Assessment Of Intestinal Permeability Research Articles

A customizable and low-cost 3D-printed transwell device coupled with 3D cell culture for permeability assay

The permeability-based assay is commonly used to assess intestinal barrier function, and it relies on using a transwell insert as an essential compartment. The device consists of a semipermeable membrane that is attached at the bottom of the insert and splits the system into the apical and basolateral compartments. However, commercial inserts are standardized with different pore sizes based on the application and offer only a flat plane of two-dimensional cell culture. Herein, we present a simple, low-cost 3D-printed transwell device and a robust method to functionalize the inserts for paper-based 3D cell culture. This 3D-printed device was fabricated from a polylactic acid (PLA) filament, and a paper membrane used to support HT-29 cells for intestinal permeability assessment. A device showed good biocompatibility when culturing HT-29 cells for 48 and 72 h with 97 % and 98 % cell viability, respectively. Together with fluorescence images, cells were attached directly to the microfiber networks of a Matrigel-functionalized paper, indicating that the functionalized paper is biocompatible and bioactive. Furthermore, in a more appropriate culture microenvironment, SEM analyses revealed cellular features differentiating into mucus-secreting cells, evidenced by the formation of microvilli on the cell surface, which was further confirmed by immunofluorescence staining of villin-1. To demonstrate the usability of the 3D-printed transwell device, intestinal permeability was assessed using both chemical and biological stimulation treatments. The permeability results employing FITC-dextran validated the association between a different level of relative fluorescence intensity unit (RFU) and the orange color of live cells by CellTrackerTM. As a result, this 3D-printed transwell device provides a straightforward and cost-effective method for manufacturing a device for customization in many laboratory settings, making it a feasible alternative to marketed transwell devices that do not allow for customization.

Intestinal Inflammation and Permeability in Patients Recovered from SARS-CoV-2 Infection

Introduction: Different works suggest a close link between long COVID gastrointestinal (GI) manifestations and the post-infection disorders of gut-brain interaction (PI-DGBIs). However, the actual mechanisms underlying long-term GI sequelae are still not clear. Our study was aimed to assess both intestinal inflammation and permeability among subjects recovered from SARS-CoV-2 infection and their eventual correlation with long-term GI sequelae. Methods: Eighty-six subjects attending the post-COVID service and recovered from SARS-CoV-2 infection for 6 months were investigated for long COVID manifestations. Those subjects complaining of long-term GI symptoms were further evaluated by Rome IV questionnaire to assess PI-DGBIs. Intestinal inflammation (by fecal calprotectin, FC) and permeability (by serum and fecal levels of zonulin) were evaluated in all subjects. The Hospital Anxiety and Depression Scale (HADS) and the Gastrointestinal Quality of Life Index (GIQLI) questionnaires were further provided to all participants. Results: Thirty-seven subjects (43%) complained of long-term GI symptoms, while 49 subjects (57%) did not. Thirty-three subjects fulfilled Rome IV criteria for PI-DGBIs. FC values resulted higher in those subjects who did not complain GI symptoms (p = 0.03), although remaining quite close to the normal range. No significant differences were shown regarding the assessment of intestinal permeability. By GIQLI, long-term GI sequelae were inversely correlated with quality of life (p = 0.009). Conclusion: Long COVID GI complaints unlikely recognize underlying local inflammatory mechanisms. Since the healthcare, economic, and social burden of post‐COVID DGBIs, a deeper understanding of this emerging condition should be encouraged to improve management of the affected subjects.

The Leaky Gut and Human Diseases: "Can't Fill the Cup if You Don't Plug the Holes First".

The gut barrier is a sophisticated and dynamic system that forms the frontline defense between the external environment and the body's internal milieu and includes various structural and functional components engaged not only in digestion and nutrient absorption but also in immune regulation and overall health maintenance. When one or more components of the intestinal barrier lose their structure and escape their function, this may result in a leaky gut. Mounting evidence emphasizes the crucial role of the gut microbiome in preserving the integrity of the gut barrier and provides insights into the pathophysiological implications of conditions related to leaky gut in humans. Assessment of intestinal permeability has evolved from invasive techniques to noninvasive biomarkers, but challenges remain in achieving consensus about the best testing methods and their accuracy. Research on the modulation of gut permeability is just starting, and although no medical guidelines for the treatment of leaky gut syndrome are available, several treatment strategies are under investigation with promising results. This review discusses the composition of the intestinal barrier, the pathophysiology of the leaky gut and its implications on human health, the measurement of intestinal permeability, and the therapeutic strategies to restore gut barrier integrity.

