Gastrointestinal Simulation Research Articles

Simplified Upper Gastrointestinal Endoscopic Simulator Made by Recycled Materials Could Be a Useful Tool of Education: Focus Group Interview

Simplified Upper Gastrointestinal Endoscopic Simulator Made by Recycled Materials Could Be a Useful Tool of Education: Focus Group Interview

The preparation of felodipine/zein amorphous solid dispersions and in vitro evaluation using a dynamic gastrointestinal system

ABSTRCT Felodipine has been widely used as a poorly water-soluble model drug for various studies to improve its oral bioavailability and in vivo efficacy. In this study, we developed amorphous solid dispersions (ASDs) via spray drying to enhance the bioavailability of felodipine through using natural zein protein as a novel polymeric excipient. The solid state characterization results demonstrated a single glass transition temperature (Tg ) around 128.6 °C and good physical stability post 3 months accelerated study under the condition of 40 °C and 75% relative humidity (RH), which is possibly accounted for the molecular immobilization and hydrogen bonding interactions between felodipine and zein. By combining the in vitro dissolution study with TIM-1 gastrointestinal simulation investigation, it is indicated that felodipine was rapidly released from the ASD in 30 mins, and the supersaturation of felodipine was well maintained over 6 h, which resulted in a significant enhancement of felodipine bioavailability during simulated digestive processes in the upper GI tract. This study suggests that spray drying combined with natural excipient zein is an efficient formulation strategy for the development of ASDs with enhanced aqueous solubility and bioavailability.

The ability of lactic acid bacteria strains to remove di‐n‐butyl phthalate in simulated food matrices

SummaryIn this study, DBP (Di‐n‐butyl phthalate) was used as an example to evaluate the plasticiser‐binding ability of lactic acid bacteria strains (LABs). Three strains of Lactobacillus plantarum 121, Leuconostoc mesenteroides DM12 and Lactobacillus acidophilus NCFM were selected from LABs to test their DBP binding ability in different simulated food matrices. The results indicated that starch, gelatinised starch and glucose could significantly promote the DBP binding efficiencies of LABs. Low‐concentration proteins (<5%) increased the binding rates. However, denatured protein had no significant effect on the DBP binding ability. On the contrary, amino acids reduced the binding rates. AFM detection results indicated that the cell morphology of LAB binding with DBP had no change after treated in gastrointestinal digestive simulation systems. Collectively, the LABs could be employed as a biological detoxification agent for human and animals by eliminating plasticiser from foods, feeds and digestive tract in the future.

High stability of plant-expressed virus-like particles of an insect virus in artificial gastric and intestinal fluids

The harsh conditions of the gastro-intestinal (GI) milieu pose a major barrier to the oral delivery of protein nanocages. Here we studied the stability of Nudaurelia capensis omega virus (NωV) virus-like particles (VLPs) in simulated GI fluids. NωV VLPs capsids and procapsids were transiently expressed in plants, the VLPs were incubated in various simulated GI fluids and their stability was determined by gel electrophoresis, density gradient ultracentrifugation and transmission electron microscopy (TEM). The results showed that the capsids were highly resistant to simulated gastric fluids at pH ≥ 3. Even under the harshest conditions, which consisted of a pepsin solution at pH 1.2, NωV capsids remained assembled as VLPs, though some digestion of the coat protein occurred. Moreover, 80.8% (±10.2%) stability was measured for NωV capsids upon 4 h incubation in simulated intestinal fluids. The high resistance of this protein cage to digestion and denaturation can be attributed to its distinctively compact structure. The more porous form of the VLPs, the procapsid, was less stable under all conditions. Our results suggest that NωV VLPs capsids are likely to endure transit through the GI tract, designating them as promising candidate protein nanocages for oral drug delivery.

