Gastrointestinal Tract Transit Research Articles

Survival of encapsulated Lactiplantibacillus plantarum probiotics on soft bread throughout gastrointestinal tract transit: Physicochemical characteristics, sensory profile, and functional activity

Bread is one of the most widely consumed foods in the world and is part of the regular diet in many countries. However, white flour bread lacks many valuable nutrients. Inclusion of probiotics can result on bread's quality improvement, but their viability is often affected by food processing and digestion. In this study, maltodextrin and sweet whey were used to encapsulate Lactiplantibacillus plantarum via spray drying. The effect on probiotics survival during heating, storage, and gastrointestinal tract transit, simulated by the INFOGEST in vitro digestion model, was studied. Quality characteristics, sensory analysis, and consumer acceptance were also evaluated. Spray dried bacteria survived in bread during baking at 180 °C and 15 day-storage with a final viability of 7.6 log CFU/g. Encapsulation also ensured the survival of Lactiplantibacillus plantarum during digestion (6.1 log CFU/g), allowing them to be released in the small intestine to exert their health benefits. A difference in bacterial viability between bread crust and crumb was observed, related to oxygen availability and moisture content. A sensory panel did not identify significant differences between bread produced with and without encapsulated bacteria. These results provide new insights regarding addition of encapsulated probiotics for developing functional bakery products favored by consumers.

Interindividual Variation in Gut Nitrergic Neuron Density Is Regulated By GDNF Levels and ETV1

The size and function of the enteric nervous system (ENS) can vary substantially between individuals. Because ENS function is involved in the etiology of a growing number of common human diseases, understanding mechanisms that regulate ENS variation is important. We analyzed RNAseq data from 41 normal adult human colon biopsies and single-cell RNA-seq data from human and mouse developing gut. To establish cause-consequence relationship we used alleles in mice that allow levels change of the candidate effector molecule in the comparable range to human samples. We used siRNA and primary neuronal cultures to define downstream molecular events and characterized gut functional changes in mice where molecular phenotypes paralleled findings in humans. We found that glial cell line-derived neurotrophic factor (GDNF) levels in the human colon vary about 5-fold and correlate strongly with nitrergic marker expression. In mice, we defined that GDNF levels are regulated via its 3' untranslated region (3' UTR) in the gastrointestinal tract and observed similar correlation between GDNF levels and nitrergic lineage development. We identified miR-9 and miR-133 as evolutionarily conserved candidates for negative regulation of GDNF expression in the gastrointestinal tract. Functionally, an increase in inhibitory nitrergic innervation results in an increase in gastrointestinal tract transit time, stool size, and water content accompanied with modestly reduced epithelial barrier function. Mechanistically, we found that GDNF levels regulate nitrergic lineage development via induction of transcription factor ETV1, corroborated by single-cell gene expression data in human and mouse developing enteric neurons. Our results reveal how normal variation in GDNF levels influence ENS size, composition, and gut function, suggesting a mechanism for well-known interindividual variation among those parameters.

Transformation of Nano-Size Titanium Dioxide Particles in the Gastrointestinal Tract and Its Role in the Transfer of Nanoparticles through the Intestinal Barrier.

In this work, the size transformation of the TiO2 nanofraction from pharmaceutical grade E171 powder was studied during its transit through the gastrointestinal tract (GIT). It was shown that pharmaceutical-grade TiO2 powder contained about 0.68% (w/w) of particles smaller than 240 nm in diameter. In the observed GIT transit process the TiO2 nanoparticles were agglomerated up to 150-200 nm in simulated salivary fluid, with gradual agglomerate enlargement up to 300-600 nm and more than 1 micron in simulated gastric fluid. In the intestinal fluid the reverse process occurred, involving a decrease of agglomerates accompanied by the formation of a small fraction with ~50 nm average size. This fraction can be further involved in the histohematic transport process. The acidity degree (pH) and mineral composition of solutions, as well as the transit speed along the gastrointestinal tract, influence the nature of the particle transformation significantly. The rapid passing between the gastrointestinal tract sections creates conditions for a decrease in part of the TiO2 particles, up to 100 nm, and may be associated with the violation of the structural and functional integrity of the intestinal mucus layer.

