Gastrointestinal Transit Time Research Articles

Clostridioides difficile infection promotes gastrointestinal dysfunction in human and mice post-acute phase of the disease

ObjectivesIn the US, Clostridioides difficile (C. difficile) infection (CDI) is the 8th leading cause for hospital readmission and 7th for mortality among all gastrointestinal (GI) disorders. Here, we investigated GI dysfunction post-CDI in human and mice post-acute infection. Materials and methodsFrom March 2020 to July 2021, we reviewed the clinical records of 67 patients referred to the UVA Complicated C. difficile clinic for fecal microbiota transplantation (FMT) eligibility. In vivo, C57BL/6 mice were infected with C. difficile and clinical scores were determined daily. Stool samples from mice were collected to measure the shedding of C. difficile and myeloperoxidase (MPO) levels. On day 21 post-infection, Evans's blue and FITC-70kDa method were performed to evaluate GI motility in mice. ResultsOf the 67 patients evaluated at the C. difficile clinic, 40 patients (59.7%) were confirmed to have CDI, and 22 patients (32.8%) with post-CDI IBS (diarrhea-type, constipation-type, and mixed-type). In infected mice, levels of MPO in stools and clinical score were higher on day 3. On day 21, mice have recovered from body weight loss induced by CDI, and fecal MPO was undetectable. The total GI transit time (TGITT) and FITC-70kDa levels on proximal colon were increased in infected mice (p = 0.002), suggesting a constipation phenotype post-acute phase of CDI. A positive correlation on intestinal inflammation on day 3 and TGITT on day 21 was observed. ConclusionIn conclusion, post-infection intestinal dysfunction occurs in humans and mice post-CDI. Importantly, we have validated in the mouse model that CDI causes abnormal GI transit in the recovery phase of the disease, indicating the potential utility of the model in exploring the underlying mechanisms of post-infectious IBS in humans.

A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study

Background and objective A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects. Methods Male and female subjects (n = 135; age: 25–60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured. Results CL18100F4 supplementation significantly (p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved (p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly (p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants’ vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges. Conclusion The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.

Pharmacokinetics and tolerability of single-dose enteral cannabidiol and cannabidiolic acid rich hemp in horses (Equus caballus).

The pharmacokinetics and tolerability of cannabinoids and their metabolites were determined in eight horses after enteral administration of a commercial CBD/CBDA-rich hemp oil product. Each horse was administered 2 mg/kg or 8 mg/kg CBD/CBDA or no treatment in a randomized cross-over design. Serial serum samples collected over 48 h were analyzed by high performance liquid chromatography with tandem mass spectrometry. Plasma chemistry analysis was performed at 0 h and 24 h. Vital parameters, pedometry, and blinded mentation and gait evaluations were recorded at intervals up to 24 h. Manure production and gastrointestinal transit time were tracked for 48 h after oil administration. The median maximal concentration of CBD and CBDA were 5.2 and 36.95 ng/mL in the 2 mg/kg group, respectively; and 40.35 and 353.56 ng/mL in the 8 mg/kg group. The median half-life of elimination was not calculated for the 2 mg/kg CBD treatment due to lack of time points above the lower quantifiable limit beyond the Cmax while it was 7.75 h in the 8 mg/kg group. CBDA absorption was biphasic. Pharmacokinetic parameters for tetrahydrocannabinol, tetrahydrocannabinolic acid, cannabigerolic acid, and 7-carboxy cannabidiol are also reported. No significant differences in any of the measured tolerability parameters were demonstrated between treatment groups. Single-dose enteral administration of CBD/CBDA-rich hemp extract up to 8 mg/kg does not appear to produce neurologic, behavioral, or gastrointestinal effects in horses.

Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial

Aims/hypothesisDiabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study.MethodsThis study included adults (aged 20–86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function.ResultsSixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: −0.26 ± 0.64 vs −0.17 ± 0.62, p=0.44; GSRS: −0.35 ± 0.62 vs −0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: −0.47 ± 0.78 vs −0.33 ± 0.75, p=0.34; GSRS: −0.46 ± 0.90 vs −0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs −19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated.Conclusions/interpretationCervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy.Trial registrationClinicalTrials.gov NCT04143269FundingThe study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045)Graphical

Glycation reactions of methylglyoxal during digestion in a dynamic, in vitro model of the upper gastrointestinal tract (TIM‐1)

AbstractThe 1,2‐dicarbonyl compound methylglyoxal (MGO) can react with and thereby impair the function of proteins and DNA, leading to pathophysiological pathways in vivo. However, studies on the bioavailability of dietary MGO and its reactions during digestion have diverging results. Therefore, simulated digestion experiments of MGO, protein, and creatine were performed in the dynamic, in vitro model of the upper gastrointestinal tract (TIM‐1). This multicompartment model continuously adjusts pH values and has realistic gastrointestinal transit times while also removing water and metabolites by dialysis. Samples were analyzed with HPLC‐UV for MGO and HPLC–MS/MS for creatine and glycated amino compounds. MGO reacted with creatine during simulated digestion in TIM‐1 to form the hydroimidazolone MG‐HCr in similar amounts as in a human intervention study. 28%–69% of MGO from the meal were passively absorbed in TIM‐1, depending on the addition of creatine and protein. Simultaneous digestion of MGO with ovalbumin led to the formation of the lysine adduct Nε‐carboxyethyllysine (CEL) and the methylglyoxal‐derived hydroimidazolone of arginine (MG‐H1). The formation of both compounds decreased with added creatine. Hence, glycation compounds are formed during digestion and significantly contribute to other ingested dietary glycation compounds, whose physiological consequences are critically discussed.

In Vivo Predictive Dissolution and Biopharmaceutic-Based In Silico Model to Explain Bioequivalence Results of Valsartan, a Biopharmaceutics Classification System Class IV Drug.

The purpose of this study was to predict the in vivo bioequivalence (BE) outcome of valsartan (VALS, BCS class IV) from three oral-fixed combination products with hydrochlorothiazide (HCTZ, BCS class III) (Co-Diovan® Forte as reference and two generic formulations in development) by conducting in vivo predictive dissolution with a gastrointestinal simulator (GIS) and a physiologically based biopharmaceutic model (PBBM). In the first BE study, the HCTZ failed, but the VALS 90% CI of Cmax and the AUC were within the acceptance limits, while, in the second BE study, the HCTZ 90% CI of Cmax and the AUC were within the acceptance limits, but the VALS failed. As both drugs belong to different BCS classes, their limiting factors for absorption are different. On the other hand, the gastrointestinal variables affected by the formulation excipients have a distinct impact on their in vivo exposures. Dissolution tests of the three products were performed in a GIS, and a PBBM was constructed for VALS by incorporating in the mathematical model of the in vitro-in vivo correlation (IVIVC) the gastrointestinal variables affected by the excipients, namely, VALS permeability and GI transit time. VALS permeability in presence of the formulation excipients was characterized using the in situ perfusion method in rats, and the impact of the excipients on the GI transit times was estimated from the HCTZ's in vivo results. The model was able to fit the in vivo BE results with a good prediction error. This study contributes to the field by showing the usefulness of PBBM in establishing in vitro-in vivo relationships incorporating not only dissolution data but also other gastrointestinal critical variables that affect drug exposure in BCS class IV compounds.

Gastroretentive Drug Delivery Systems with improved Floating and Swelling Capabilities

For medications with an absorption window in the stomach and upper part of small intestine, a controlled drug delivery system with a longer stomach residence duration can be particularly useful. Rapid gastrointestinal transit may cause drug delivery system above the absorption zone to only partially release drug, which would reduce the supplied dose's effectiveness. The main drawbacks are linked to the non-uniformity of drug absorption across the alimentary canal and the inter- and intra-subject variability of gastro-intestinal transit time. The bioavailability of medications is predicted to be improved by floating delivery systems, which are designed to stay buoyant on the gastric contents for an extended period of time. Floating in combination with swellable system gaining attention due to their wide applicability in the targeting of drugs to stomach. These floating and swellable tablet have the advantage that they remain buoyant and swells to 2-3 folds in gastric fluid.

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats.

