Intestinal Disease Research Articles

Perspectives on the extracellular matrix in inflammatory bowel disease and bowel decellularization protocols

The extracellular matrix (ECM) is a non-cellular three-dimensional structure present in all tissues that is essential for the intestinal maintenance, function and structure, as well as for providing physical support for tissue integrity and elasticity. ECM enables the regulation of various processes involved in tissue homeostasis, being vital for healing, growth, migration and cell differentiation. Structurally, ECM is composed of water, polysaccharides and proteins, such as collagen fibers and proteoglycans, which are specifically arranged for each tissue. In pathological scenarios, such as inflammatory bowel disease (IBD), the deposition and remodeling of the ECM can be altered in relation to the homeostatic composition. IBD, such as Ulcerative colitis and Crohn’s disease, can be differentiated according to ECM alterations, such as circulating levels of collagen, laminin and vimentin neoepitopes. In this context, ECM presents particularities in both physiological and pathological processes, however, exploring methods of tissue decellularization is emerging as a promising frontier for new therapeutic interventions and clinical protocols, promoting the development of new approaches to intestinal diseases.

Bacterial attachment and junctional transport function in induced apical-out polarized and differentiated canine intestinal organoids

Dogs are increasingly recognized as valuable large animal models for understanding human intestinal diseases, as they naturally develop conditions similar to those in humans, such as Enterohemorrhagic E. coli, Clostridium difficile infection, inflammatory bowel disease, and ulcerative colitis. Given the similarity in gut flora between dogs and humans, canine in vitro intestinal models are ideal for translational research. However, conventional extracellular matrix-embedded organoids present challenges in accessing the lumen, which is critical for gut function. This study aimed to investigate the feasibility of inducing polarity reversal and differentiation in canine apical-out colonic organoids (colonoids), evaluate their barrier integrity, and visualize host-pathogen interactions. Our results demonstrated successful polarity reversal and differentiation induction while maintaining barrier integrity. Polarity reversal allowed for enhanced observation of host-pathogen interactions, facilitating visual assessments and membrane integrity evaluations using both pathogenic and nonpathogenic E. coli. This process led to the downregulation of stem cell marker LGR5 and upregulation of intestinal epithelial cell marker ALPI, indicating differentiation. Further differentiation was observed with the use of a differentiation culture medium, resulting in significant upregulation of ALPI and goblet cell marker MUC2. The findings suggest that apical-out canine colonoids can serve as physiologic and valuable models for studying the pathogenic mechanisms and clinical significance of intestinal diseases in dogs. This model has the potential to advance both canine and human gastrointestinal research, enhancing our understanding of gastrointestinal physiology and pathology and aiding in the development of novel therapeutics.

Amoebae: beyond pathogens- exploring their benefits and future potential

Amoebae, fascinatingly diverse protists, showcase a dual nature that positions them as both friends and foes in our world. These organisms, defined by their distinctive pseudopodia, span a spectrum from harmful to helpful. On the darker side, species like Entamoeba histolytica pose serious health risks, causing intestinal and liver diseases, while the infamous “brain-eating” Naegleria fowleri leads to fatal primary amoebic meningoencephalitis (PAM), with a daunting 97% mortality rate. Other free-living amoebae, including Acanthamoeba castellanii and Balamuthia mandrillaris, also threaten the human central nervous system. Yet, beyond these dangers, amoebae play critical ecological roles. They function as nature’s recyclers, decomposing organic material and nourishing aquatic ecosystems, while also serving as food for various organisms. Moreover, certain amoebae help control plant pathogens and offer insight into human disease, proving valuable as model organisms in biomedical research. This review sheds light on the complex, multifaceted world of amoebae, highlighting their dual role as pathogens and as key contributors to vital ecological processes, as well as their significant impact on research and their promising potential for enhancing human well-being.

Small intestinal bacterial overgrowth and metabolic dysfunction-associated steatotic liver disease