Isolation of Myenteric and Submucosal Plexus from Mouse Gastrointestinal Tract and Subsequent Co-Culture with Small Intestinal Organoids.

Intestinal homeostasis results from the proper interplay among epithelial cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), smooth muscle cells, the immune system, and the microbiota. The disruption of this balance underpins the onset of gastrointestinal-related diseases. The scarcity of models replicating the intricate interplay between the ENS and the intestinal epithelium highlights the imperative for developing novel methods. We have pioneered a sophisticated tridimensional in vitro technique, coculturing small intestinal organoids with myenteric and submucosal neurons. Notably, we have made significant advances in (1) refining the isolation technique for culturing the myenteric plexus, (2) enhancing the isolation of the submucosal plexus-both yielding mixed cultures of enteric neurons and glial cells from both plexuses, and (3) subsequently co-culturing myenteric and submucosal neurons with small intestinal organoids. This co-culture system establishes neural innervations with intestinal organoids, allowing for the investigation of regulatory interactions in the context of gastrointestinal diseases. Furthermore, we have developed a method for microinjecting the luminal space of small intestinal organoids with fluorescently labeled compounds. This technique possesses broad applicability such as the assessment of intestinal permeability, transcytosis, and immunocytochemical and immunofluorescence applications. This microinjection method could be extended to alternative experimental setups, incorporating bacterial species, or applying treatments to study ENS-small intestinal epithelium interactions. Therefore, this technique serves as a valuable tool for evaluating the intricate interplay between neuronal and intestinal epithelial cells (IECs) and shows great potential for drug screening, gene editing, the development of novel therapies, the modeling of infectious diseases, and significant advances in regenerative medicine. The co-culture establishment process spans twelve days, making it a powerful asset for comprehensive research in this critical field.

Ultrasound-assisted extraction of bioactive compounds from goji berries: Optimization, bioactivity, and intestinal permeability assessment

Lycium barbarum L. berries have a remarkable chemical composition and extensive biological activities, being a valuable component of health and nutraceutical practices. Nevertheless, a deep insight on the intestinal permeation of the pro-healthy bioactive compounds is urgently needed to predict the real effects on human body. This study attempted, for the first time, to optimize the Ultrasound-Assisted Extraction (UAE) of goji berries using a Response Surface Methodology approach and establish the intestinal permeation of the principal pro-healthy compounds. The optimal extraction conditions were a solid:liquid ratio of 8.75 % for 56.21 min, using an intensity of 59.05 W/m2. The optimal extract displayed a remarkable antioxidant capacity, with LC/DAD-ESI-MS analysis unveiled a diverse phytochemical profile, encompassing different compounds (e.g. glu-lycibarbarspermidine F, 2-glu-kukoamine, rutin, 3,5-dicaffeoylquinic acid). The intestinal co-culture model demonstrated that glu-lycibarbarspermidine F (isomer 2) (73.70 %), 3,5-dicaffeoylquinic acid (52.66 %), and isorhamnetin-3-O-rutinoside (49.31 %) traversed the intestinal cell layer, exerting beneficial health-promoting effects.

Development and application of a multi-sugar assay to assess intestinal permeability.

Aim: Bioanalytical assays to measure rhamnose, erythritol, lactulose and sucralose in human urine and plasma were developed to support an indomethacin challenge study for intestinal permeability assessment in healthy participants.Methods: The multi-sugar assays utilized 5-μl sample matrix and a simple chemical derivatization with acetic anhydride, followed by RPLC-MS/MS detection.Results: Rhamnose and erythritol quantification was established between 1.00-1,000μg/ml in urine and 250-250,000ng/ml in plasma. For lactulose and sucralose, dynamic ranges of 0.1-100μg/ml (urine) and 25-25,000ng/ml (plasma) were applied for biological measurements.Conclusion: This work helped overcome some of the common analytical challenges associated with the bioanalysis of mono- and disaccharides and achieved improved limits of quantification.