Introduction Exposure to bisphenol A (BPA), a toxic chemical released from plastic, affects various body functions, including reproduction, metabolism, and development. The most common route of exposure to BPA is oral, and the gastrointestinal(GI) tract is, therefore, the first body system to be exposed to BPA. BPA has been well-documented to impair gut contractility in rats, in vitro. It may therefore be hypothesized that BPA may adversely affect GI motility and hence slow down the movement of food, resulting in the increased transit of food bolus in the GI tract. There are no reports so far on the effects of BPA on GI transit time. Objectives The present study was undertaken to examine the impact of exposure to BPA by a single oral dose (termed as short-term ingestion of BPA) and chronic (28-day) oral dose (termed as long-term ingestion of BPA) on the transit time of food bolus in the gut of adult male albino rats. Methods and materials The study was conducted in the Department of Physiology,Institute of MedicalSciences,Banaras Hindu University, Varanasi,Uttar Pradesh, India. In one set of experiments, each animal was fed a food pellet, once (short-term ingestion) containing BPA (2 µg/kg and 50 µg/kg in different groups), and in another set of experiments, each animal was fed a food pellet containing BPA (50 µg/kg/day) for 28 consecutive days (long-term ingestion). Control rats in both sets were fed food pellets without BPA. Subsequently, the gastric transit index (GTI), ileocecal transit index (ICTI), and colonic transit time (CTT) were determined by the standard charcoal marker method. Results One-time ingestion of a food pellet containing BPA caused a significant (p < 0.05) drop in the GTI and ICTI and an increase in the CTT with both doses of BPA (2 and 50 µg/kg). Similarly, after chronic (28-day), oral BPA exposure, a significant decrease in the GTI and ICTT and an increase in CTT were observed. Conclusion Both short-term (one-time) and long-term (28-day) oral exposure to BPA-containing food harmed GI transit. Slow GI transit may lead to metabolic disorders and GI motility disorders, such as constipation.

Early time-restricted eating improves markers of cardiometabolic health but has no impact on intestinal nutrient absorption in healthy adults

Early time-restricted eating (eTRE) improves aspects of cardiometabolic health. Although the circadian system appears to regulate nutrient absorption, little is known about the effects of eTRE on intestinal absorption. In this randomized crossover trial, 16 healthy adults follow a controlled, weight maintenance diet for 9days, consuming all calories between 0800 and 1400 (eTRE schedule) or 0800 and 2000 (control schedule). We measure the energy content of the diet, stool, and urine with bomb calorimetry and calculate intestinal energy absorption. The eTRE schedule is more effective than the control eating schedule for improving markers of cardiometabolic health, including 24-h mean glucose concentrations and glycemic variability, assessed as the mean amplitude of glycemic excursions. However, eTRE has no effect on intestinal energy and macronutrient absorption, gastrointestinal transit time, colonic hydrogen gas production, or stool microbial composition, suggesting eTRE does not impact gastrointestinal function. This trial is registered (ClinicalTrials.gov: NCT04877262).

Guava fibre characterization and effects on digestibility, fermentation products, gastrointestinal transit time and palatability of dry diets for dogs.

The use of fruit fibres as a way of reusing industrial waste is attractive and necessary, increasing the efficiency and reducing the environmental impact of the industry. This study characterized guava fibre as a fibrous ingredient and evaluated its effects when included in extruded diets for dogs on nutrient digestibility, faecal traits, fermentation products, gastrointestinal transit timeand palatability. Four diets were formulated: CO (control diet, no fibrous ingredients added), GF3 (3% guava fibre), GF6 (6% guava fibre)and GF12 (12% guava fibre). The guava fibre was added to diets in replacement of maize, with small adjustments in the other ingredients to ensure similar contents of protein and fat. The diets were fed to 24 adult Beagle dogs (6 per diet) during 15 days for adaptation followed by 15 days for assessment of digestibility, fermentation end productsand gastrointestinal transit time. The palatability of G6 and G12 treatments was evaluated against the CO by the two-pan test. Results were compared by analysis of variance and polynomial contrasts according to the guava fibre inclusion level (p < 0.05). The addition of guava fibre did not change nutrient intake except for the increase on dietary fibre (p < 0.001). Fibre inclusion resulted in a quadratic reduction in total tract apparent digestibility for dry matter, organic matter, crude protein and crude energy (p < 0.001), and on the metabolizable energy content of the foods (p < 0.001). Guava fibre addition did not change the faecal concentration of ammonia, lactic acid, faecal pHand branched chain fatty acids but it decreased acetic and propionic acids concentration (p < 0.01). The inclusion of 12% guava fibre did result in a faster transit time (p = 0.046) compared to the control diet. Guava fibre can be characterized as a novel insoluble non-fermentable fibre source that could be safely used in levels up to 12% in canine extruded diets.