Small intestinal bacterial overgrowth (SIBO), characterized by alterations in both the type and quantity of bacteria in the small intestine, leads to impaired intestinal digestion and absorption that can cause a range of clinical symptoms. Recent studies have identified significant changes in the composition of the small intestinal microbiota and metabolomic profiles of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study systematically reviewed and synthesized the available data to explore the association between SIBO and MASLD. Comprehensive literature searches of the Embase, PubMed, Web of Science, Ovid, and Cochrane databases were conducted. Article quality screening was performed using the Newcastle-Ottawa Quality Assessment Scale. Cross-sectional, cohort, and case–control studies were included. A total of 7,200 articles were initially screened, of which 14 were ultimately included for analysis. Individuals with SIBO in both the MASLD and non-MASLD groups were extracted and a chi-square test was performed to calculate the odds ratio (OR) and 95% confidence interval (CI). The I2 index was used to measure heterogeneity. For heterogeneity >50%, a random effects model was used. There was a clear association between SIBO and MASLD (OR = 3.09; 95% CI 2.09–4.59, I2 = 66%, p < 0.0001). Subgroup analyses by MASLD stage showed that the probability of SIBO positivity increased with MASLD lesion severity. After stratifying by the diagnostic methods for SIBO and MASLD, the meta-analysis results suggest a reduction in inter-group heterogeneity. For the MASLD subgroup diagnosed via liver biopsy, the OR was 4.89. A subgroup analysis of four studies that included intestinal permeability testing revealed an OR of 3.86 (95% CI: 1.80–8.28, I2 = 9%, p = 0.0005). A meta-regression analyses revealed that both race and regional development level significantly influenced the relationship between SIBO and MASLD (p = 0.010, p = 0.047). In conclusion, this meta-analyses provides strong evidence that SIBO may contribute to the development and progression of MASLD. The strongest associations were observed between lactulose breath testing, gut microbiota culture, liver biopsy diagnosis of MASLD, and SIBO detected through intestinal permeability testing. The primary sources of heterogeneity are race and developed regions.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=427040.

Endoscopic Approaches for Managing Small Intestinal Disease.

The endoscopic evaluation and management of small intestinal diseases continue to evolve and expand. The advent of small bowel wireless capsule endoscopy and deep enteroscopy with either a double- or single-balloon enteroscope now allows complete endoscopic visualization of the entire small intestine and enables access for endoscopic interventions such as biopsies or hemostasis for most of the small bowel. New endoscopic techniques are available to treat proximal malignant small bowel obstruction, including intraluminal stents and endoscopic gastrojejunal stents. Emerging technologies also aim to improve weight loss and diabetes management via small bowel endoscopic interventions.

Combined Bulk and Single-Cell Transcriptomic Analysis to Reveal the Potential Influences of Intestinal Inflammatory Disease on Multiple Sclerosis.

Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are both autoimmune disorders caused by dysregulated immune responses. Still, there is a growing awareness of the comorbidity between MS and IBD. However, the shared pathophysiological mechanisms between these two diseases are still lacking. RNA sequencing datasets (GSE126124, GSE9686, GSE36807, GSE21942) were analyzed to identify the shared differential expressed genes (DEGs) for IBD and experimental allergic encephalomyelitis (EAE). Other datasets (GSE17048, GSE75214, and GSE16879) were downloaded for further verification and analysis. Shared pathways and regulatory networks were explored based on these DEGs. The single-cell transcriptome of central nervous system (CNS) immune cells sequenced from EAE brains and the public datasets of IBD (PRJCA003980) were analyzed for the immune characteristics of the shared DEGs. Mass cytometry by time-of-flight (CyTOF) of peripheral blood mononuclear cells (PBMCs) was performed for the systematic immune response in the EAE model. Machine learning algorithms were also used to identify the diagnostic biomarkers of MS. We identified 74 common DEGs from the selected RNA sequencing datasets, and single-cell RNA data of the intestinal tissues of IBD patients showed that 56 of 74 DEGs were highly enriched in IL1B+ macrophages. These 56 DEGs, defined as inflammation-related DEGs (IRGs), were also highly expressed in pro-inflammatory macrophages of EAE mice and MS patients. The abundance of systematic CD14+ monocytes was validated by CyTOF data. These IRGs were highly enriched in immune response, NOD-like receptor signaling pathway, IL-18 signaling pathway, and other related pathways. In addition, 'AddModuleScore_UCell' analysis further validated that these IRGs (such as IL1B, S100A8, and other inflammatory factors) are highly expressed mainly in pro-inflammatory macrophages, which play an essential role in pro-inflammatory activation in IBD and multiple sclerosis, such as IL-17 signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Finally, suppressors of cytokine signaling 3(SOCS3) and formyl peptide receptor 2(FPR2) were identified as potential biomarkers by machine learning. Two genes were highly expressed in pro-inflammatory macrophages of IBD and MS disease compared to control, and other datasets and experiments further revealed that SOCS3 and FPR2 were highly expressed in IBD and EAE samples. These shared IRGs, which encode inflammatory cytokines, exhibit high expression levels in inflammatory macrophages in IBD and may play a significant role in the inflammatory cytokine storm in MS patients. Two potential biomarkers, SOCS3 and FPR2, were screened out with great diagnostic value for MS and IBD.