Understanding the Probiotic Bacterial Responses Against Various Stresses in Food Matrix and Gastrointestinal Tract: A Review.

Probiotic bacteria are known to have ability to tolerate inhospitable conditions experienced during food preparation, food storage, and gastrointestinal tract of consumer. As probiotics are living cells, they are adversely affected by the harsh environment of the carrier matrix as well as low pH, bile salts, oxidative stress, osmotic pressure, and commensal microflora of the host. To overcome the unfavorable environments, many probiotics switch on the cell-mediated protection mechanisms, which helps them to survive, acclimatize and remain operational in the harsh circumstances. In this review, we provide comprehensive understanding on the different stresses experienced by the probiotic when added in carrier food as well as during human gastrointestinal tract transit. Under such situation how these health beneficial bacteria protect themselves by activation of several defense systems and get adapted to the lethal environments.

Conjunction of semi-mechanistic in vitro-in vivo modeling and population pharmacokinetics as a tool for virtual bioequivalence analysis - a case study for a BCS class II drug

Virtual bioequivalence trial (VBE) simulations based on (semi)mechanistic in vitro-in vivo (IVIV) modeling have gained a huge interest in the pharmaceutical industry. Sophisticated commercially available software allows modeling variable drug fates in the gastrointestinal tract (GIT). Surprisingly, the between-subject and inter-occasion variability (IOV) of the distribution volumes and clearances are ignored or simplified, despite substantially contributing to varied plasma drug concentrations. The paper describes a novel approach for IVIV-based VBE by using population pharmacokinetics (popPK). The data from two bioequivalence trials with a poorly soluble BCS class II drug were analyzed retrospectively. In the first trial, the test drug product (biobatch 1) did not meet the bioequivalence criteria, but after a reformulation, the second trial succeeded (biobatch 2). The popPK model was developed in the Monolix software (Lixoft SAS, Simulation Plus) based on the originator’s plasma concentrations. The modified Noyes-Whitney model was fitted to the results of discriminative biorelevant dissolution tests of the two biobatches and seven other reformulations. Then, the IVIV model was constructed by joining the popPK model with fixed drug disposition parameters, the drug dissolution model, and mechanistic approximation of the GIT transit. It was used to simulate the drug concentrations at different IOV levels of the primary pharmacokinetic parameters and perform the VBE. Estimated VBE success rates for both biobatches well reflected the outcomes of the bioequivalence trials. The predicted 90% confidence intervals for the area under the time-concentration curves were comparable with the observed values, and the 10% IOV allowed the closest approximation to the clinical results. Simulations confirmed that a significantly lower maximum drug concentration for biobatch 1 was responsible for the first clinical trial’s failure. In conclusion, the proposed workflow might aid formulation screening in generic drug development.

Do gastrointestinal microbiomes play a role in bats' unique viral hosting capacity?

Bats are reservoirs for zoonotic viruses, which they tolerate without experiencing disease. Research focused on deciphering mechanisms of virus tolerance in bats has rarely considered the influence of their gastrointestinal tract (GIT) microbiome. In mammals, GIT microbiomes influence infections through their effect on host physiology, immunity, nutrition, and behavior. Bat GIT microbiomes more closely resemble the Proteobacteria-dominated GIT microbiomes of birds than those of other mammals. As an adaptation to flight, bats have rapid GIT transit times which may reduce the stability of their microbiome, constrain nutrient uptake, and affect pathogen exposure and evolution of tolerance mechanisms. Experimental and longitudinal studies are needed to understand the function of bats' GIT microbiomes and their role in modulating viral infection dynamics.