Biosynthesis of Quercetin Palmitate Esters and Evaluation of their Physico‐Chemical Properties and Stability

AbstractQuercetin was acylated with palmitic acid, catalyzed by either Candida antarctica lipase B (CAL‐B) or Pseudomonas cepacia lipase C (PCL‐C) to produce quercetin palmitate esters. The effects of various operating factors including incubation temperature, reaction duration, and molar ratio of substrates on the bioconversion yield, initial rate of reaction, and regioselectivity of the reactions were investigated. Three new esters were identified: quercetin 4′‐palmitate (C31H40O8, 540 g mol−1), quercetin 3′,4′‐dipalmitate (C47H70O9, 778 g mol−1), and quercetin 7,3′,4′‐tripalmitate (C63H100O10, 1016 g mol−1). The effects of incubation temperature, reaction duration, and molar ratio of substrates on bioconversion yields varied across the conditions. However, the highest bioconversion yield of 27.72 ± 1.64% was obtained with PCL‐C, at day 7, incubation temperature of 60 °C, quercetin:palmitic acid molar ratio of 1:20. The initial rate of reaction was significantly higher with PCL‐C. However, regioselectivity was similar for both PCL‐C‐ and CAL‐B‐catalyzed reactions with acylation occurred successively at 4´‐OH, 3´‐OH, and 7‐OH. Thin‐layer chromatography analysis showed that the three quercetin palmitate esters possessed enhanced lipophilicity (134% higher than quercetin). Besides, in silico investigation showed that quercetin 4′‐palmitate had a higher partition coefficient (log P) value than the parent compounds, indicating improved solubility. During gastrointestinal tract simulation, quercetin palmitate esters were recovered in the range of 71.03% to 79.36% after digestion, which were significantly higher than quercetin at 40.43 ± 8.71%. Quercetin 4′‐palmitate was also found stable over 28 days of storage. Due to improved lipophilicity, solubility, and stability, quercetin 4′‐palmitate has the potential to be used in topical applications.

Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion.

Immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 μm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.

Chicken breast-derived alcohol dehydrogenase-activating peptides in response to physicochemical changes and digestion simulation: The vital role of hydrophobicity

Chicken breast muscle hydrolysates (CBMHs) could promisingly activate alcohol dehydrogenase (ADH) and ameliorate alcohol-induced liver injury. The aim of this work was to investigate the stability of CBMHs against physicochemical treatments and gastrointestinal digestion simulation. Results indicated that CBMHs showed good stability towards heating (25–121 °C), pH treatment (pH 2–12) and remained stable in the presence of NaCl (0.01–2 M) and low concentration of metal ions (0.1 mM Zn2+, Ca2+, Fe2+, and Fe3+). Results from in vitro digestion implied a retained activity of CBMHs after gastric tract, but marked decrease (33.42%) after intestinal tract. UPLC-ESI-Q-ToF-MS/MS analysis together with in silico assessments then revealed that the degradation of hydrophobic peptides (i.e., VAPEEHPTLL, YPGIADRM, ADGPLKGIL, and KDLFDPVIQ) during simulated intestinal digestion may be account for the decreased activity. Conformational changes of ADH upon hydrophobic interaction with synthetic peptides were further confirmed by fluorescence quenching study, possibly responsible for the enhanced ADH activity. Hence, CBMHs noticeably showed good stability against physicochemical treatments and digestion simulation, while attempt establishing the structure–activity relationship of peptides is also fundamental before applying CBMHs as functional ingredient.

Technical feasibility of a newly designed bendable forceps for difficult endoscopic tissue samplings (with video).

Biopsies with conventional forceps beyond the operating range are difficult and cumbersome. Thus, we developed a new bendable forceps for improved access to gastrointestinal lesions and evaluated its technical feasibility. A bendable forceps was constructed with two channels and a two-stage knob. The bending motion-related structures were designed to improve the range of motion. For the evaluation of the forceps, we used 2 gastrointestinal simulators: an ex vivo porcine model, and an in vivo porcine model with some difficult endoscopic biopsy cases. All evaluations were performed by 5 expert endoscopists and an expert pathologist. Compared with the conventional forceps, the bendable forceps had greater efficacy in the simulator (6.2±0.4 vs. 1.96±0.2, p<0.001), ex vivo porcine model (6.33±0.52 vs. 4.25±0.89, p<0.001), and in vivo porcine model (6.33±0.52 vs. 4.25±0.89, p<0.001); greater safety in the simulator (1.92±0.13s vs. 4.88±0.50s, p<0.001), ex vivo porcine model (2.02±0.15s vs 4.66±0.27s, p<0.001), and in vivo porcine model (2.02±0.15s vs. 4.08±0.70s, p=0.002); and larger specimens in the ex vivo porcine model (3.92±0.03mm vs. 3.85±0.07mm, p=0.020). This study showed that compared with the conventional forceps, the bendable forceps was effective and safe to use for accessing difficult lesions in the three models. We believe that the bendable forceps serves as a useful supplementary diagnostic tool for accessing difficult lesions. However, further validation of its usefulness in the human body is needed.

