Evaluation on Intestinal Permeability of Phlorotannins Using Caco-2 Cell Monolayers

Among the phlorotannins of seaweed polyphenols, eckols which have a dibenzodioxin linkage are known to have various physiological functions. The purpose of this study was to investigate the intestinal epithelial absorption of eckols using Caco-2 cell monolayers of the small intestinal membrane model. Each compound permeated from the apical (AP) side to the basolateral (BL) side in the monolayers was identified and quantitated by liquid chromatography-mass spectrometry with electrospray ionization. In the transport assays using five types of eckols (eckol, fucofuroeckol A, phlorofucofuroeckol A, dieckol, and 8,8'-bieckol), only the monomeric eckol showed limited transepithelial absorption with relatively small apparent permeability values (0.30 ± 0.04 × 10−8 cm/s). Analyzing the Hanks’ balanced salt solution in the receiver on the BL side showed that phloroglucinol was detected in all experimental sections using eckols, and it's concentration increased with time over the course of the incubation. The other molecules corresponding to the unconjugated and conjugated metabolites of eckols were not detected in the AP and BL sides through the assays. These results suggest that eckols, including monomeric eckol, may be decomposed into phloroglucinol in the intestinal epithelium and the resulting phloroglucinol permeates to the BL side.

Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain

Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut-brain axis—a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.

Using Porcine Jejunum Ex Vivo to Study Absorption and Biotransformation of Natural Products in Plant Extracts: Pueraria lobata as a Case Study

Herbal preparations (HPs) used in folk medicine are complex mixtures of natural products (NPs). Their efficacy in vivo after ingestion depends on the uptake of the active ingredient, and, in some cases, their metabolites, in the gastrointestinal tract. Thus, correlating bioactivities measured in vitro and efficacy in vivo is a challenge. An extract of Pueraria lobata rich in different types of isoflavones was used to evaluate the capacity of viable porcine small intestine ex vivo to elucidate the absorption of HP constituents, and, in some cases, their metabolites. The identification and transport of permeants across the jejunum was monitored by liquid chromatography-mass spectrometry (LC-MS), combining targeted and untargeted metabolite profiling approaches. It was observed that the C-glycoside isoflavones were stable and crossed the intestinal membrane, while various O-glycoside isoflavones were metabolized into their corresponding aglycones, which were then absorbed. These results are consistent with human data, highlighting the potential of using this approach. A thorough investigation of the impact of absorption and biotransformation was obtained without in vivo studies. The combination of qualitative untargeted and quantitative targeted LC-MS methods effectively monitored a large number of NPs and their metabolites, which is essential for research on HPs.

A Systemic Review on the Self Micro Emulsifying Drug Delivery System

Comfort direction and painless method made oral route the most favored. Mainstream of recent active constituents have less oral bioavailability because of dissolution rate limited absorption. While many inventive methods like complexation, cocrystals exist, solid dispersions, pH modification and, lipid-based delivery systems conclusively improved appliance with the seeming rise in drug absorption. Among lipid-based formulations, self-micro emulsifying formulations (SMEDDS) (droplet size < 100 nm) are evident to enhance permeation across intestinal membrane, protection of drug against gastric effect, unit dosage is possible, increased bioavailability of drug, reduces the dose of drug etc. Numerous components are used to formulate these dosage forms like Oil, surfactants, Co-surfactant and lipids mixture contribute to the enhancement in oral bioavailability through promoting the lymphatic passage; thus, hepatic first pass metabolism can be overcoming. The present review highlights comprehensive information on the formulation design, probable mechanisms and characterization of SMEDDS

The Immune System through the Lens of Alcohol Intake and Gut Microbiota

The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted mucosal immunity. This damage to the permeability of the intestinal membrane allows bacteria and their components to enter the blood tissue, reaching other organs such as the liver or the brain. Although chronic heavy drinking has harmful effects on the immune system cells at the systemic level, this review focuses on the effect produced on gut, brain and liver, because of their significance in the link between alcohol consumption, gut microbiota and the immune system.