69 Monoglycerides of Butyric, Caprylic, and Capric Fatty Acids Promote Intestinal Integrity and Host Defenses in Health-Challenged Weanling Pigs

Abstract Frequent incidence of post-weaning enterotoxigenic Escherichia coli (ETEC) diarrhea in the swine industry contributes to high mortality rates and associated economic losses. In this study, the effects of butyric, caprylic, and capric monoglycerides (MG) were investigated as a way to promote intestinal integrity and host defenses in weanling pigs infected with ETEC. A total of 160 pigs of equal sex were allotted to treatment groups based on body weight and sex. Throughout the 17-d study, three treatment groups were maintained: sham-inoculated pigs fed a control diet (NC, n = 40), ETEC-inoculated pigs fed the same control diet (PC, n = 60), and ETEC-inoculated pigs fed the control diet supplemented with the test article included at 3% of the diet (Test, n = 60). Following a 7-d adaptation period, pigs were orally inoculated on each of 3 consecutive days with either 3 mL of a sham-control (saline) or live ETEC culture (3 × 109 CFU/mL). The first day of inoculation was designated as 0 d post-inoculation (DPI), and all study outcomes reference this time-point. Fecal, tissue, and blood samples were collected from 48 individual pigs (NC, n = 12; PC and Test, n = 18) on 5 and 10 DPI for analysis of dry mater (DM), bacterial enumeration, inflammatory markers, and a practical assessment of intestinal permeability. All data were analyzed by ANOVA using the MIXED procedure of SAS. During the peak infection period (5 DPI) the NC group had greater (P < 0.05) fecal DM and lower (P < 0.05) rectal temperatures, total bacteria, total E. coli, and total F18 ETEC. By 9 DPI, the NC and Test groups had numerically decreased lactulose:mannitol ratios in blood plasma compared with the PC group, which indicated possible benefits to intestinal barrier function. Overall, MG supplementation did not appear to influence differences in fecal outcomes that were altered by ETEC infection, but some benefits in intestinal integrity were observed.

Correlation of lactulose-to-mannitol ratios in plasma and urine for intestinal permeability assessment in pigs.

The lactulose-to-mannitol ratio test is a test to assess the disorders associated with gut permeability. The test requires an oral administration of the mixture of lactulose and mannitol and urine collection. The urinary ratio of lactulose to mannitol is an indicator of intestinal permeability. Due to the complexity of urine collection in animal studies, plasma exposure ratios of lactulose to mannitol compared to their urinary concentration ratios were evaluated following an oral administration of the sugar mixture in pigs. 10 pigs were orally dosed with a solution of lactulose and mannitol mixture. Plasma samples were collected at predose, 10 and 30 minutes and 2, 4, and 6 hours postdosing, and cumulated urinary samples were collected at 6 hours for liquid chromatography-mass spectrometry analysis. The ratios of pharmacokinetic parameters of lactulose to mannitol and the plasma sugar ratios at a single time point or the mean values of several time points were compared to their urinary sugar ratios. The results revealed that the lactulose-to-mannitol ratios of AUC0-6h, AUCextrap, and Cmax were correlated to the urinary sugar ratios, and the plasma sugar ratios of a single time point at 2, 4, or 6 hours and the mean values of those time points were also appropriate to replace their urinary ratios in pigs. Following an oral administration of lactulose and mannitol mixture, blood collection, and assay can be an option for assessing intestinal permeability, especially in animal studies.

Fecal and Circulating Biomarkers for the Non-Invasive Assessment of Intestinal Permeability.

The study of intestinal permeability is gaining growing interest due to its relevance in the onset and progression of several gastrointestinal and non-gastrointestinal diseases. Though the involvement of impaired intestinal permeability in the pathophysiology of such diseases is recognized, there is currently a need to identify non-invasive biomarkers or tools that are able to accurately detect alterations in intestinal barrier integrity. On the one hand, promising results have been reported for novel in vivo methods based on paracellular probes, i.e., methods that can directly assess paracellular permeability and, on the other hand, on fecal and circulating biomarkers able to indirectly assess epithelial barrier integrity and functionality. In this review, we aimed to summarize the current knowledge on the intestinal barrier and epithelial transport pathways and to provide an overview of the methods already available or currently under investigation for the measurement of intestinal permeability.