Development of orally administered insulin-loaded polymeric-oligonucleotide nanoparticles: statistical optimization and physicochemical characterization

Introduction Therapeutic peptides are administered via parenteral route due to poor absorption in the gastrointestinal (GI) tract, instability in gastric acid, and GI enzymes. Polymeric drug delivery systems have achieved significant interest in pharmaceutical research due to its feasibility in protecting proteins, tissue targeting, and controlled drug release pattern. Materials and methods In this study, the size, polydispersity index, and zeta potential of insulin-loaded nanoparticles were characterized by dynamic light scattering and laser Doppler micro-electrophoresis. The main and interaction effects of chitosan concentration and Dz13Scr concentration on the physicochemical properties of the prepared insulin-loaded nanoparticles (size, polydispersity index, and zeta potential) were evaluated statistically using analysis of variance. A robust procedure of reversed-phase high-performance liquid chromatography was developed to quantify insulin release in simulated GI buffer. Results and discussion: We reported on the effect of two independent parameters, including polymer concentration and oligonucleotide concentration, on the physical characteristics of particles. Chitosan concentration was significant in predicting the size of insulin-loaded CS-Dz13Scr particles. In terms of zeta potential, both chitosan concentration and squared term of chitosan were significant factors that affect the surface charge of particles, which was attributed to the availability of positively-charged amino groups during interaction with negatively-charged Dz13Scr. The excipients used in this study could fabricate nanoparticles with negligible toxicity in GI cells and skeletal muscle cells. The developed formulation could conserve the physicochemical properties after being stored for 1 month at 4 °C. Conclusion The obtained results revealed satisfactory results for insulin-loaded CS-Dz13Scr nanoparticles (159.3 nm, pdi 0.331, −1.08 mV). No such similar study has been reported to date to identify the main and interactive significance of the above parameters for the characterization of insulin-loaded polymeric-oligonucleotide nanoparticles. This research is of importance for the understanding and development of protein-loaded nanoparticles for oral delivery.

Assessment of in vitro bioacessibility of macrominerals and trace elements in green banana flour

The in vitro gastrointestinal simulation allows estimating the bioaccessible fraction (BF), thus indicating the real nutritional food value. Most studies that use in vitro tests assess the antioxidant capacity of foods, however, the bioaccessibility of elements is still little explored, mainly in functional foods, as the green banana flour (GB). Therefore, this paper describes the total concentration and BF of Mg, Ca, Zn, Mn, Cu and Fe in different brands of GB flours. The chemical composition and phytic acid (PA) concentration were also determined. In general, the highest concentrations (mg 100 g−1) of the total mineral were obtained for Mg (99.2–161) > Ca (27.9–74.7) > Fe (2.6–11). The highest gastrointestinal BF (%) were obtained for Mg (84–101), Mn (80–85), Cu (70–87) and Zn (76–92). The elements that were directly affected by the presence of PA were Ca and Fe, with BF ranging from 24 to 34 % and 21–35 %, respectively, most likely due to the formation of insoluble complexes in the conditions of the gastrointestinal tract. According to achieved results, based on total concentration, proximate composition and bioacessibility of elements, GB can provide an adequate intake of Mg, Cu, Fe and proteins, making its inclusion in the daily diet of great relevance.

Effects of Dietary Supplements on the Bioaccessibility of Se, Zn and Cd in Rice: Preliminary Observations from In Vitro Gastrointestinal Simulation Tests.

Trace elements such as selenium (Se) and zinc (Zn) are essential elements in the human body, while cadmium (Cd) has no physiological function. A high proportion of people consume dietary supplements to enhance the performance of the body or alter the nutrient contents within the body. Therefore, this study was conducted to evaluate the interaction effects of several popular dietary supplements on the bioaccessibility of Se, Zn and Cd in rice with the hope of identifying dietary supplements that can increase rice Se and Zn bioaccessibility but decrease rice Cd bioaccessibility. The results from in vitro gastrointestinal simulation tests showed that the bioaccessibility of these elements in rice was in the order of Cd (52.07%) > Zn (36.63%) > Se (10.19%) during the gastric phase and Zn (26.82%) > Cd (18.72%) > Se (14.70%) during the intestinal phase. The bioaccessibility of Se during the intestinal phase was greater than that during the gastric phase, and the bioaccessibility of Zn and Cd were the opposite. The bioaccessibility of Se significantly increased in response to vitamin C (VC), vitamin E (VE), vitamin B6 (VB6) and vitamin B9 (VB9), especially VC, which also increased the bioaccessibility of Zn and decreased that of Cd. Procyanidins (OPC), methionine (Met) and coenzyme Q10 (Q10) significantly reduced the bioaccessibility of Se. These results suggest that the reasonable use of dietary supplements can effectively regulate the in vivo contents of trace elements, which provide valuable information for developing health interventions to address problems for specific people, especially selenium-deficient people.