Lower ileostomy output among patients with postoperative colorectal cancer after being supplemented with partially hydrolyzed guar gum: Outcome of a pilot study

BackgroundHigh stoma output is a significant complication after bowel surgery that causes dehydration, resulting in acute kidney injury, electrolyte imbalances, unintentional weight loss, and malnutrition. This study evaluates the postoperative ileostomy output among patients with colorectal cancer after being supplemented with partially hydrolyzed guar gum. MethodsThis cross-sectional study collected sociodemographic and clinical characteristics, stoma output, and dietary intake upon discharge, hospitalization, and readmission within 30 d of discharge. ResultsA total of 29 participants were recruited, with 72.4% having moderate malnutrition risk. Patients who received partially hydrolyzed guar gum (PHGG) fiber reported lower stoma output with firmer output consistency than patients who received standard care (SC) (P < 0.05 and P < 0.01). Patients who received PHGG achieved higher energy, protein, and soluble fiber intake than did the SC group (P < 0.01) upon discharge. There was a significant inverse association between soluble fiber (PHGG fiber + dietary soluble fiber) intake and ileostomy output (r, –0.494; P = 0.006). ConclusionsPartially hydrolyzed guar gum fiber acts as an agent to hold water, reduce the speed of gastrointestinal tract transit, increase effluent viscosity, and potentially decrease water losses. Supplementation with PHGG fiber appeared to minimize ileostomy output and improve clinical outcomes among postoperative ileostomy patients. This needs to be evaluated further with a randomized controlled trial to confirm this preliminary finding.

Plumbojarosite Remediation of Soil Affects Lead Speciation and Elemental Interactions in Soil and in Mice Tissues.

Lead (Pb) contamination of soils is of global concern due to the devastating impacts of Pb exposure in children. Because early-life exposure to Pb has long-lasting health effects, reducing exposure in children is a critical public health goal that has intensified research on the conversion of soil Pb to low bioavailability phases. Recently, plumbojarosite (PLJ) conversion of highly available soil Pb was found to decrease Pb relative bioavailability (RBA <10%). However, there is sparse information concerning interactions between Pb and other elements when contaminated soil, pre- and post-remediation, is ingested and moves through the gastrointestinal tract (GIT). Addressing this may inform drivers of effective chemical remediation strategies. Here, we utilize bulk and micro-focused Pb X-ray absorption spectroscopy to probe elemental interactions and Pb speciation in mouse diet, cecum, and feces samples following ingestion of contaminated soils pre- and post-PLJ treatment. RBA of treated soils was less than 1% with PLJ phases transiting the GIT with little absorption. In contrast, Pb associated with organics was predominantly found in the cecum. These results are consistent with transit of insoluble PLJ to feces following ingestion. The expanded understanding of Pb interactions during GIT transit complements our knowledge of elemental interactions with Pb that occur at higher levels of biological organization.

The Role of Nile Tilapia (Oreochromis niloticus) in the Life Cycle of Toxocara spp.

The present study aimed to experimentally assess Nile tilapia as potential paratenic host of Toxocara spp. A total of 15 Nile tilapia (Oreochromis niloticus) were fed with 300 embryonated Toxocara canis eggs by oral gavage, while five others of the control group received distilled water. The fish were individually analyzed at 16, 24, 48, 72, and 240 h after inoculation. Water contamination was assessed, and tissue migration by liver, gastrointestinal tract (GIT), eyes, and central nervous system. A murine model was used as the paratenic host for egg infectivity assessment. Eggs and larvae were found in plastic tank water and fish GIT, ranging from 23 to 86% per fish. Eggs and larvae were recovered from the tank water (76.3%) and fish GIT (23.7%). The counting of eggs and larvae observed was negatively correlated with number of eggs and larvae in the water tank (rho = −0.698, p = 0.003). Shedding of embryonated eggs was first detected at 16 and up to 240 h, with significant egg and larvae yield decrease on water-shedding (p = 0.001) and in the GIT (p = 0.007). Although no T. canis larva was recovered in fish tissues, egg infectivity after fish GIT transit was experimentally confirmed by mice assessment. In conclusion, despite shedding viable embryonated eggs through the gastrointestinal tract, tilapias may not play a role as a suitable paratenic hosts for Toxocara spp., posing low risk of zoonotic transmission by fish meat consumption.