Assessment of Intestinal Permeability and Inflammation Bio-Markers in Patients with Rheumatoid Arthritis.

Increased intestinal permeability and inflammation, both fueled by dysbiosis, appear to contribute to rheumatoid arthritis (RA) pathogenesis. This single-center pilot study aimed to investigate zonulin, a marker of intestinal permeability, and calprotectin, a marker of intestinal inflammation, measured in serum and fecal samples of RA patients using commercially available kits. We also analyzed plasma lipopolysaccharide (LPS) levels, a marker of intestinal permeability and inflammation. Furthermore, univariate, and multivariate regression analyses were carried out to determine whether or not there were associations of zonulin and calprotectin with LPS, BMI, gender, age, RA-specific parameters, fiber intake, and short-chain fatty acids in the gut. Serum zonulin levels were more likely to be abnormal with a longer disease duration and fecal zonulin levels were inversely associated with age. A strong association between fecal and serum calprotectin and between fecal calprotectin and LPS were found in males, but not in females, independent of other biomarkers, suggesting that fecal calprotectin may be a more specific biomarker than serum calprotectin is of intestinal inflammation in RA. Since this was a proof-of-principle study without a healthy control group, further research is needed to validate fecal and serum zonulin as valid biomarkers of RA in comparison with other promising biomarkers.

Novelties on non-invasive biomarkers for the assessment of intestinal permeability and gut barrier integrity in patients with inflammatory bowel diseases.

article: Novelties on non-invasive biomarkers for the assessment of intestinal permeability and gut barrier integrity in patients with inflammatory bowel diseases - Minerva Gastroenterology 2023 March;69(1):1-3 - Minerva Medica - Journals

Predicting intestinal effective permeability of different transport mechanisms: Comparing ex vivo porcine and in vitro dialysis models

Intestinal effective permeability ( P eff ) is among the most critical parameters that determine the bioavailability of nutrients. Rats have been widely used to estimate the P eff of bioactive compounds. However, distinct physiological differences between rats and humans hamper accurate prediction of the P eff . Herein we presented an ex vivo porcine intestinal model to predict the P eff of two model nutrients which involve both active transport ( d -glucose) and passive transport (gallic acid). The results were compared with an in vitro dialysis model which has gained increasing interest in simulating intestinal absorption. The results indicated that the ex vivo porcine model maintained the integrity of the villus epithelium and closely predicted the human P eff of the two compounds. The P eff values of d -glucose obtained from the porcine model (2.37 × 10 −4 cm/s) and the dialysis model with 8000 Da dialysis membrane (2.16 × 10 −4 cm/s) were comparable to that obtained from healthy volunteers, and higher than that revealed by the Caco-2 model, rat in situ and ex vivo models. The P eff obtained from the in vitro dialysis model was affected by the molecular weight cut-off (MWCO). Specifically, the human P eff was closely predicted when 8000 MWCO was selected. The P eff values of gallic acid were 1.70 × 10 −4 cm/s for the porcine model, 1.35 × 10 −4 cm/s for the dialysis model with 8000 Da MWCO, and 1.33 × 10 −4 cm/s for the 1000 Da MWCO, respectively. These values were consistent with those reported in the rat in situ and Ussing chamber models, regardless of intestinal resources. Both models exhibited potential for use in intestinal permeability assessment of nutrients and can serve as a screening tool for nutrient bioavailability and absorption. • An ex vivo porcine model and an in vitro dialysis model were developed and compared to estimate the intestinal permeability ( P eff ). • The ex vivo porcine model maintained mucosal integrity and closely predicted the human P eff of d -glucose (via active transport) and gallic acid (via passive transport). • The in vitro dialysis model closely predicted the P eff of gallic acid, but the P eff of d -glucose was dependent on the molecular weight cut-off (MWCO) of the dialysis membrane. • Both models exhibited potential for use in intestinal permeability assessment of nutrients.