Analysis of Gut Characteristics and Microbiota Changes with Maternal Supplementation in a Neural Tube Defect Mouse Model

Adequate nutrient supply is crucial for the proper development of the embryo. Although nutrient supply is determined by maternal diet, the gut microbiota also influences nutrient availability. While currently there is no cure for neural tube defects (NTDs), their prevention is largely amenable to maternal folic acid and inositol supplementation. The gut microbiota also contributes to the production of these nutrients, which are absorbed by the host, but its role in this context remains largely unexplored. In this study, we performed a functional and morphological analysis of the intestinal tract of loop-tail mice (Vangl2 mutants), a mouse model of folate/inositol-resistant NTDs. In addition, we investigated the changes in gut microbiota using 16S rRNA gene sequencing regarding (1) the host genotype; (2) the sample source for metagenomics analysis; (3) the pregnancy status in the gestational window of neural tube closure; (4) folic acid and (5) D-chiro-inositol supplementation. We observed that Vangl2+/Lp mice showed no apparent changes in gastrointestinal transit time or fecal output, yet exhibited increased intestinal length and cecal weight and gut dysbiosis. Moreover, our results showed that the mice supplemented with folic acid and D-chiro-inositol had significant changes in their microbiota composition, which are changes that could have implications for nutrient absorption.

A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation

Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B.longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B.longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.

Effect of type of fiber and its physicochemical properties on performance, digestive transit time, and cecal fermentation in broilers from 1 to 23 d of age

The effects of insoluble fiber (IF) sources differing on particle size and hydration capacity (HC) on growth performance, gastrointestinal tract (GIT) development, cecal fermentation, and digestive transit time were investigated from 1 to 23 d of age in 550 Ross-308 broiler males housed in 50 cages. The experimental design was based on the administration of a common corn-soybean meal nonsupplemented with additional IF sources diet in mash form (Control), and 4 dietary treatments consisting in the Control diet diluted with 1.5% of different IF: lignocellulose (LC), fine-ground straw (FS) and coarse-ground straw (CS), all characterized by high HC; and almond shell (AS) having low HC. Cecal fermentation was assessed by in vitro fermentation of the IF sources using the cecal content of 22-day broilers as inoculum. Compared with control birds, the inclusion of IF sources tended to impair the FCR (P=0.053), with birds fed the HC-IF sources (LC, FS, and CS) showing lower ADFI (P=0.005) and ADG (P=0.001) than those fed the AS diet. The relative weight of gizzard and cecum, small intestine length, and digestive transit time decreased in AS group (P ≤ 0.050) compared with the average value of the groups fed the other IF sources. The inclusion of IF reduced (P=0.006) the excreta moisture content, with no differences among IF sources. Dietary treatments had no effect either on cecal short fatty acids concentration or on intestinal morphology. As indicated by the in vitro gas production results, both LC and AS were less fermented than FS and CS, although all IF sources were low fermentable. None of the IF sources were able to influence the fermentation capacity of cecal microbiota after 22 d of feeding. In summary, animals fed AS presented smaller gizzard and cecum relative size, showed higher ADFI and ADG, and tended to improve fed conversion ratio in comparison to those fed the rest of IF sources.

5-HT4 Receptor is Protective for MPTP-induced Parkinson's Disease Mice Via Altering Gastrointestinal Motility or Gut Microbiota.

