Inflammatory bowel disease (IBD) is defined as a chronic intestinal inflammation that results from host-microbial interactions in a genetically susceptible individual. IBDs are a group of autoimmune diseases that are characterized by inflammation of both the small and large intestine, in which elements of the digestive system are attacked by the body’s own immune system. This inflammatory condition encompasses two major forms, known as Crohn’s disease and ulcerative colitis. Patients affected by these diseases experience abdominal symptoms, including diarrhea, abdominal pain, bloody stools, and vomiting. Moreover, defects in intestinal epithelial barrier function have been observed in a number of patients affected by IBD. In this review, we first describe the types and symptoms of IBD and investigate the role that the epithelial barrier plays in the pathophysiology of IBD as well as the major cytokines involved. We then discuss steps used to diagnose this disease and the treatment options available, and finally provide an overview of the recent research that aims to develop new therapies for such chronic disorders.

Bile acids have received considerable interest in the drug delivery research due to their peculiar physicochemical properties and biocompatibility. The main advantage of bile acids as drug absorption enhancers is their ability to act as both drug solubilizing and permeation-modifying agents. Therefore, bile acids may improve bioavailability of drugs whose absorption-limiting factors include either poor aqueous solubility or low membrane permeability. Besides, bile acids may withstand the gastrointestinal impediments and aid in the transporter-mediated absorption of physically complexed or chemically conjugated drug molecules. These biomolecules may increase the drug bioavailability also at submicellar levels by increasing the solubility and dissolution rate of non-polar drugs or through the partition into the membrane and increase of membrane fluidity and permeability. Most bile acid-induced effects are mediated by the nuclear receptors that activate transcriptional networks, which then affect the expression of a number of target genes, including those for membrane transport proteins, affecting the bioavailability of a number of drugs. Besides micellar solubilization, there are many other types of interactions between bile acids and drug molecules, which can influence the drug transport across the biological membranes. Most common drug-bile salt interaction is ion-pairing and the formed complexes may have either higher or lower polarity compared to the drug molecule itself. Furthermore, the hydroxyl and carboxyl groups of bile acids can be utilized for the covalent conjugation of drugs, which changes their physicochemical and pharmacokinetic properties. Bile acids can be utilized in the formulation of conventional dosage forms, but also of novel micellar, vesicular and polymer-based therapeutic systems. The availability of bile acids, along with their simple derivatization procedures, turn them into attractive building blocks for the design of novel pharmaceutical formulations and systems for the delivery of drugs, biomolecules and vaccines. Although toxic properties of hydrophobic bile acids have been described, their side effects are mostly produced when present in supraphysiological concentrations. Besides, minor structural modifications of natural bile acids may lead to the creation of bile acid derivatives with the reduced toxicity and preserved absorption-enhancing activity.

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Diabetic insulin resistance and pro-diabetic diet are reported to increase dementia risk through unknown mechanisms. Emerging evidence suggests that the integrity of blood-brain barrier (BBB) is central to the onset and progression of neurodegeneration and cognitive impairment. Therefore, the current study investigated the effect of pro-diabetic diets on cognitive dysfunction in association to BBB integrity and its putative mechanisms. In C57BL/6J mice chronically ingested with a diet enriched in fat and fructose (HFF), Morris Water Maze (MWM) test indicated no significant cognitive decline after 4 weeks of HFF feeding compared to low-fat (LF) fed control. However, at this stage, BBB dysfunction accompanied by heightened neuroinflammation in cortex and hippocampal regions was already evident. After 24 weeks, HFF fed mice showed significantly deteriorated cognitive function concomitant with substantial neurodegeneration, which both showed significant associations with increased BBB permeability. In addition, the data indicated that the loss of BBB tight junctions was significantly associated with heightened inflammation and leukocyte infiltration. The data collectively suggest that in mice maintained on pro-diabetic diet, the dysfunctional BBB associated to inflammation and leukocyte recruitment precedes the neurodegeneration and cognitive decline, possibly indicating causal association.

This study utilized the Seahorse Analyzer to examine the effect of the bile acid ursodeoxycholic acid (UDCA), on the morphology, swelling, stability, and size of novel microencapsulated β-cells, in real-time. UDCA was conjugated with fluorescent compounds, and its partitioning within the microcapsules was examined using confocal microscopy. UDCA produced microcapsules with good morphology, better mechanical strength (p < 0.01), and reduced swelling properties (p < 0.01), but lower cell viability (p < 0.05) and cell count per microcapsule (p < 0.01). UDCA reduced the cells' biochemical activities, mitochondrial respiration, and energy production, post-microencapsulation. This is the first time biological functions of microencapsulated β-cells have been analyzed in real-time.

UDCA increased β-cell viability in the microcapsules without affecting the microcapsules' size, morphology, or stability. It also increased the microcapsules' resistance to swelling and optimized their mechanical strength. Our findings suggest potential benefits of the bile acid UDCA in β-cell microencapsulation.

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The aim of this study was to investigate the influence of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats treated with probiotics. Male Wistar rats (2-3 months, 350 +/- 50 g) were randomly allocated into four groups (n = 32); Groups 1 and 2 were healthy controls and Groups 3 and 4 were diabetic rats (alloxan 30 mg/kg was administered i.v.), which were administered probiotics for three days after the rats became diabetics. The rats were sacrificed and tissues were mounted on Ussing chambers. Then, gliclazide (200 microg/ml) was added to all the groups, while MKC (50 microg/ml) was given to Groups 2 and 4, for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. In the tissues of healthy rats treated with probiotics, MKC stimulated the net absorption of gliclazide by stimulating the absorptive and reducing the secretory unidirectional fluxes, while in tissues from diabetic rats treated with probiotics, MKC had no effect. In healthy rats treated with probiotics, the degradation of MKC by bacterial polypeptides produced divalent bile salts that inhibited Mrp2, which resulted in reducing secretion and stimulating the absorption of gliclazide. In contrast, in diabetic rats treated with probiotics, MKC had no effect possibly due to a difference in the metabolic profile and resulting in no net flux.