Small Intestinal Conditions Research Articles

Effect of chlorogenic acid on the structural properties and digestibility of lotus seed starch during microwave gelatinization

The structural evolution of lotus starch (LS)-chlorogenic acid (CA) complexes was investigated after microwave-heating treatment, to reveal the relationship between the interactions of lotus starch and chlorogenic acid molecules, and the digestive properties of the starch, after microwave gelatinization. During the early stage of microwave gelatinization (65, 70 °C), CA was mainly participating in the rearrangement of starch molecules in a weakly-bound form, and at that stage, the LS-CA complex acted as an inhibitor of digestion, under small intestine conditions, mainly through the release of CA, which inhibited amylase. However, during the late stage of microwave gelatinization (85 °C), many chlorogenic acid molecules entered the hydrophobic helical cavity of the starch, promoting formation of the V-type starch helical structure in the LS-CA complex, which made a major contribution to inhibiting digestion under oral digestion conditions.

Encapsulation of hydrophobic capsaicin within the aqueous phase of water-in-oil high internal phase emulsions: Controlled release, reduced irritation, and enhanced bioaccessibility

Capsaicin (CAP) is a hydrophobic substance with various physiological effects in chili peppers that is responsible for their perceived heat. Nonetheless, its application as a nutraceutical is hugely hindered by its low bioaccessibility and mucosal irritation. In this study, capsaicin was entrapped in the water phase of water-in-oil (W/O) high internal phase emulsions (HIPEs) using a pH-driven method. Initially, the capsaicin was mixed with sodium alginate (SA) to form a water-dispersible form of the capsaicin and then used to form CAP-loaded W/O HIPEs. The influence of capsaicin concentration on the properties of W/O HIPEs was then investigated. Cryo-SEM observation demonstrated a thick lipid shell formed around the water droplets and a dense network in the aqueous core. The addition of capsaicin caused an increase in the viscoelasticity of the HIPEs. The CAP-loaded HIPEs exhibited good stability and the capsaicin was shown to remain within the aqueous core (rather that moving to the oil phase) during storage. Only a relatively small amount of capsaicin leaked out of the HIPEs under simulated oral and gastric conditions, but it was progressively released under simulated small intestine conditions as the external lipid phase was digested by lipase. The bioaccessibility of capsaicin was greatly enhanced after encapsulation. An animal experiment showed that the CAP-loaded HIPEs reduced the irritation of the gastric mucosa. Our results suggest that W/O HIPEs may be a useful delivery system for active ingredients with undesirable flavor profiles and low bioaccessibilities.

Comparison of protection and release behavior of different capsule polymer combinations based on L. acidophilus survivability and function and caffeine release

Oral administration of active pharmaceutical ingredients, nutraceuticals, enzymes or probiotics requires an appropriate delivery system for optimal bioactivity and absorption. The harsh conditions during the gastrointestinal transit can degrade the administered products, hampering their efficacy. Enteric or delayed-release pharmaceutical formulations may help overcome these issues. In a Simulator of Human Intestinal Microbial Ecosystem model (SHIME) and using caffeine as a marker for release kinetics and L. acidophilus survivability as an indicator for protection, we compared the performance of ten capsule configurations, single or DUOCAP® combinations. The function of L. acidophilus and its impact on the gut microbiota was further tested in three selected capsule types, combinations of DRcaps® capsule in DRcaps® capsule (DR-in-DR) and DRcaps® capsule in Vcaps® capsule (DR-in-VC) and single Vcaps® Plus capsule under colonic conditions. We found that under stomach and small intestine conditions, DR-in-DR and DR-in-VC led to the best performance both under fed and fasted conditions based on the slow caffeine release and the highest L. acidophilus survivability. The Vcaps® Plus capsule however, led to the quickest caffeine and probiotic release. When DR-in-DR, DR-in-VC and single Vcaps® Plus capsules were tested through the whole gastrointestinal tract, including under colonic conditions, caffeine release was found to be slower in capsules containing DRcaps® capsules compared to the single Vcaps® capsules. In addition, colonic survival of L. acidophilus was significantly increased under fasted conditions in DR-in-DR or DR-in-VC formulation compared to Vcaps® Plus capsule. To assess the impact of these formulations on the microbial function, acetate, butyrate and propionate as well as ammonia were measured. L. acidophilus released from DR-in-DR or DR-in-VC induced a significant increase in butyrate and a decrease in ammonia, suggesting a proliferation of butyrate-producing bacteria and reduction in ammonia-producing bacteria. These data suggest that L. acidophilus included in DR-in-DR or DR-in-VC reaching the colon is viable and functional, potentially contributing to changes in colonic microbiota composition and diversity.