Serotonergic dysfunction is related to both motor and nonmotor symptoms in Parkinson's disease (PD). As a 5-HT receptor, 5-HT4 receptor (5-HT4R) is well-studied and already-used in clinical therapy of constipation, which is a typical non-motor symptom in PD. In this study, we investigated the role of 5-HT4R as a regulator of gut function in MPTP-induced acute PD mice model. Daily intraperitoneal injection of GR 125487 (5-HT4R antagonist) was administered 3 days before MPTP treatment until sacrifice. Seven days post-MPTP treatment, feces were collected and gastrointestinal transit time (GITT) was measured, 8 days post-MPTP treatment, behavioral tests were performed, and then animals were sacrificed for the further analysis. We found GR 125487 pretreatment not only increased GITT, but also aggravated MPTP-induced motor bradykinesia. In addition, GR 125487 pretreatment exacerbated the loss of dopaminergic neurons probably by suppressing JAK2/PKA/CREB signaling pathway and increased reactive glia and neuroinflammation in the striatum. 16S rRNA sequencing of fecal microbiota showed that GR 125487 pretreatment altered the composition of gut microbiota, in which the abundance of Akkermansia muciniphila and Clostridium clostridioforme was increased, whereas that of Parabacteroides distasonis and Bacteroides fragilis was decreased, which are closely associated with inflammation condition. Taken together, we demonstrated that GR 125487 pretreatment exacerbates MPTP-induced striatal neurodegenerative processes possibly via the JAK2/PKA/CREB pathway and neuroinflammation by altering gut microbiota composition. In the microbiota-gut-brain axis of PD, 5-HT4R should be further explored and might serve as a target for PD diagnosis and treatment.

Bioinspired fine-tuning of the mechanical rigidity of SNEDDS for the efficient crossing of multiple gastrointestinal barriers

Nanoproperties, such as size, charge, and rigidity, have been demonstrated to be crucial for nanovehicles to overcome numerous gastrointestinal obstacles. However, the facile approach of modifying the rigidity of nanovehicles remains scarce, limiting understanding of how rigidity impacts their oral delivery. Inspired by the fact that cellular phospholipid content regulates plasma membrane rigidity, the rigidity of self-nanoemulsifiying drug delivery system (SNEDDS) could be fine-tuned via phosphocholine content while their size and zeta potential remain unchanged, using insulin as a model drug. Notably, soft SNEDDS exerted longer gastrointestinal transit time, higher drug release rate, stronger gastrointestinal stability and relatively lower mucus permeation but superior epithelial transcytosis than their hard counterparts in a macropinocytosis-dependent manner. The rigidity-related enhanced transcytosis was attributed to improved endocytosis, lysosome escape capability and exocytosis. Rats with type 1 diabetes exhibited greater oral insulin absorption and blood glucose lowering effect with soft SNEDDS. This study demonstrated the regulatory role of phospholipids in nanovehicle rigidity, which could help develop mechanically optimized nanomedicines in the future.

Gastrointestinal Transit Times in Health as Determined Using Ingestible Capsule Systems: A Systematic Review.

Ingestible capsule (IC) systems can assess gastrointestinal (GI) transit times as a surrogate for gut motility for extended periods of time within a minimally invasive, radiation-free and ambulatory setting. A literature review of IC systems and a systematic review of studies utilizing IC systems to measure GI transit times in healthy volunteers was performed. Screening for eligible studies, data extraction and bias assessments was performed by two reviewers. A narrative synthesis of the results was performed. The literature review identified 23 different IC systems. The systematic review found 6892 records, of which 22 studies were eligible. GI transit time data were available from a total of 1885 healthy volunteers. Overall, seventeen included studies reported gastric emptying time (GET) and small intestinal transit time (SITT). Colonic transit time (CTT) was reported in nine studies and whole gut transit time (WGTT) was reported in eleven studies. GI transit times in the included studies ranged between 0.4 and 15.3 h for GET, 3.3-7 h for SITT, 15.9-28.9 h for CTT and 23.0-37.4 h for WGTT. GI transit times, notably GET, were influenced by the study protocol. This review provides an up-to-date overview of IC systems and reference ranges for GI transit times. It also highlights the need to standardise protocols to differentiate between normal and pathological function.

Ultraprocessed Foods and Obesity Risk: A Critical Review of Reported Mechanisms.