Egg yolk protein as a novel wall material used together with gum Arabic to encapsulate polyphenols extracted from Phoenix dactylifera L pits

In this study, previously delipidated egg yolk protein (EYP) was tested as a novel wall material, together with gum Arabic (GA), for encapsulating Phoenix dactylifera L (date) pit polyphenols. For this purpose, polyphenols were encapsulated by freeze-drying using different ratios of GA and EYP. Moisture content, color, microstructure of the powders, thermo-gravimetric analyses (TGA), encapsulation efficiency, antioxidant activity and an in vitro gastrointestinal simulation were carried out. An increase in the proportion of EYP produced a slight increase in the moisture content of the microparticles and higher ΔE values when the polyphenols were incorporated, but their morphology remained similar independently of the concentration of EYP tested. Furthermore, the microparticles containing a higher amount of EYP showed better thermal stability, higher encapsulation efficiency and better antioxidant properties. Finally, the in vitro gastrointestinal simulation study showed that a higher concentration of EYP than GA resulted in an improvement in the resistance of the microparticles to gastric and intestinal fluids. Overall, the EYP showed certain promising properties when it was used to encapsulate polyphenols.

Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b).

In the present work, we explored if Coca-Cola® had a beneficial impact on the systemic outcome of the weakly basic drug loratadine (Wal-itin®, immediate-release formulation, 10 mg, generic drug product). To map the contribution of underlying physiological variables that may positively impact the intestinal absorption of loratadine, a multi-compartmental and dynamic dissolution device was built, namely the Gastrointestinal Simulator (GIS). The luminal behavior of one immediate-release (IR) tablet of 10 mg of loratadine was tested under four different fasted state test conditions in the GIS: (i) with 250 mL of water and applying a predetermined gastric half-life (t1/2,G) of 15 min; (ii) with 250 mL of water and applying a t1/2,G of 30 min; (iii) with 250 mL of Coca-Cola® and a t1/2,G of 15 min; (iv) with 250 mL of Coca-Cola® and a t1/2,G of 30 min. After initiating the experiments, solution concentrations and solubility were measured in the withdrawn samples, and pH was monitored. To address the impact of the present CO2 in Coca-Cola® on the disintegration time of the tablet, additional disintegration experiments were performed in a single-vessel applying tap water and sparkling water as dissolution media. These experiments demonstrated the faster disintegration of the tablet in the presence of sparkling water, as the present CO2 facilitates the release of the drug. The buffer capacity of Coca-Cola® in the presence of FaSSGF was 4-fold higher than the buffer capacity of tap water in the presence of FaSSGF. After performing the in vitro experiments, the obtained results were used as input for a two-compartmental pharmacokinetic (PK) modeling approach to predict the systemic concentrations. These simulations pointed out that (i) the present CO2 in Coca-Cola® is responsible for the enhancement in drug release and dissolution and that (ii) a delay in gastric emptying rate will sustain the supersaturated concentrations of loratadine in the intestinal regions of the GI tract, resulting in an enhanced driving force for intestinal absorption. Therefore, co-administration of loratadine with Coca-Cola® will highly likely result in an increased systemic exposure compared to co-administration of loratadine with tap water. The mechanistic insights that were obtained from this work will serve as a scientific basis to evaluate the impact of Coca-Cola® on the systemic exposure of weakly basic drugs for patients on acid-reducing agents in future work.