Non-invasive assessment of intestinal permeability in healthy volunteers using transcutaneous fluorescence spectroscopy

The permeability of the intestinal barrier is altered in a multitude of gastrointestinal conditions such as Crohn’s and coeliac disease. However, the clinical utility of gut permeability is currently limited due to a lack of reliable diagnostic tests. To address this issue, we report a novel technique for rapid, non-invasive measurement of gut permeability based on transcutaneous (‘through-the-skin’) fluorescence spectroscopy. In this approach, participants drink an oral dose of a fluorescent dye (fluorescein) and a fibre-optic fluorescence spectrometer is attached to the finger to detect permeation of the dye from the gut into the blood stream in a non-invasive manner. To validate this technique, clinical trial measurements were performed in 11 healthy participants. First, after 6 h of fasting, participants ingested 500 mg of fluorescein dissolved in 100 ml of water and fluorescence measurements were recorded at the fingertip over the following 3 h. All participants were invited back for a repeat study, this time ingesting the same solution but with 60 g of sugar added (known to transiently increase intestinal permeability). Results from the two study datasets (without and with sugar respectively) were analysed and compared using a number of analysis procedures. This included both manual and automated calculation of a series of parameters designed for assessment of gut permeability. Calculated values were compared using Student’s T-tests, which demonstrated significant differences between the two datasets. Thus, transcutaneous fluorescence spectroscopy shows promise in non-invasively discriminating between two differing states of gut permeability, demonstrating potential for future clinical use.

Zonulin and I-FABP are markers of enterocyte damage in celiac disease

To evaluate the level of serum I-FABP (Fatty-Acid-Binding Protein a protein that binds fatty acids) and fecal zonulin as markers of the permeability of the mucous membrane of the small intestine in celiac patients. A total of 151 celiac patients (25 men and 126 women) were examined. The median age was 42 years. Group I included 58 patients with newly diagnosed celiac disease; in group 2 38 patients, knowingly or unknowingly violating the gluten-free diet; group 3 consisted of 55 patients strictly observing gluten-free diet. The control group consisted of 20 healthy volunteers: 4 men and 16 women. All patients underwent esophagogastroduodenoscopy by biopsy of the mucous membrane of the small intestine and assessment of duodenobioptates according to Marsh. In the blood serum, the level of antibodies to tissue transglutaminase IgA and IgG was determined by the enzyme-linked immunosorbent assay using kits manufactured by Orgentec Diagnostics GmbH (Germany), the concentration of I-FABP in blood serum was determined using Hycult Biotech kits (Netherlands). The content of zonulin in feces was investigated by enzyme-linked immunosorbent assay using kits from Immundiagnostik AG (Germany). Statistical analysis was performed using the Statistica 13.3 software (StatSoft Inc., USA). There was a significant increase in the level of antibodies to tissue transglutaminase IgA [120.0 (41.1200)] IU/ml and IgG [31.4 (5.578.9)] IU/ml in patients of group 1 compared with group 2 [IgA 9.1 (2.987.6)] and IgG [3.8 (2.219.7)] IU/ml and group 3 [IgA 1.6 (1.03.2)] and IgG [2.2 (1.152.53)] (p0.01). The level of I-FABP in blood serum in patients of group 1 averaged 2045 pg/ml, in patients in group 2 1406 pg/ml, in patients in group 3 1000 pg/ml. All patients showed a significant increase in the mean I-FABP values compared to controls (1, 2 and control p0.01, 3 and control p=0.016). In patients with Marsh grade III AC atrophy, the I-FABP level depended on the degree of damage to the mucosa and significantly differed from the control: March IIIA (median: 1310 pg/ml, interquartile range: 12121461 pg/ml), March IIIB (median: 2090 pg/ml, interquartile range: 18122322 pg/ml) as well as Marsh IIIC (median: 2058 pg/ml, interquartile range 18582678 pg/ml). The concentration of zonulin in feces in patients of group 1 averaged 111.6 pg/mg, in patients of group 2 90.5 pg/mg. In patients of group 3 50 IU/ml. The concentration of zonulin in feces increased as the degree of mucosa atrophy increased (r=0.585, p0.01). However, despite the fact that both of these markers may indicate impaired permeability, each of them indicates damage to a certain level of the intestinal barrier, which is not always associated with the degree of mucosa atrophy. Determination of serum I-FABP and fecal zonulin levels in celiac patients allows for the assessment of intestinal permeability and can serve as non-invasive markers for monitoring ongoing structural changes in the mucosa without the need for endoscopy.