ASSESSMENT OF PERMEABILITY BEHAVIOR OF BERBERINE CHLORIDE ACROSS GOAT INTESTINAL MEMBRANE IN PRESENCE OF NATURAL BIOPOTENTIATOR CURCUMIN

The present study investigates the influence of co-administration of different concentrations (2, 6, and 10 mg) of curcumin on goat intestinal permeability of berberine chloride (BBC) using Franz diffusion cell. Data obtained in triplicate from permeability studies were used to calculate percentage cumulative drug release (% CDR), apparent permeability (Papp), flux (J) and enhancement ratio (ER). Co-administration of 6 mg concentration of curcumin with BBC was found to be optimum to enhance the permeability of BBC up to 23.92 ± 0.78 % CDR, over control (8.49 ± 1.45 % CDR). At the optimized concentration of curcumin, permeability characteristics were improved significantly compared to control. The present study reveals the beneficial effect of co-administration of curcumin (6 mg) to promote membrane permeability of BBC which would be expected to improve its bioavailability, thereby therapeutic efficacy. The effect could be attributed to curcumin-mediated inhibition of intestinal efflux pump P-gp, acting as an absorption barrier for BBC.

The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls

Background: IgA nephropathy (IgAN) has been associated with gut dysbiosis, intestinal membrane disruption and translocation of bacteria into blood. Our study aimed to understand the association of gut and blood microbiomes in IgAN patients in relation to healthy controls. Methods: We conducted a case control study with 20 progressive IgAN patients matched with 20 healthy controls, analyzing bacterial DNA quantitatively in blood by 16S PCR and qualitatively in blood and stool by 16S metagenomic sequencing. Between group comparisons as well as comparisons between the blood and gut microbiomes were conducted. Results: Higher median 16S bacterial DNA in blood was found in the IgAN group compared to the healthy controls group (7410 vs 6030 16SrDNA copies/uL blood, p = 0.04). Alpha and beta diversity in both blood and stool was largely similar between the IgAN and healthy groups.. Higher proportions of class Coriobacteriia, and species of genera legionella, Enhydrobacter and parabacteroides in blood; and species of genera Bacteroides, Escherichia-Shigella and some Ruminococcus in stool were observed in IgAN patients in comparison with healthy controls. Taxa distribution were markedly different between the blood and stool samples of each subject in both IgAN and healthy groups without any significant correlation between corresponding gut and blood phyla. Conclusions: Important bacterial taxonomic differences quantitatively in blood and qualitatively in both blood and stool samples detected between IgAN and healthy groups warrant further investigation into their roles in the pathogenesis of IgAN. While gut bacterial translocation into blood may be one of the potential sources of the blood microbiome, marked taxonomic differences between gut and blood samples in each subject in both groups confirms that the blood microbiome does not directly reflect the gut microbiome. Further research is needed into other possible sites of origin and internal regulation of the blood microbiome.

The virtual physiological human gets nerves! How to account for the action of the nervous system in multiphysics simulations of human organs

This article shows how to couple multiphysics and artificial neural networks to design computer models of human organs that autonomously adapt their behaviour to environmental stimuli. The model simulates motility in the intestine and adjusts its contraction patterns to the physical properties of the luminal content. Multiphysics reproduces the solid mechanics of the intestinal membrane and the fluid mechanics of the luminal content; the artificial neural network replicates the activity of the enteric nervous system. Previous studies recommended training the network with reinforcement learning. Here, we show that reinforcement learning alone is not enough; the input–output structure of the network should also mimic the basic circuit of the enteric nervous system. Simulations are validated against in vivo measurements of high-amplitude propagating contractions in the human intestine. When the network has the same input–output structure of the nervous system, the model performs well even when faced with conditions outside its training range. The model is trained to optimize transport, but it also keeps stress in the membrane low, which is exactly what occurs in the real intestine. Moreover, the model responds to atypical variations of its functioning with ‘symptoms’ that reflect those arising in diseases. If the healthy intestine model is made artificially ill by adding digital inflammation, motility patterns are disrupted in a way consistent with inflammatory pathologies such as inflammatory bowel disease.

Cannabinoid Receptors Overexpression in a Rat Model of Irritable Bowel Syndrome (IBS) after Treatment with a Ketogenic Diet

The administration of a ketogenic diet (KD) has been considered therapeutic in subjects with irritable bowel syndrome (IBS). This study aimed to investigate the molecular mechanisms by which a low-carbohydrate diet, such as KD, can improve gastrointestinal symptoms and functions in an animal model of IBS by evaluating possible changes in intestinal tissue expression of endocannabinoid receptors. In rats fed a KD, we detected a significant restoration of cell damage to the intestinal crypt base, a histological feature of IBS condition, and upregulation of CB1 and CB2 receptors. The diet also affected glucose metabolism and intestinal membrane permeability, with an overexpression of the glucose transporter GLUT1 and tight junction proteins in treated rats. The present data suggest that CB receptors represent one of the molecular pathways through which the KD works and support possible cannabinoid-mediated protection at the intestinal level in the IBS rats after dietary treatment.