Tips for successful deep enteroscopy.

The aim of this study was to provide practical tips to readers on how to perform deep enteroscopy efficiently. Deep enteroscopy has revolutionized the diagnosis and management of small intestinal conditions in recent years. They are extremely valuable, but may be technically challenging to perform, regardless if it is double balloon enteroscopy, single balloon enteroscopy or spiral enteroscopy. The common issues to these procedures are repetitive motion, extended procedure duration and physical exertion during scope advancement. These situations may in turn lead to a variety of ergonomic issues that need to be addressed accordingly to prevent occupational injuries to the endoscopists and their assistants. Depending on the clinical indications, the technical approach and execution of these procedures may be carried out differently. Some guiding principles may be applied to make performing these procedures more smoothly, effectively and deeply. Careful planning and skilful manipulations are essential to performing an efficient and stress-free deep enteroscopy. There are many simple ways to improve on the ergonomics and performance of these procedures.

Utilization of sonication-glycation to improve the functional properties of ovalbumin: A high-resolution mass spectrometry study

Ovalbumin (OVA) is a globular protein found in hen's eggs that has excellent nutritional and functional properties but is a major allergen. Previous studies have shown that ultrasound pretreatment combined with glycation (sonication-glycation) of OVA markedly reduced its IgG and IgE binding capacities and enhanced its antioxidant activity. In this study, the effects of sonication-glycation on a number of important functional attributes of OVA were studied: foaming, emulsifying, and digestibility. These processes significantly enhanced the foaming and emulsifying properties of OVA by increasing the exposure of hydrophobic residues at the protein surfaces. Moreover, reversed-phase chromatography indicated that sonication-glycation only caused a small decrease in OVA digestibility under simulated gastric and small intestine conditions, and that the level of IgG and IgE binding of OVA was exceedingly low after digestion. Furthermore, sonication promoted the glycation of OVA by increasing the number of exposed glycation sites, as determined by high-resolution mass spectrometry. These results imply that sonication-glycation is a promising method for improving the functional performance of food proteins, while also reducing their immunogenicity.

Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability

Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.

Vedolizumab for the Treatment of Noninflammatory Bowel Disease Related Enteropathy

Vedolizumab has become an integral part of the therapeutic armamentarium for patients with inflammatory bowel disease (IBD) who have failed conventional medical therapy. Vedolizumab is an α4β7 integrin antagonist that inhibits intestinal T-cell translocation by blocking integrin interactions with mucosal vascular addressin cellular adhesion molecule 1, reducing lymphocyte-mediated inflammation.1 Its gut selective mode of action and favorable safety profile have led to reports of off-label use for non-IBD-related inflammatory intestinal disorders, such as microscopic colitis,2 and small intestinal inflammatory conditions including autoimmune enteropathy3 and common variable immune deficiency-related enteritis.4 Treatment of non-IBD-related enteropathies is challenging with no approved therapies or established treatment algorithms. We conducted a literature review to assess clinical, endoscopic, and histologic improvement in patients treated with vedolizumab for non-IBD enteropathies refractory to conventional therapy.

