low FODMAP diet for a week and supplemented their diet with either maltodextrin (MD) or oligofructose (OF) 7g twice daily. Fasted assessments performed pre- and post-diet included MRI to assess colonic volume, breath testing for hydrogen and methane, and stool collection for microbiota analysis. The low FODMAP diet was associated with a reduction in Bifidobacterium and breath hydrogen, which was reversed by oligofructose supplementation. The difference in breath hydrogen between groups post-intervention was 27ppm (95% CI 7 to 50, P<0.01). Colonic volume increased significantly from baseline in both groups (OF increased 110ml (19.6%), 95% CI 30ml to 190ml, P = 0.01; MD increased 90ml (15.5%), 95% CI 6ml to 175ml, P = 0.04) with no significant difference between them. Colonic volumes correlated with total breath hydrogen + methane. A divergence in Clostridiales abundance was observed with increased abundance of Ruminococcaceae in the maltodextrin group, while in the oligofructose group, Lachnospiraceae decreased. Subjects in either group with high methane production also tended to have high microbial diversity, high colonic volume and greater abundance of methanogens. A low FODMAP diet reduces total bacterial count and gas production with little effect on colonic volume.

Recent magnetic resonance imaging (MRI) studies showed that colonic volumes in children are different between health and functional constipation. The length of the colon has however been rarely measured and principally using unphysiological colon preparations or cadaver studies. The main objective of this study was to measure the length of the undisturbed colon in children with functional constipation (FC) and healthy controls. Here, the colon of 19 healthy controls (10–18 years old) and 16 children with FC (7–18 years old) was imaged using MRI. Different regions of the colon (ascending, transverse, descending, and sigmoid-rectum) were first segmented manually on the MRI images. Three-dimensional skeletonization image analysis methods were then used to reduce the regions of interest to a central, measurable line. Total colon length (corrected for body surface area) in healthy controls was 56±2 cm/m 2 (mean±SEM). Total colon length was significantly longer in children with FC 69±3 cm/m 2 compared to controls (p = 0.0037). The colon regions showing the largest differences between groups were the ascending colon (p = 0.0479) and the sigmoid-rectum (p = 0.0003). In a linear regression model, there was a positive significant correlation between total colon length and age (R = 0.45, p = 0.0064), height (R = 0.49, p = 0.0031), weight (R = 0.46, p = 0.0059) and colon volume (R = 0.4543, p = 0.0061). Our findings showed significant differences in colon lengths between healthy controls and children with constipation. A new objective diagnostic imaging endpoint such as colon length may help to improve knowledge of colon morphology and function and, in turn, understanding of colon functional pathology.

The gastrointestinal environment in which drug products need to disintegrate before the drug can dissolve and be absorbed has not been studied in detail due to limitations, especially invasiveness of existing techniques. Minimal in vivo data is available on undisturbed gastrointestinal motility to improve relevance of predictive dissolution models and in silico tools such as physiologically-based pharmacokinetic models. Recent advances in magnetic resonance imaging methods could provide novel data and insights that can be used as a reference to validate and, if necessary, optimize these models. The conventional method for measuring gastrointestinal motility is via a manometric technique involving intubation. Nevertheless, it is feasible to measure gastrointestinal motility with magnetic resonance imaging. The aim of this study was is to develop and validate a magnetic resonance imaging method using the most recent semi-automated analysis method against concomitant perfused manometry method. Eighteen healthy fasted participants were recruited for this study. The participants were intubated with a water-perfused manometry catheter. Subsequently, stomach motility was assessed by cine-MRI acquired at intervals, of 3.5min sets, at coronal oblique planes through the abdomen and by simultaneous water perfused manometry, before and after administration of a standard bioavailability / bioequivalence 8 ounces (~240mL) drink of water. The magnetic resonance imaging motility images were analysed using Spatio-Temporal Motility analysis STMM techniques. The area under the curve of the gastric motility contractions was calculated for each set and compared between techniques. The study visit was then repeated one week later. Data from 15 participants was analysed. There was a good correlation between the MRI antral motility plots area under the curve and corresponding perfused manometry motility area under the curve (r = 0.860) during both antral contractions and quiescence. Non-invasive dynamic magnetic resonance imaging of gastric antral motility coupled with recently developed, semi-automated magnetic resonance imaging data processing techniques correlated well with simultaneous, 'gold standard' water perfused manometry. This will be particularly helpful for research purposes related to oral absorption where the absorption of a drug is highly depending on the underlying gastrointestinal processes such as gastric emptying, gastrointestinal motility and availability of residual fluid volumes. This trial was registered at ClinicalTrials.gov as NCT03191045.