Bioavailable soil Pb minimized by in situ transformation to plumbojarosite

Exposure to lead (Pb) during early life has persistent adverse health effects. During childhood, ingestion of bioavailable Pb in contaminated soils can be a major route of Pb absorption. Remediation to alter physiochemical properties of soil-borne Pb can reduce Pb bioavailability. Our laboratory-based approach for soil Pb remediation uses addition of iron (Fe) sulfate and application of heat to promote formation of plumbojarosite (PLJ), a sparingly soluble Pb-Fe hydroxysulfate mineral. We treated two soils with anthropogenic Pb contamination and samples of clean topsoil spiked with various Pb compounds (i.e., carbonate, chloride, phosphate [P], or sulfate) to convert native Pb species to PLJ and used a mouse assay to assess relative bioavailability (RBA) of Pb in untreated (U) and remediated soils. Bone and blood Pb levels were significantly lower (P < 0.001, Student's t test) in mice that consumed diets amended with remediated soils than with U soils. Estimated RBA for Pb in both remediated natural soils and Pb-mineral spiked soils were reduced by >90% relative to Pb RBA for U soils, which is substantially more effective than other soil amendments, including P. X-ray absorption spectroscopy showed that >90% of all Pb species in remediated soils were converted to PLJ, and ingested PLJ was not chemically transformed during gastrointestinal tract transit. Post treatment neutralization of soil pH did not affect PLJ stability, indicating the feasibility in field conditions. These results suggest that formation of PLJ in contaminated soils can reduce the RBA of Pb and minimize this medium's role as a source of Pb exposure for young children.

Gastric peroral myotomy (G-POEM) in patients with delayed emptying function of the stomach

Introduction. Disorders in the gastric evacuation function are met in patients with gastroesophageal reflux. In most cases, simultaneous laparoscopic pyloroplasty can solve the problem. As an alternative to surgical pyloroplasty to treat gastroparesis, a new technique has been proposed – peroral submucosal pyloromyotomy or gastric peroral endoscopic myotomy (G-POEM). Recently, this endoscopic surgery has been implemented in adults and in newborns with congenital hypertrophic pyloric stenosis to treat gastric paresis. In the present work, the authors describe this technique and short-term results after G-POEM in a child who had previously been operated on for gastroesophageal reflux.Material and methods. Peroral submucosal pyloromyotomy was performed in a girl of 5 y.o. with impaired motor-evacuation function of the stomach after surgical treatment of gastroesophageal reflux disease at the age of two . For 3 years, the child had therapy which included antiemetics and H2-receptor blockers. However, clinical symptoms constantly recurred, and it was decided to make a thorough examination of the patient. At the contrast examination of upper gastrointestinal tract, stomach enlargement and slow transit of the contrast preparation into the duodenum were seen. Fibrogastroduodenoscopy confirmed the normal function of the fundoplication cuff and found a cause of impaired gastric emptying. A contracted gastric outlet as a spasmodic pylorus was found to be an obstacle for normal stomach evacuation function. A narrow hole in the pylorus was found. A 5.4 mm gastroscope could pass through it. The patient had a complete peroral endoscopic submucosal pyloromyotomy. The technique of this surgery consisted in creating a submucosal tunnel at 4 cm before the pylorus and in dissecting the hypertrophied muscle layer by Ramstedt incision using an electrocoagulation knife. After the end of surgery, the incision on the mucous layer was closed with special clamps.Results. Surgical time lasted for 45 minutes. There were no intraoperative complications: bleedings and mucosal perforation . The patient began to eat in 6 hours after the surgery. The transition to full enteral feeding lasted for 24 hours. The child was discharged from the hospital next day in good condition. At the follow-up examination 6 months after surgery, the girl had weight and height typical for her age. There were no signs of dysphagia, abdominal distension, nausea and vomiting any more . There were no post-operative scarring on the child’s abdominal wall.Conclusion. Peroral submucosal pyloromyotomy is technically implementable, safe and effective for treating disorders of stomach evacuation function in children. Further research is needed to find the place of this technique in the treatment of gastric outlet obstruction.