Role of Biorelevant Media in the Estimation of In Vitro Lipolysis and Food Impact on Self-emulsifying Drug Delivery Systems

Self-emulsifying drug delivery systems (SEDDS) include self-microemulsifying drug delivery system (SMEDDS) and self-nanoemulsifying drug delivery system (SNEDDS) whose major benefits are reduction of inter/intrasubject variability and food effect that results in a better pharmacological response of the drug. Oral intake of these formulations triggers the digestion process because of pancreatic lipase which emulsifies/digests the lipidic ingredients of the formulation leading to precipitation of the drug. As a tool to foresee in vivo medicament precipitation, in vitro lipolysis models are established. Biorelevant media play an important role to study the effect of in vitro lipolysis and food impact on the bioavailability of SEDDS formulations. It is vital to generate the composition of fluids for both fed and fasting conditions of gastric, small intestine and colon to investigate the impact of in vitro lipolysis and food on drug’s release behavior from the formulation. Fed/Fasted state simulated gastric fluid (Fe/FaSSGF), and Fed/Fasted state simulated gastric fluid (Fe/FaSSIF) (Phosphate buffers) are first-generation. While Fa/FeSSIF-V2 (maleate) are second- generation biorelevant media utilized for these studies. FaSSIF-V3 belongs to the thirdgeneration which differs from other generations in the composition and source of bile salts. With updates in physiological data, it is vital to incorporate changes in dissolution media composition to make it more biorelevant. This review paper mainly emphasized the compositions of biorelevant media of gastric and small intestine for both fed and fasting conditions. Besides, applications of biorelevant media to investigate the effect of in vitro lipolysis and food on SEDDS are discussed with some recent research reports.

Encapsulation of bifidobacterium in alginate microgels improves viability and targeted gut release

Biopolymer microgels were designed to encapsulate and protect probiotics during storage and passage through the upper human gastrointestinal tract (GIT), but then release them in the colon. An anaerobic probiotic strain (Bifidobacterium pseudocatenulatum G7; BPG7) was encapsulated within calcium alginate microgels. In some cases, either colloidal antacid (CaCO3) or colloidal antacid and nanoemulsion (nE) lipid droplets were co-encapsulated with the probiotics. These additives were used to control the porosity and/or internal pH of the microgels. Initially, the viability of free and encapsulated probiotics was evaluated when they were stored at 4 °C for 28 days. The free probiotics rapidly degraded during storage.Encapsulation greatly improved the stability of the probiotics, with the effectiveness depending on the formulation: antacid-microgels > control microgels > antacid-nE-microgels. These effects were mainly attributed to the ability of the colloidal CaCO3 particles to inhibit molecular diffusion processes. The ability of the microgels to protect the probiotics under simulated gastrointestinal tract (GIT) conditions was then assessed. The free probiotics were completely inactivated when exposed to gastric and small intestine conditions. In contrast, the antacid- and antacid-nE-microgels were highly effective at improving the viability of the probiotics during passage through the upper GIT. Moreover, these microgels were fermented under simulated colonic conditions, thereby releasing the probiotics. These results suggest that antacid-loaded calcium alginate microgels can be used for the encapsulation, protection, and colonic delivery of probiotics. Nevertheless, further studies are required using in vivo models.

In vitro digestion of edible nanostructured lipid carriers: Impact of a Candelilla wax gelator on performance

In this study, food-grade nanostructured lipid carriers (NLCs) were used as delivery systems to overcome some of the limitations of solid lipid nanoparticles (SLNs) and liquid lipid nanoparticles (LLNs). Organogel NLCs were prepared using an oil phase consisting of a hydrophobic gelator (Candelilla wax) dispersed in liquid corn oil. The oil phase undergoes a gel-to-sol transition when heated, which means that oil-in-water nanoemulsions can be used as templates to form the NLCs. The impact of lipid phase composition on the gastrointestinal fate of the NLCs was determined using a simulated gastrointestinal tract (GIT). The particle size, ζ-potential, and microstructure of the LLNs, NLCs and SLNs were characterized when they were exposed to model oral, gastric, and small intestine conditions. The oil phase in the LLNs and SLNs consisted of pure corn oil and pure Candelilla wax, respectively. Initially, all samples contained small lipid particles (d43 = 150–202 nm) with negative surface potentials (ζ = −26 to −47 mV). The LLNs, SLNs and NLCs behaved similarly in the simulated GIT in terms of their particle properties: there was a large increase in particle size and decrease in charge magnitude in the mouth, stomach, and intestine. The Candelilla wax in the SLNs and NLCs was not digested by lipase, but the corn oil in the LLNs and NLCs was fully digested. This phenomenon may be used to create colloidal delivery systems that can control the release of encapsulated bioactive agents within the GIT.