A Narrative Review about Autism Spectrum Disorders and Exclusion of Gluten and Casein from the Diet.

Objective: Autism spectrum disorders (ASDs) appear in the early stages of neurodevelopment, and they remain constant throughout life. Currently, due to limitations in ASDs treatment, alternative approaches, such as nutritional interventions, have frequently been implemented. The aim of this narrative review is to gather the most relevant and updated studies about dietary interventions related to ASDs etiopathogenesis. Results: Our literature search focused on the gluten- and casein-free (GFCF) diet. The literature found shows the inexistence of enough scientific evidence to support a general recommendation of dietary intervention in children with ASD. Protocols and procedures for assessing risk and safety are also needed. Future lines: Prospective and controlled research studies with larger sample sizes and longer follow-up times are scarce and needed. In addition, studies considering an assessment of intestinal permeability, bacterial population, enzymatic, and inflammatory gastrointestinal activity are interesting to identify possible responders. Besides brain imaging techniques, genetic tests can also contribute as markers to evaluate the comorbidity of gastrointestinal symptoms.

Poly (Lactic-Co-Glycolic) Acid-Poly (Vinyl Pyrrolidone) Hybrid Nanoparticles to Improve the Efficiency of Oral Delivery of β-Carotene.

The aim of this study was to develop a nanoparticle formulation made of poly (vinyl pyrrolidone) (PVP) and poly (lactic-co-glycolic) acid (PLGA) for the oral delivery of β-carotene (BC). The hybrid nanoparticles were prepared by the interfacial deposition method, and the physicochemical properties of this formulation were characterized in terms of its morphology, particle size, size distribution, encapsulation efficiency, dissolution, intestinal permeability, and in vivo pharmacokinetics. Our results demonstrated that BC-loaded nanoformulation and PLGA nanoparticles (PNP) significantly enhanced a release 6.1 times higher than BC suspension. The fortification of PVP into PLGA nanoparticles, named PLGA–PVP hybrid nanoparticles (PPNP), significantly reduced the particle size, as well as led to an increase 1.9 times higher in the in vitro release of BC, compared with PNP. For the ex vivo intestinal permeability assessment, PNP and PPNP–K15 significantly enhanced the intestinal permeability by 2.7 and 6.5 times at the jejunum, and 2.3 and 4.5 times at the ileum, when compared with unformulated BC. According to the pharmacokinetic study, the optimized hybrid formulation significantly increased the peak plasma concentration (Cmax) and the area under the curve (AUC0-t), and the oral relative bioavailability showed a five-fold enhancement compared with that of the BC suspension. Our results indicate that the hybrid nanoparticulate delivery system is an efficient strategy for the oral delivery of BC.

Berberine represses Wnt/β-catenin pathway activation via modulating the microRNA-103a-3p/Bromodomain-containing protein 4 axis, thereby refraining pyroptosis and reducing the intestinal mucosal barrier defect induced via colitis

ABSTRACT Intestinal barrier dysfunction is inflammatory bowel disease’s hallmark. Berberine (BBR) has manifested its anti-inflammatory properties in colitis. For exploring the molecular mechanism of BBR’s impacts on colitis, application of a dextran sodium sulfate-induced mouse colitis in vivo model was with recording the body weight, stool consistency, stool occult blood and general physical symptoms of all groups of mice every day. Behind assessment of intestinal permeability, detection of colon damage’s degree and apoptosis, and inflammatory factors for assessment of pyroptosis was conducted. Application of interleukin-6-stimulated Caco-2 cells was for construction of an in vitro model. Then detection of cell advancement with inflammation and measurement of the barrier’s integrity were put into effect. Verification of microRNA (miR)-103a-3p and Bromodomain-containing protein 4 (BRD4)’s targeting link was conducted. Experiments have clarified BBR, elevated miR-103a-3p or repressive BRD4 was available to alleviate colitis-stimulated pyroptosis and intestinal mucosal barrier defects. BBR elevated miR-103a-3p to target BRD4; Refraining miR-103a-3p or enhancive BRD4 turned around BBR’s therapeutic action on colitis injury. BBR depressed Wnt/β-catenin pathway activation via controlling the miR-103a-3p/BRD4 axis. All in all, BBR represses Wnt/β-catenin pathway activation via modulating the miR-103a-3p/BRD4 axis, thereby mitigating colitis-stimulated pyroptosis and the intestinal mucosal barrier defect. The research suggests BBR is supposed to take on potential in colitis cure.