Evaluation of antiproliferative and anti-inflammatory effects of non-pomace sediment of red grape juices (Vitis labrusca L.) in healthy and cancer cells after in vitro gastrointestinal simulation

Grape polyphenols are studied for their bioactive activities and health benefits. Grape juice clarification produces a colored non-pomace solid residue that is rich in polyphenols and may have potential for nutraceutical applications. This study therefore firstly investigated antiproliferative and anti-inflammatory properties of the non-pomace sediment of Bordo and Isabel grape juices before and after the gastrointestinal simulation, and evaluated the effects of the main individual phenolic compounds found in these sediments in regards to their antiproliferative action in healthy and cancer cells. The non-pomace sediments inhibited significantly the proliferation of colorectal adenocarcinoma cells (Caco-2) cells, whereas their digested fractions inhibited proliferation of hepatocellular carcinoma (HepG2) cells. However, the exposure to treatments caused no cell toxicity to healthy cells. When tested individually, the phenolic compounds quercetin and myricetin showed antiproliferative activity and led to cell viability of 56.47 and 51.07 % in Caco-2 cells and of 33.96 and 27.03 % in HepG2 cells, respectively. The non-pomace sediments and its digested fractions exhibited anti-inflammatory action by inhibiting the release of tumor necrosis factor alpha (TNF-α) in murine macrophages. These encouraging data suggests the potential use of this residue as dietary supplement or as a promising chemotherapy for antitumor therapies.

Bioactive Protein Hydrolysate Obtained from Canned Sardine and Brewing By-products: Impact of Gastrointestinal Digestion and Transepithelial Absorption

A sardine protein hydrolysate (SPH) was prepared by hydrolysis of sarcoplasmic proteins from canned sardine by-product with proteases from brewer’s spent yeast (BSY). The SPH presented in vitro angiotensin converting enzyme-inhibitory (ACE-I) and ferric reducing antioxidant potential (FRAP). However, the challenge before in vivo efficacy studies is to understand the impact of ultrafiltration (UF), simulated gastrointestinal (GI) digestion, and the intestinal cell permeability. Thus, this work was carried out to study the influence of these parameters on SPH bioactivity; two predictive models for human intestinal absorption were compared. Results showed that ACE-I and antioxidant activities were improved after UF of SPH through a 10 kDa cut-off membrane; simulated GI increased the FRAP value whereas the ACE-I remained similar. The apparent permeability coefficients of < 10 kDa fraction evaluated using Caco-2 and Caco-2/HT29-MTX cell models were 5.89 × 10−6 cm/s and 10.93 × 10−6 cm/s, respectively. Mass spectrometry revealed that molecules with m/z between 1000 and 5000 were transported across Caco-2/HT29-MTX cell monolayer. Basolateral permeates presented antioxidant activity but no ACE-I activity was detected. These results suggest that SPH prepared by BSY proteases is promising as functional ingredient with enhanced antioxidant activity and justifies further in vivo studies to confirm its pharmacological efficacy.

Microplastics as Vectors of Chromium and Lead during Dynamic Simulation of the Human Gastrointestinal Tract

The human body is exposed to the ingestion of microplastics that are often contaminated with other substances, which can be released into our body. In this work, a dynamic in-vitro simulator of the gastrointestinal tract based on a membrane reactor has been used for the first time to study the release, bioaccessibility, and bioavailability of chromium (Cr) and lead (Pb) from polyethylene and polypropylene microplastics previously contaminated in the laboratory. The results showed that 23.11% of the initial Cr and 23.17% of the initial Pb present in microplastics were able to cross the tubular membrane, simulating the intestinal absorption phase. The pH evolution during the gastric phase and the duodenal phase, the interaction mechanisms with physiological fluids, and the properties of the polymers, such as specific surface, porosity, and/or surface degradation, affected the kinetics of release from the microplastics and the behavior of both heavy metals. Cr was released very early in the gastric phase, but also began simultaneously to precipitate quite fast, while Pb was released slower and in less quantity than Cr, and did not precipitate until the beginning of the duodenal phase. This study shows, for the first time, how useful the dynamic gastrointestinal simulator is to study the behavior of microplastics and some problematic heavy metals along the human gastrointestinal tract, and can serve as a reference for future studies focused on the effects of these substances in the human body.

Survival and Germination of Bacillus clausii UBBC07 Spores in in vitro Human Gastrointestinal Tract Simulation Model and Evaluation of Clausin Production.