Dietary Lead and Phosphate Interactions Affect Oral Bioavailability of Soil Lead in the Mouse.

Effects of dietary P level on the oral bioavailability of Pb present in soil were examined in a mouse model. Adult female C57BL/6 mice had free access to AIN-93G purified rodent diet amended with Pb as a soluble salt, Pb acetate, or in a soil matrix (NIST SRM 2710a). In these studies, the basal diet contained P at a nutritionally sufficient level (0.3% w/w) and the modified diets contained P at a lower (0.15%) or a higher (1.2%) level. For either dietary Pb source (Pb acetate or NIST SRM 2710a), low dietary P level markedly increased accumulation of Pb in bone, blood, and kidney. Tissue Pb levels in mice fed a high P in diet were not different from mice fed the basal P diet. Dietary P and Pb interacted to affect body weight change and feed efficiency in mice. The relative contribution of different Pb species in diet and feces was also affected by dietary P level. Differences in Pb species between diet and feces indicated that transformation of Pb species can occur during gastrointestinal tract transit. These interactions between Pb and P that alter Pb speciation may be important determinants of the bioavailability of Pb ingested in soil.

Microencapsulation increases survival of the probiotic Lactobacillus plantarum IS-10506, but not Enterococcus faecium IS-27526 in a dynamic, computer-controlled invitro model of the upper gastrointestinal tract.

To test the effect of microencapsulation on the survival of two probiotic strains isolated from Dadih, Indonesian fermented buffalo milk, in a dynamic, computer-controlled invitro model of the upper gastrointestinal (GI) tract (TIM-1), simulating human adults. Free or microencapsulated probiotics, Lactobacillus plantarum IS-10506 or Enterococcus faecium IS-27526, resuspended in milk were studied for survival in the complete TIM-1 system (stomach + small intestine) or in the gastric compartment of TIM-1 only. Hourly samples collected after the ileal-caecal valve or after the pylorus were plated on MRS agar (for Lactobacillus) or S&B agar (for Enterococcus). Survival of the free cells after transit through the complete TIM-1 system was on average for the E. faecium and L. plantarum 15·0 and 18·5% respectively. Survival of the microencapsulated E. faecium and L. plantarum was 15·7 and 84·5% respectively. The free cells were further assessed in only the gastric compartment of TIM-1. E. faecium and L. plantarum showed an average survival of 39 and 32%, respectively, after gastric passage. There is similar sensitivity to gastric acid as well as survival after complete upper GI tract transit of free cells, but microencapsulation only protected L. plantarum. Survival of microencapsulated L. plantarum IS-10506 is increased compared to free cells in a validated invitro model of the upper GI tract. It increases its use as an ingredient of functional foods.

Antidiarrhoeal investigation of Apium leptophyllum (Pers.) by modulation of Na+K+ATPase, nitrous oxide and intestinal transit in rats

BackgroundApium leptophyllum (Pers.) is an annual herb with traditional appreciation for various pharmacological properties; however, the scientific information on this herb is insufficient. The aim of the present investigation was undertaken to evaluate flavonoidal fraction of A. leptophyllum fruit (FFALF) against diarrhoea on albino rats. MethodsThe antidiarrhoeal study was conducted by castor oil induce diarrhoea, prostaglandin E2 (PGE2) induced enteropooling and intestinal transit by charcoal meal test. The rats were divided into five groups (six/group). Group I served as control and received orally 2% acacia suspension; Group II served as standard and received orally loperamide (3 mg/kg) or atropine sulphate (5 mg/kg); Group III, IV and V served as test groups and received the FFALF at doses of 5, 10 and 20 mg/kg orally, respectively. ResultsIn castor oil-induced diarrhoeal model, the FFALF significantly (p < 0.001) reduced the frequency of diarrhoea, defecation and weight of faeces as well as increased the sodium–potassium ATPase (Na+K+ATPase) activity and decreased nitric oxide (NO) content in the small intestine. In prostaglandin induced enteropooling model, it significantly (p < 0.01) and dose dependently slowed the intestinal fluid accumulation by decreasing the masses and volumes of intestinal fluid where as in charcoal meal test, it decreased charcoal meal transit in gastrointestinal tract as compared with control. ConclusionsThe study reveals that the FFALF possess anti-diarrhoeal properties mediated through inhibition of hyper secretion and gastrointestinal motility which support the traditional use of the plant.