Characterization of gastrointestinal transit and luminal conditions in pigs using a telemetric motility capsule

Within preclinical research, the pig has become an important model in regulatory toxicology and pharmacokinetics, to assess oral dosage forms and to compare different formulation strategies. In addition, there are emerging application of the pig model to asses clinical dosing conditions in the fasted and fed state. In this study, the gastrointestinal transit conditions in male landrace pigs were studied with a telemetric motility capsule under fasted and postprandial conditions. The whole gut transit time (WGTT) was determined by administering a SmartPill® capsule to four landrace pigs, under both fasted and fed state conditions in a cross-over study design. Overall, this study found that small intestinal transit in landrace pigs ranged from 2.3 – 4.0 h, and was broadly similar to reported human estimates and was not affected by the intake conditions. Gastric emptying was highly variable and prolonged in landrace pigs ranging from 20 – 233 h and up to 264 h in one specific case. Under dynamic conditions pigs have a low gastric pH comparable to humans, however a high variability under fasted conditions could be observed. The comparison of the data from this study with a recent similar study in beagle dogs revealed major differences between gastric maximum pressures observed in landrace pigs and dogs. In the porcine stomach maximum pressures of up to 402 mbar were observed, which are comparable to reported human data. Intestinal maximum pressures in landrace pigs were in the same range as in humans. Overall, the study provides new insights of gastrointestinal conditions in landrace pigs, which can lead to more accurate interpretation of in vivo results obtained of pharmacokinetic studies in preclinical models. While small intestinal transit conditions, GI pH and pressures were similar to humans, the prolonged gastric emptying observed in pigs need to be considered in assessing the suitability of the pig model for assessing in vivo performance of large non-disintegrated oral drug products.

In Vitro Digestion and Fermentation by Human Fecal Microbiota of Polysaccharides from Flaxseed.

The digestion of flaxseed polysaccharides (FSP) in simulated saliva, gastric and small intestine conditions was assessed, as well as in vitro fermentation of FSP by human gut microbiota. FSP was not degraded in the simulated digestive systems (there was no change in molecular weight or content of reducing sugars), indicating that ingested FSP would reach the large intestine intact. Changes in carbohydrate content, reducing sugars and culture pH suggested that FSP could be broken down and used by gut microbiota. FSP modulated the composition and structure of the gut microbiota by altering the Firmicutes/Bacteroidetes ratio and increasing the relative abundances of Prevotella, Phascolarctobacterium, Clostridium and Megamonas, which can degrade polysaccharides. Meanwhile, FSP fermentation increased the concentration of short-chain fatty acids, especially propionic and butyric acids. Our results indicate that FSP might be developed as a functional food that benefits gut health.

Digestion of animal- and plant-based proteins encapsulated in κ-carrageenan/protein beads under simulated gastrointestinal conditions