Complications of diverticular disease are increasingly common, possibly linked to increasing obesity. Visceral fat could contribute to the development of symptomatic diverticular disease through its pro-inflammatory effects. The study had 2 aims. A) to develop a semi-automated algorithm to measure abdominal adipose tissue from 2-echo magnetic resonance imaging (MRI) data; B) to use this to determine if visceral fat was associated with bowel symptoms and inflammatory markers in patients with symptomatic and asymptomatic diverticular disease. An observational study measuring visceral fat using MRI together with serum adiponectin, leptin, stool calprotectin and patient-reported somatisation and bowel habit. Medical and imaging research centres of a university hospital. MRI scans were performed on 55 patients after an overnight fast measuring abdominal subcutaneous and visceral adipose tissue volumes together with small bowel water content (SBWC). Blood and stool samples were collected and patients kept a 2 week stool diary and completed a somatisation questionnaire. Difference in the volume of visceral fat between symptomatic and asymptomatic patients. There were no significant differences in visceral (p = 0.98) or subcutaneous adipose (p = 0.60) tissue between symptomatic and asymptomatic patients. However measured fat volumes were associated with serum adipokines. Adiponectin showed an inverse correlation with visceral adipose tissue (VAT) (Spearman ρ = -0.5, p = 0.0003), which correlated negatively with SBWC (ρ = -0.3, p = 0.05). Leptin correlated positively with subcutaneous adipose tissue (ρ = 0.8, p < 0.0001). Overweight patients (BMI > 25 kgm-2) showed a moderate correlation between calprotectin and VAT (ρ = 0.3, p = 0.05). Somatization scores were significantly higher in symptomatic patients (p < 0.0003). Increasing visceral fat is associated with lower serum adiponectin and increased faecal calprotectin suggesting a pro-inflammatory effect which may predispose to the development of complications of diverticulosis.

The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosity, volume, and peristaltic wave speed). During local contractile activity, antegrade flows of 0.06–0.78 cm s−1 and backflows of −2.16–−0.21 cm s−1 were measured. Mean wall shear rates were strongly time and viscosity dependent although peaks were measured between 3.05–10.12 s−1 and 5.11–20.34 s−1 in the Dynamic Colon Model and its digital twin respectively, comparable to previous estimates of the USPII with paddle speeds of 25 and 50 rpm. It is recommended that viscosity and shear rates are considered when designing future dissolution test methodologies for colon-targeted formulations. In the USPII, paddle speeds >50 rpm may not recreate physiologically relevant shear rates. These findings demonstrate how the combination of biorelevant in vitro and in silico models can provide new insights for dissolution testing beyond established pharmacopeial methods.

Oral specially coated formulations have the potential to improve treatment outcomes of a range of diseases in distal intestinal tract whilst limiting systemic drug absorption and adverse effects. Their development is challenging, partly because of limited knowledge of the physiological and pathological distal gastrointestinal factors, including colonic chyme fluid distribution and motor function. Recently, non-invasive techniques such as magnetic resonance imaging (MRI) have started to provide novel important insights. In this feasibility study, we formulated a coated capsule consisting of a hydroxypropyl methylcellulose (HPMC) shell, coated with a synthetic polymer based on polymethacrylate-based copolymer (Eudragit®) that can withstand the upper gastrointestinal tract conditions. The capsule was filled with olive oil as MRI-visible marker fluid. This allowed us to test the ability of MRI to track such a coated capsule in the gastrointestinal tract and to assess whether it is possible to image its loss of integrity by exploiting the ability of MRI to image fat and water separately and in combination. Ten healthy participants were administered capsules with varying amounts of coating and underwent MRI imaging of the gastrointestinal tract at 45 min intervals. The results indicate that it is feasible to track the capsules present in the gastrointestinal tract at different locations, as they were detected in all 10 participants. By the 360 min endpoint of the study, in nine participants the capsules were imaged in the small bowel, in eight participants in the terminal ileum, and in four in the colon. Loss of capsule integrity was observed in eight participants, occurring predominantly in distal intestinal regions. The data indicate that the described approach could be applied to assess performance of oral formulations in undisturbed distal gastrointestinal regions, without the need for ionizing radiation or contrast agents.