Effect of a Ropy Exopolysaccharide-Producing Bifidobacterium animalis subsp. lactis Strain Orally Administered on DSS-Induced Colitis Mice Model.

Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes.

The role of the gastrointestinal tract and microbiota on uremic toxins and chronic kidney disease development.

It is well-established that uremic toxins are positively correlated with the risk of developing chronic kidney disease and cardiovascular disease. In addition, emerging data suggest that gut bacteria exert an influence over both the production of uremic toxins and the development of chronic kidney disease. As such, modifying the gut microbiota may have the potential as a treatment for chronic kidney disease. This is supported by data that suggest that rescuing microbiota dysbiosis may: reduce uremic toxin production; prevent toxins and pathogens from crossing the intestinal barrier; and, reduce gastrointestinal tract transit time allowing nutrients to reach the microbiota in the distal portion of the gastrointestinal tract. Despite emerging literature, the gut-kidney axis has yet to be fully explored. A special focus should be placed on examining clinically translatable strategies that might encourage improvements to the microbiome, thereby potentially reducing the risk of the development of chronic kidney disease. This review aims to present an overview of literature linking changes to the gastrointestinal tract with microbiota dysbiosis and the development and progression of chronic kidney disease.

Comparison of Absorbents and Drugs for Internal Decorporation of Radiocesium: Advances of Polyvinyl Alcohol Hydrogel Microsphere Preparations Containing Magnetite and Prussian Blue

Radiocesium nuclides, used as a gamma ray source in various types of industrial equipments and found in nuclear waste, are strictly controlled to avoid their leakage into the environment. When large amounts of radiocesium are accidentally incorporated into the human body, decorporation therapy should be considered. Although standard decorporation methods have been studied since the 1960s and were established in the 1970s with the drug Radiogardase(®) (a Prussian blue preparation), application of recent advances in pharmacokinetics and ethical standards could improve these methods. Here we designed a modern dosage form of hydrogel containing cesium-absorbents to alleviate intestinal mucosa irritation due to the cesium-binding capacity of the absorbents. The effectiveness of the dosage form on fecal excretion was confirmed by quantitative mouse experiments. The total cesium excretion rate of the crystal form (1.37±0.09) was improved by the hydrogel form (1.52±0.10) at the same dose of Prussian blue, with a longer gastrointestinal tract transit time. Using a mouse model, we compared the effects of several drugs on fecal and urinary excretion of internal cesium, without the use of absorbents. Only phenylephrine hydrochloride significantly enhanced cesium excretion (excretion rate of 1.17±0.08) via the urinary pathway, whereas none of the diuretic drugs tested had this effect. These findings indicate that modifying the dosage form of cesium absorbents is important for the decorporation of internal radiocesium contamination.