In this study, we encapsulated both animal-derived (whey) and plant-derived (soy and pea) proteins within polysaccharide/protein beads and measured the digestion of these beads under simulated gastrointestinal tract (GIT) conditions. Bead dimensions were measured using a digital caliper and found to increase as the shear thinning behavior of the protein/polysaccharide solutions used to form them increased. The hydrolysis of the plant and animal proteins trapped inside the protein/polysaccharide beads was studied using the pH-stat automatic titration method under simulated static GIT conditions. The encapsulated proteins were relatively resistant to digestion under gastric conditions, with only about 10 to 13% of the protein being digested by the end of the stomach phase. Conversely, they were almost fully digested under small intestinal conditions, with around 87 to 97% of the protein being hydrolyzed by the end. Indeed, by the completion of the small intestine phase, only “ghost” beads remained that contained cross-linked polysaccharides. The soy and pea proteins were digested slightly faster than the whey proteins in the stomach phase (p < 0.05), whereas the pea proteins were digested slightly faster than the soy and whey proteins under intestinal conditions (p < 0.05). Raman spectroscopy and scanning electron microscopy showed that there were changes in the composition and structure of the beads throughout the simulated GIT. Our results indicate that the gastrointestinal behavior of proteins can be modulated by encapsulating them in polysaccharide beads, which may be useful for the design of certain types of functional foods. Even so, the beads formed from the plant-based and animal-based proteins behaved fairly similarly, suggesting that animal proteins could be replaced by plant-based ones for this purpose.

Evaluation of the fate of Lactobacillus crispatus BC4, carried in Squacquerone cheese, throughout the simulator of the human intestinal microbial ecosystem (SHIME)

Lactobacillus crispatus strain BC4, isolated from the human healthy vaginal environment and characterised by a strong antimicrobial activity against urogenital pathogens and foodborne microorganisms, was employed as a probiotic culture in the cheesemaking of the soft cheese Squacquerone. Such cheese is intended as a “gender food”, that could be used as a hedonistic dietary strategy to reduce the incidence of woman vaginal dysbiosis and infections, given the evidence that a probiotic strain able to survive to the entire digestive process once ingested, can pass from intestine to vagina. This work was aimed to evaluate the resistance of L. crispatus BC4, carried in Squacquerone cheese, to different challenges of the human gastrointestinal tract, including the colon stage. The digestion process was tested using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). The viability and metabolic activity of L. crispatus BC4 during the colon simulation were monitored by qPCR and gas chromatography, respectively, also in the presence of a complex microbiota. The results showed that L. crispatus BC4 survival was not affected by the gastric condition, while it was significantly affected by bile salts and pancreatic juice in small intestine conditions, where it decreased of approx. 0.6 log (colony-forming units) CFU/g. Differently, during colon simulation L. crispatus BC4 was able to grow in sterile colon conditions and to maintain viability in the presence of a complex microbiota. Moreover, during colon simulation, L. crispatus BC4 was metabolically active as demonstrated by the higher production of short chain fatty acids (SCFA) and lactate. In the presence of a complex gut microbiota, a decrease of lactate was observed, due to its conversion into propionate (anti-cholesterol activity) and butyrate (anti-inflammatory activity) by cross-feeding. However, no differences in propionate and butyrate production could be observed between control cheese and cheese containing L. crispatus BC4. Despite this may appear as a negative outcome, it must be taken into account that, in this setup, only a single dose of the cheese was tested and the outcome of the colonization and impact of the gut microbiota might be different when daily repeated doses are tested.

In vitro Fermentation of Digested Milk Fat Globule Membrane From Ruminant Milk Modulates Piglet Ileal and Caecal Microbiota.

Lipids in milk are secreted as a triacylglycerol core surrounded by a trilayer membrane, the milk fat globule membrane (MFGM). This membrane, known to have important roles in infant brain and intestinal development, is composed of proteins, glycoproteins, and complex lipids. We hypothesized that some of the beneficial properties of MFGM are due to its effects on the gastrointestinal microbiota. This study aimed to determine the effect of a commercial phospholipid concentrate (PC) and enriched bovine, caprine, and ovine MFGM fractions on ileal and hindgut microbiota in vitro. Digestion of PC and MFGMs was conducted using an in vitro model based on infant gastric and small intestine conditions. The recovered material was then in vitro fermented with ileal and caecal inocula prepared from five piglets fed a commercial formula for 20 days before ileal and caecal digesta were collected. After each fermentation, samples were collected to determine organic acid production and microbiota composition using 16S rRNA sequencing. All substrates, except PC (5%), were primarily fermented by the ileal microbiota (8–14%) (P < 0.05). PC and caprine MFGM reduced ileal microbiota alpha diversity compared to ileal inoculum. Caprine MFGM increased and PC reduced the ileal ratio of firmicutes:proteobacteria (P < 0.05), respectively, compared to the ileal inoculum. Bovine and ovine MFGMs increased ileal production of acetic, butyric, and caproic acids compared to other substrates and reduced the proportions of ileal proteobacteria (P < 0.0001). There was a limited fermentation of bovine (3%), caprine (2%), and ovine (2%) MFGMs by the caecal microbiota compared to PC (14%). In general, PC and all MFGMs had a reduced effect on caecal microbiota at a phylum level although MFG source-specific effects were observed at the genus level. These indicate that the main effects of the MFGM in the intestinal microbial population appears to occur in the ileum.