Epidemiologic evidence supports a positive association between ultraprocessed food (UPF) consumption and body mass index. This has led to recommendations to avoid UPFs despite very limited evidence establishing causality. Many mechanisms have been proposed, and this review critically aimed to evaluate selected possibilities for specificity, clarity, and consistency related to food choice (i.e., low cost, shelf-life, food packaging, hyperpalatability, and stimulation of hunger/suppression of fullness); food composition (i.e., macronutrients, food texture, added sugar, fat and salt, energy density, low-calorie sweeteners, and additives); and digestive processes (i.e., oral processing/eating rate, gastric emptying time, gastrointestinal transit time, and microbiome). For some purported mechanisms (e.g., fiber content, texture, gastric emptying, and intestinal transit time), data directly contrasting the effects of UPF and non-UPF intake on the indices of appetite, food intake, and adiposity are available and do not support a unique contribution of UPFs. In other instances, data are not available (e.g., microbiome and food additives) or are insufficient (e.g., packaging, food cost, shelf-life, macronutrient intake, and appetite stimulation) to judge the benefits versus the risks of UPF avoidance. There are yet other evoked mechanisms in which the preponderance of evidence indicates ingredients in UPFs actually moderate body weight (e.g., low-calorie sweetener use for weight management; beverage consumption as it dilutes energy density; and higher fat content because it reduces glycemic responses). Because avoidance of UPFs holds potential adverse effects (e.g., reduced diet quality, increased risk of food poisoning, and food wastage), it is imprudent to make recommendations regarding their role in diets before causality and plausible mechanisms have been verified.

Enzyme-Triggered Intestine-Specific Targeting Adhesive Platform for Universal Oral Drug Delivery.

Patient adherence to chronic therapies can be suboptimal, leading to poor therapeutic outcomes. Dosage forms that enable reduction in dosing frequency stand to improve patient adherence. Variation in gastrointestinal transit time, inter-individual differences in gastrointestinal physiology and differences in physicochemical properties of drugs represent challenges to the development of such systems. To this end, a small intestine-targeted drug delivery system is developed, where prolonged gastrointestinal retention and sustained release are achieved through tissue adhesion of drug pills mediated by an essential intestinal enzyme catalase. Here proof-of-concept pharmacokinetics is demonstrated in the swine model for two drugs, hydrophilic amoxicillin and hydrophobic levodopa. It is anticipated that this system can be applicable for many drugs with a diverse of physicochemical characteristics.

Associations Between Physical Activity and Gastrointestinal Transit Times in People with Normal Weight, Overweight, and Obesity

BackgroundRapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood. ObjectiveThe objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity. Methods50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities—sedentary activity (0–100 counts/min), low light activity (101–759 counts/min), high light activity (760–1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times. ResultsMedian [Q1; Q3] age was 56.5 [46.6–65.5] y, and body mass index (BMI) was 32.1 [28.5–35.1] kg/m2. For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed. ConclusionsMore time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated. Trial registrationClinicaltrials.gov IDs (NCT03894670, NCT03854656).

Antidiarrheal coumarins from Psydrax schimperianus (A. Rich.) Bridson roots

Ethnopharmacological relevancePsydrax schimperianus (A. Rich.) Bridson. roots are used for the treatment of diarrhea in West Arsi zone, Ethiopia. Aim of the studyThis study aimed to investigate the in vivo antidiarrheal activity of crude extract and coumarins isolated from the roots of Psydrax schimperianus to provide a pharmacological basis for its traditional use as an antidiarrheal agent in Ethiopia. Materials and methodsThe crude root extract of P. schimperianus was tested in vivo for antidiarrheal efficacy in mice utilizing castor oil-induced diarrhea, gastrointestinal transit time, and enteropooling models at doses of 100, 200, and 400 mg/kg. Phytochemical investigation of the crude root extract led to the isolation of two coumarins, isoscopoletin, and scoparone. Isoscopoletin and scoparone were evaluated for antidiarrheal activity against castor oil-induced diarrhea model at 10 mg/kg and 20 mg/kg doses. ResultsThe crude root extract of P. schimperianus, at doses of 100, 200, and 400 mg/kg, inhibited defecation by 37.5%, 46.2%, and 61.2%, respectively. At a dose of 20 mg/kg, scoparone and isoscopoletin reduced defecation by 61.2% and 66.6%, respectively. ConclusionThe study warrants further investigation of isoscopoletin and scoparone towards development as a novel treatment for diarrheal diseases.