Bacillus clausii UBBC07 is a commercial spore probiotic known to reduce diarrhea in children and adults. In the present study, survival and germination of UBBC07 spores were investigated under fed and fasted conditions in Simulator of Human Intestinal Microbial Ecosystem. Besides this, lantibiotic production, purification, and characterization were performed. The agar plate analysis showed that spores were 100% tolerant to fed and fasted gastrointestinal tract (GIT) conditions. Simultaneously, flow cytometry revealed that at the end of small intestinal incubation, 120% (fed) and 133% (fasted) spores were in viable germinating state. The transformation of viable germinating spores into viable vegetative cells was observed at 3 h of incubation under fasted GIT conditions. In antimicrobial evaluation, UBBC07 produced low-molecular-weight (2107.94 Da) class I lantibiotic clausin. The presence of lanB, lanC, and lanD genes confirms the clausin production. Clausin is stable at proteases (pepsin, proteinase K, and trypsin), temperature (up to 100°C), and pH (up to 11). Furthermore, the antimicrobial activity toward Gram-positive bacteria including Clostridium difficile is advantageous. In conclusion, B. clausii UBBC07 spore probiotic is capable of surviving and germinating under in vitro upper GIT conditions. The clausin production justifies strain applicability in diarrhea.

Metabolic aspects of phenolic compounds from Triplaris gardneriana seeds in the management of oxidative stress

Objective: Considering the limited number of studies that analyze the behavior of plant preparations in human body, this study aimed to characterize the phenolic compounds from Triplaris gardneriana extract (EETg) in terms of antioxidant and metabolic aspects, integrating in vitro, in silico and in vivo strategies.Methods: EETg was analyzed in relation to polyphenols release from the plant matrix under in vitro digestion, as well as the pharmacokinetic prediction of their major compounds by in silico simulation and understanding of its in vivo antioxidant effect in an alternative animal model.Results: About 35.22% of polyphenols from EETg proved to be accessible after enzymatic hydrolysis. A kinetics study showed that 40% of the total content of these phytochemicals was released from the extract accompanied by increased antioxidant capacity after 180 min of gastrointestinal simulation. A computational approach revealed that 7 out of 9 major phenolic compounds of EETg showed good pharmacokinetic parameters such as intestinal absorption and bioavailability score. In addition, the extract showed a protective effect on copper-induced oxidative stress in Drosophila melanogaster, evidenced by the restoration of basal levels of thiol and malondialdehyde contents. These biochemical observations were supported by the examination of histological features of D. melanogaster brain.Conclusion: It was demonstrated that the oral administration of EETg would provide phenolic compounds partially absorbable by the human gut and capable of providing health benefits associated with the inhibition of oxidative stress. Additionally, the results highlight the need to implement new approaches for the rational development of plant-based medicines.

Application of the Gastrointestinal Simulator (GIS) coupled with in silico modeling to measure the impact of Coca-Cola® on the luminal and systemic behavior of loratadine (BCS class 2b)

Application of the Gastrointestinal Simulator (GIS) coupled with in silico modeling to measure the impact of Coca-Cola® on the luminal and systemic behavior of loratadine (BCS class 2b)

Applying Differential Neural Networks to Characterize Microbial Interactions in an Ex Vivo Gastrointestinal Gut Simulator

The structure of mixed microbial cultures—such as the human gut microbiota—is influenced by a complex interplay of interactions among its community members. The objective of this study was to propose a strategy to characterize microbial interactions between particular members of the community occurring in a simulator of the human gastrointestinal tract used as the experimental system. Four runs were carried out separately in the simulator: two of them were fed with a normal diet (control system), and two more had the same diet supplemented with agave fructans (fructan-supplemented system). The growth kinetics of Lactobacillus spp., Bifidobacterium spp., Salmonella spp., and Clostridium spp. were assessed in the different colon sections of the simulator for a nine-day period. The time series of microbial concentrations were used to estimate specific growth rates and pair-wise interaction coefficients as considered by the generalized Lotka-Volterra (gLV) model. A differential neural network (DNN) composed of a time-adaptive set of differential equations was applied for the nonparametric identification of the mixed microbial culture, and an optimization technique was used to determine the interaction parameters, considering the DNN identification results and the structure of the gLV model. The assessment of the fructan-supplemented system showed that microbial interactions changed significantly after prebiotics administration, demonstrating their modulating effect on microbial interactions. The strategy proposed here was applied satisfactorily to gain quantitative and qualitative knowledge of a broad spectrum of microbial interactions in the gut community, as described by the gLV model. In the future, it may be utilized to study microbial interactions within mixed cultures using other experimental approaches and other mathematical models (e.g., metabolic models), which will yield crucial information for optimizing mixed microbial cultures to perform certain processes—such as environmental bioremediation or modulation of gut microbiota—and to predict their dynamics.