Redox-Sensitive Linear and Cross-Linked Cystamine-Based Polymers for Colon-Targeted Drug Delivery: Design, Synthesis, and Characterisation.

Cystamine-based polymers may help to achieve controlled and targeted drug delivery to the colon due to their susceptibility to breakage of the disulfide linkage in the low redox potential environment of the colon. In this study, two linear cystamine-based polymers with similar repeating units (LP1 and LP2) and a cross-linked cystamine-based polymer (BP) were synthesised and their kinetics and the various physical conditions underlying cystamine-based polymerisation were evaluated. In brief, N1,N6-bis(2-(tritylthio)ethyl)adipamide (2) was synthesised from the reaction of triphenylmethanol and cysteamine. Next, the trityl group of 2 was removed with trifluoroacetic acid and triethylsilane before proceeding to oxidative polymerisation of the end product, N1,N6-bis(2-mercaptoethyl)adipamide (3) to LP1. The Schotten-Bauman reaction was applied to synthesise LP2 and BP from the reaction of cystamine with adipoyl chloride or trimesoyl chloride. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and mapping showed that oxygen, nitrogen, sulfur, and carbon were homogenously distributed in the polymers, with LP2 and BP having less porous morphologies compared to LP1. Results of zinc-acetic acid reduction showed that all polymers began to reduce after 15 min. Moreover, all synthesised polymers resisted stomach and small intestine conditions and only degraded in the presence of bacteria in the colon environment. Thus, these polymers have great potential for drug delivery applications. LP2 and BP, which were synthesised using the Schotten-Bauman reaction, were more promising than LP1 for colon-targeted drug delivery.

Celiac disease: Biochemical and histopathological considerations of local patients

Background: Celiac disease (CD) is a chronic small intestinal condition caused by immune-mediated pathology, which is due to the prolonged deficiency of gluten in genetically susceptible people and induced by the ingestion of a complex protein, gluten, found in cereals such as barley, wheat, and rye. Objectives: This study aimed to identify the frequency of individuals affected by CD in Duhok city and the impact of certain environmental factors on the disease occurrence. Materials and Methods: The current study was conducted in the Duhok central public health laboratory in Duhok/Kurdistan region/Iraq. This study involved 500 intestinal biopsy samples from which 34 biopsies diagnosed as having CD characteristics by histopathological examination performed by specialists in Duhok central public health laboratory. This finding was also supported by serological testing results using the tissue transglutaminase assay (tTG-IgA). Results: The results revealed that female CD patients exceeded male CD patients and represented by 24 (70.6%) and 10 (29.4%), respectively. Furthermore, a total of 18 (52.9%) individuals affected by CD were born in summer and spring months, while 16 (47.1%) subjects were born in fall and winter months. Our work also showed that subjects who had clinical presentation indicating and/or referring to risk factors for developing CD and tested positive for anti-TTG antibodies had a greater probability of manifesting duodenal damage and an ultimate diagnosis of the disease. The result of this study showed that the percentage of breastfed patients was 22 (64.7%) and cow milk-fed patients were 4 (11.8%), five (14.7%) patients were breastfed for = 6 months, and 3 (8.8%) patients were fed both. Conclusion: Histopathological and serological assays have powerful diagnostic potential, and one can potentiate the results of others. Environmental risk factors can determine the rate and intensity of the condition.