The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC

The Biopharmaceutics Classification System (BCS) has found widespread utility in drug discovery, product development and drug product regulatory sciences. The classification scheme captures the two most significant factors influencing oral drug absorption; solubility and intestinal permeability and it has proven to be a very useful and a widely accepted starting point for drug product development and drug product regulation. The mechanistic base of the BCS approach has, no doubt, contributed to its wide spread acceptance and utility. Nevertheless, underneath the simplicity of BCS are many detailed complexities, both in vitro and in vivo which must be evaluated and investigated for any given drug and drug product. In this manuscript we propose a simple extension of the BCS classes to include sub-specification of acid (a), base (b) and neutral (c) for classes II and IV. Sub-classification for Classes I and III (high solubility drugs as currently defined) is generally not needed except perhaps in border line solubility cases. It is well known that the , pKa physical property of a drug (API) has a significant impact on the aqueous solubility dissolution of drug from the drug product both in vitro and in vivo for BCS Class II and IV acids and bases, and is the basis, we propose for a sub-classification extension of the original BCS classification.This BCS sub-classification is particularly important for in vivo predictive dissolution methodology development due to the complex and variable in vivo environment in the gastrointestinal tract, with its changing pH, buffer capacity, luminal volume, surfactant luminal conditions, permeability profile along the gastrointestinal tract and variable transit and fasted and fed states. We believe this sub-classification is a step toward developing a more science-based mechanistic in vivo predictive dissolution (IPD) methodology. Such a dissolution methodology can be used by development scientists to assess the likelihood of a formulation and dosage form functioning as desired in humans, can be optimized along with parallel human pharmacokinetic studies to set a dissolution methodology for Quality by Design (QbD) and in vitro–in vivo correlations (IVIVC) and ultimately can be used as a basis for a dissolution standard that will ensure continued in vivo product performance.

Assessment of potential probiotic properties and multiple bacteriocin encoding-genes of the technological performing strain Enterococcus faecium MMRA

In the present study, Enterococcus faecium MMRA, a safety and technological performing strain, previously isolated from a well-known fermented dairy product of Tunisia, was evaluated for certain properties relevant to probiotic including acid and bile tolerance, gastrointestinal juice resistance and adhesive properties. Acidic pH (2.0–5.0) and bile salt concentrations of 0.3% were used as stress conditions. The adhesive properties were assessed by determination of bacterial hydrophobicity. The strain MMRA showed interesting features such as high tolerance to gastrointestinal tract transit, an extremely high survival rates under stress caused by acidic pHs or bile salts, and a high adhesive potential linked to the elevated percentage of hydrophobicity. Furthermore, the genome of this strain was examined for the occurrence of known enterocin (enterococcal bacteriocins) genes by means of specific PCR assays and this study revealed the genes coding for enterocins A, B, P and X. Although the joint production of these bacteriocins has not been verified, producers of multiple enterocins could have a great technological potential as protective and/or probiotic cultures in the food industry. The results suggested that E. faecium MMRA should be considered as a potential probiotic which meets the criteria to enhance healthy attributes of fermented dairy product besides both of hygienic and sensory aspects.

Protective effect of Dalbergia sissoo Roxb. ex DC. (family: Fabaceae) leaves against experimentally induced diarrhoea and peristalsis in mice

Dalbergia sissoo Roxb. ex DC. (family: Fabaceae; Indian Rosewood), is used in India, especially in rural communities by traditional medicine practitioners to treat diarrhoea. However, scientific evidence does not exist in any literature to substantiate the claim of therapeutic success of the plant species in diarrhoea. To study the protective effect of ethanol extract from D. sissoo Roxb. ex DC. leaves (EDSL) against experimentally induced diarrhoea and peristalsis in mice. Castor oil-induced diarrhoea and magnesium sulphate (MgSO4)-induced diarrhoea tests were used to assess the antidiarrhoeal activity of D. sissoo. Gastrointestinal tract transit of charcoal meal test and barium sulphate milk was used to assess the peristalsis activity of the extract, while the acute toxicity study and determination of total phenolics and total flavonoids were carried out using well-established protocols and methods. The EDSL significantly reduced faecal output in castor oil-induced and MgSO4-induced diarrhoea and also significantly reduced the number of diarrhoeal episodes. D. sissoo significantly delayed the onset of diarrhoea induced by both castor oil and MgSO4 and comparable to loperamide, a standard antidiarrhoeal drug. Both D. sissoo and atropine sulphate significantly reduced the peristalsis activity of charcoal meal and barium sulphate milk in mice. The preliminary phytochemical analysis of EDSL revealed the presence of carbohydrates, phenolics, glycosides, and flavonoids. The median lethal dose of EDSL was greater than 2000 mg/kg (orally (p.o.)). The data obtained indicate that the EDSL has antidiarrhoeal and antiperistalsis activities and thus supports its traditional use. The data also show that the plant material given p.o. may be safe and/or non-toxic in mice.