Purpose: Knowledge of the length of the colon is relevant to understanding physiological and pathological function. It also has implications for diagnostic and clinical interventions, as well as for the design of delayed-release drug formulations and drug disposition modeling. Methods: Over the years, a range of different experimental methods have been employed to assess colon length. These methods vary from direct measurements on cadavers and during intraoperative procedures to measurements obtained from endoscopic and medical imaging techniques. However, no systematic review or meta-analysis of these findings has yet been carried out. In this systematic review, we identified 31 published experimental studies that measured the length of the human colon and/or its segments. Results: We synthesized the available data, comprising colon length measurements from 5741 adults and 337 children and young people, in a meta-analysis. The data contribute to our understanding of colon morphology and may have implications for clinical practice, particularly for colonoscopy and preoperative planning of surgical resections. Additionally, this review provides potential insights into anatomical correlates of functional diseases, such as constipation. Conclusions: This review highlights that non-invasive, non-destructive diagnostic imaging techniques, such as magnetic resonance imaging (MRI), can provide more physiologically relevant measurements of colon length. However, there is a need for more standardized measurement protocols and for additional pediatric data.

This work used in vivo MRI images of human colon wall motion to inform a biorelevant Dynamic Colon Model (DCM) to understand the interplay of wall motion, volume, viscosity, fluid, and particle motion within the colon lumen. Hydrodynamics and particle motion within the DCM were characterized using Positron Emission Tomography (PET) and Positron Emission Particle Tracking (PEPT), respectively. In vitro PET images showed that fluid of higher viscosity follows the wall motion with poor mixing, whereas good mixing was observed for a low viscosity fluid. PEPT data showed particle displacements comparable to the in vivo data. Increasing fluid viscosity favors the net forward propulsion of the tracked particles. The use of a floating particle demonstrated shorter residence times and greater velocities on the liquid surface, suggesting a surface wave that was moving faster than the bulk liquid. The DCM can provide an understanding of flow motion and behavior of particles with different buoyancy, which in turn may improve the design of drug formulations, whereby fragments of the dosage form and/or drug particles are suspended in the proximal colon.

Knowledge of luminal flow inside the human colon remains elusive, despite its importance for the design of new colon-targeted drug delivery systems and physiologically relevant in silico models of dissolution mechanics within the colon. This study uses magnetic resonance imaging (MRI) techniques to visualise, measure and differentiate between different motility patterns within an anatomically representative in vitro dissolution model of the human ascending colon: the dynamic colon model (DCM). The segmented architecture and peristalsis-like contractile activity of the DCM generated flow profiles that were distinct from compendial dissolution apparatuses. MRI enabled different motility patterns to be classified by the degree of mixing-related motion using a new tagging method. Different media viscosities could also be differentiated, which is important for an understanding of colonic pathophysiology, the conditions that a colon-targeted dosage form may be subjected to and the effectiveness of treatments. The tagged MRI data showed that the DCM effectively mimicked wall motion, luminal flow patterns and the velocities of the contents of the human ascending colon. Accurate reproduction of in vivo hydrodynamics is an essential capability for a biorelevant mechanical model of the colon to make it suitable for in vitro data generation for in vitro in vivo evaluation (IVIVE) or in vitro in vivo correlation (IVIVC). This work illustrates how the DCM provides new insight into how motion of the colonic walls may control luminal hydrodynamics, driving erosion of a dosage form and subsequent drug release, compared to traditional pharmacopeial methods.

Irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC) have significant personal, health care, and social impacts, affecting patients' quality of life. Treatment of these conditions is challenging. While green kiwifruit is a promising natural alternative to laxatives, its effectiveness in managing abdominal pain and the underlying mechanism of action is yet to be substantiated. This study investigates the effect of consuming 2 green kiwifruit daily for 4 weeks (the habitual serving) on abdominal pain and discomfort in individuals with IBS-C and FC. This study is a 2-arm parallel, open-label, placebo-controlled randomized study. This study's duration was 9 weeks, with a 3-week lead-in phase, a 4-week intervention phase, and a 2-week follow-up phase. A total of 60 participants with IBS-C and FC were randomized to consume either 2 Zespri green kiwifruit (Actinidia deliciosa \"Hayward,\" ~150 g per serving, ~90 kcal) or maltodextrin (calorie-matched to the fruit, ~25 g per serving, ~90 kcal) per day for 4 weeks. The participants completed validated questionnaires assessing digestive and general health and well-being parameters, underwent magnetic resonance imaging to determine colon physiological measures, ingested a blue food dye, provided blood and fecal samples to measure microbial, immunological, and biochemical parameters, and ingested wireless motility devices (selected participants only) to assess physiological processes. Recruitment for this study began in May 2021 and was completed in May 2022. A total of 63 participants were randomized, and 57 were analyzed using intention-to-treat analysis. Data analysis is complete, and full results are expected to be published in a peer-reviewed journal by April 2026. This study aims to evaluate the effectiveness of green kiwifruit consumption in managing abdominal pain in individuals with IBS-C and FC. It will provide new insights into the mechanisms behind the habitual consumption of green kiwifruit for digestive comfort in this population.