Methods for induction and assessment of intestinal permeability in rodent models of radiation injury.

Ionizing radiation (IR) is a significant contributor to the contemporary market of energy production and an important diagnostic and treatment modality. Besides having numerous useful applications, it is also a ubiquitous environmental stressor and a potent genotoxic and epigenotoxic agent, capable of causing substantial damage to organs and tissues of living organisms. The gastrointestinal (GI) tract is highly sensitive to IR. This problem is further compounded by the fact that there is no FDA-approved medication to mitigate acute radiation-induced GI syndrome. Therefore, establishing the animal model for studying IR-induced GI-injury is crucially important to understand the harmful consequences of intestinal radiation damage. Here, we discuss two different animal models of IR-induced acute gastrointestinal syndrome and two separate methods for measuring the magnitude of intestinal radiation damage.

Biomarkers for assessment of intestinal permeability in clinical practice.

Intestinal permeability is an important diagnostic marker, yet its determination by established tests, which measure the urinary excretion of orally administered tracer molecules, is time consuming and can only be performed prospectively. Here, we aim to validate proposed surrogate biomarkers, which allow measuring intestinal permeability more easily. In this cross-sectional study, we included two independent cohorts comprising nonobese (Healthy cohort, n = 51) and individuals with obesity (Obesity cohort, n = 27). The lactulose/mannitol (lac/man) ratio was determined in all individuals as an established marker of intestinal permeability. Furthermore, we measured six potential surrogate biomarkers, being albumin, calprotectin, and zonulin, measured in feces, as well as intestinal fatty acid binding protein (I-FABP), lipopolysaccharide binding protein (LBP) and zonulin, measured in plasma. Correlation analyses and multiple linear regression models were conducted to assess possible associations between the established lac/man ratio and the proposed biomarkers by also evaluating a potential effect of age, body mass index (BMI), and sex. The lac/man ratio correlated with plasma LBP levels in all cohorts consistently and with the amount of fecal zonulin in overweight and obese individuals. Multiple linear regression models showed that the association between the lac/man ratio and plasma LBP was independent of age, BMI, and sex. Fecal zonulin levels were associated with the lac/man ratio as well as BMI, but not age and sex. Our data suggest plasma LBP as a promising biomarker for intestinal permeability in adults and fecal zonulin as a potential biomarker in overweight and obese individuals.NEW & NOTEWORTHY This study shows that biomarkers from blood and fecal samples are associated with the cumbersome established tests of intestinal permeability throughout different cohorts. Therefore, such biomarkers could be used to assess gut barrier function in prospective cohort studies and large-scale clinical trials for which tracer-based tests may not be feasible.

The Effect of Perioperative Administration of Probiotics on Colorectal Cancer Surgery Outcomes.

The perioperative care of colorectal cancer (CRC) patients includes antibiotics. Although antibiotics do provide a certain protection against infections, they do not eliminate them completely, and they do carry risks of microbial resistance and disruption of the microbiome. Probiotics can maintain the microbiome’s balance postoperatively by maintaining intestinal mucosal integrity and reducing bacterial translocation (BT). This review aims to assess the role of probiotics in the perioperative management of CRC patients. The outcomes were categorised into: postoperative infectious and non-infectious complications, BT rate analysis, and intestinal permeability assessment. Fifteen randomised controlled trials (RCTs) were included. There was a trend towards lower rates of postoperative infectious and non-infectious complications with probiotics versus placebo. Probiotics reduced BT, maintained intestinal mucosal permeability, and provided a better balance of beneficial to pathogenic microorganisms. Heterogeneity among RCTs was high. Factors that influence the effect of probiotics include the species used, using a combination vs. single species, the duration of administration, and the location of the bowel resection. Although this review provided evidence for how probiotics possibly operate and reported notable evidence that probiotics can lower rates of infections, heterogeneity was observed. In order to corroborate the findings, future RCTs should keep the aforementioned factors constant.