In vitro Gastrointestinal Models for Prebiotic Carbohydrates: A Critical Review.

In the last decade, various consortia and companies have created standardized digestion protocols and gastrointestinal simulators, such as the protocol proposed by the INFOGEST Consortium, the simulator SHIME, the simulator simgi®, the TIM, etc. Most of them claim to simulate the entire human gastrointestinal tract. However, few results have been reported on the use of these systems with potential prebiotic carbohydrates. This critical review addresses the existing data on the analysis of prebiotic carbohydrates by different in vitro gastrointestinal simulators, the lack of parameters that could affect the results, and recommendations for their enhancement. According to the reviewed data, there is a lack of a realistic approximation of the small intestinal conditions, mainly because of the absence of hydrolytic conditions, such as the presence of small intestinal brush border carbohydrases that can affect the digestibility of different carbohydrates, including prebiotics. There is a necessity to standardize and enhance the small intestine simulators to study the in vitro digestibility of carbohydrates.

The mechanism of solifenacin release from a pH-responsive ion-complex oral suspension in the fasted upper gastrointestinal lumen

The main objective of this study was to investigate the mechanism of solifenacin release from a pH-responsive ion-complex oral resinate suspension under conditions simulating the environment in the upper gastrointestinal lumen. A secondary objective was to propose an appropriate in vitro methodology for evaluating the quality of orally administered solifenacin suspensions. The mechanism of solifenacin release from polacrilin potassium resin (Amberlite® IRP88) was investigated using biorelevant media and compendial setups (USP Apparatus 2 and USP Apparatus 4) and using newer, recently validated in vitro methodologies [biorelevant gastrointestinal transfer (BioGIT) system]. We evaluated the impact of particle size and concentration of the resin; thickener concentration (carbomer homopolymer, type B); and the impact of pH, cationic strength, agitation intensity and level of simulation of contents in the upper gastrointestinal lumen. Data suggested that solifenacin release from the resinate was determined by the resin particle size, the medium pH, cationic strength (when the conditions in the upper small intestine are simulated) and the level of simulation of contents in the upper small intestine. The interaction of solifenacin with taurocholic acid/lecithin aggregates was significant, but unlikely to affect the degree of solifenacin absorption, as a BCS Class I compound. Under acidic conditions, solifenacin was dissociated and released from the pH-responsive resin rapidly. Under conditions simulating the contents of the upper small intestine, solifenacin was replaced by cations from the testing media and diffused through the resin matrix. All three in vitro systems with or without a pH gradient are useful in distinguishing solifenacin release characteristics from resinate suspensions with different particle sizes. Because of this drug release mechanism, USP Apparatus 2 with fixed pH media demonstrated equivalent or slightly higher discriminative sensitivity than the other setups and appears to be appropriate for product quality control.

Simulated digestion and fermentation in vitro by human gut microbiota of polysaccharides from Helicteres angustifolia L

Helicteres angustifolia L. is a familiar herbal plant, which exhibits various bioactivities with potential benefits for human health. In this study, the simulated digestion (saliva, simulated gastric and small intestinal conditions) and fermentation in vitro of polysaccharides from H. angustifolia L. (HaLPs) were evaluated, and the effects of HaLPs on gut microbiota were examined using high-throughput sequencing technology. The results indicated that the simulated gastrointestinal digestion had no effect on HaLPs, so HaLPs could reach the large intestine safely. However, the molecular weight of HaLPs and the reducing sugar decreased significantly after fermentation under anaerobic conditions. It was found that HaLPs had the significantly alternation effect on the composition of the gut microbiota. Furthermore, the total short-chain fatty acids content increased significantly after fermentation (from 2.25 ± 0.13 mM to 22.45 ± 4.56 mM). These results provided an understanding of the digestive characteristics of HaLPs and afforded a viable basis for their development.