Lipocalin-2 and intestinal diseases.

Dysfunction of the intestinal barrier is a prevalent phenomenon observed across a spectrum of diseases, encompassing conditions such as mesenteric artery dissection, inflammatory bowel disease, cirrhosis, and sepsis. In these pathological states, the integrity of the intestinal barrier, which normally serves to regulate the selective passage of substances between the gut lumen and the bloodstream, becomes compromised. This compromised barrier function can lead to a range of adverse consequences, including increased permeability to harmful substances, the translocation of bacteria and their products into systemic circulation, and heightened inflammatory responses within the gut and beyond. Understanding the mechanisms underlying intestinal barrier dysfunction in these diverse disease contexts is crucial for the development of targeted therapeutic interventions aimed at restoring barrier integrity and ameliorating disease progression. Lipocalin-2 (LCN2) expression is significantly upregulated during episodes of intestinal inflammation, making it a pivotal indicator for gauging the extent of such inflammatory processes. Notably, however, LCN2 derived from distinct cellular sources, whether intestinal epithelial cells or immune cells, exhibits notably divergent functional characteristics. Furthermore, the multifaceted nature of LCN2 is underscored by its varying roles across different diseases, sometimes even demonstrating contradictory effects.

Temporary Nanoencapsulation of Human Intestinal Organoids Using Silk Ionomers.

Human intestinal organoids (HIOs) are vital for modeling intestinal development, disease, and therapeutic tissue regeneration. However, their susceptibility to stress, immunological attack, and environmental fluctuations limits their utility in research and therapeutic applications. This study evaluated the effectiveness of temporary silk protein-based layer-by-layer (LbL) nanoencapsulation technique to enhance the viability and functions of HIOs against common biomedical stressors, without compromising their native functions. Cell viability and differentiation capacity are assessed, finding that nanoencapsulation significantly improved HIO survival under the various environmental perturbations studied without compromising cellular functionality. Post-stress exposures, the encapsulated HIOs still successfully differentiated into essential intestinal cell types such as enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Moreover, the silk nanocoatings effectively protected against environmental stressors such as ultraviolet (UV) light exposure, protease degradation, antibody binding, and cytokine-induced inflammation. This nanoencapsulation technique shows promise for advancing HIO applications in disease modeling, drug testing, and potential transplantation therapies.

Clostridium butyricum, a future star in sepsis treatment

Sepsis is a systemic inflammatory response syndrome of multiorgan failure caused by dysregulation of the host response to infection and is a major cause of death in critically ill patients. In recent years, with the continuous development of sequencing technology, the intestinal microecology of this disease has been increasingly studied. The gut microbiota plays a host-protective role mainly through the maintenance of normal immune function and the intestinal barrier. Recent evidence suggests that intestinal flora dysbiosis plays a crucial role in sepsis. Clostridium butyricum (C. butyricum), which has been used as a probiotic in poultry feed since its discovery, has been found to play a potential protective role in intestinal infections, inflammatory bowel disease (IBD), colorectal cancer, and other diseases in recent studies. In this review, we continue to focus on the important role and mechanism of C. butyricum as a probiotic in human diseases, especially intestinal diseases. Additionally, we evaluate the research progress of C. butyricum in treatment of sepsis to identify more therapeutic targets for the clinical treatment of sepsis.

Huanglian decoction prevents and treats radiation-induced intestinal injury in lung cancer by regulating endoplasmic reticulum stress.

Radiotherapy is a primary treatment method for lung cancer, and radiation-induced lung injury has been widely studied. However, the lung and intestines are closely related, and patients receiving lung radiotherapy often experience gastrointestinal reactions. Huanglian Decoction has proven effective in treating intestinal diseases, but its role in radiation-induced intestinal injury in lung cancer has not yet been demonstrated. The study investigated the potential protective mechanisms of Huanglian Decoction against radiation-induced intestinal injury in lung cancer. In vivo experiments were conducted to examine the morphological changes. Changes in endoplasmic reticulum stress-related proteins were assessed using electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. In vitro studies involved the overexpression of TRPA1 protein in NCM460 cells via lentiviral vectors. Tumor-bearing mice exhibited severe damage to both lung and colon tissues following radiotherapy, with elevated levels of IL-33, increased expression of ST2L and TRPA1 in colon tissues, higher levels of endoplasmic reticulum stress-related proteins, and the presence of apoptosis and inflammatory responses. Huanglian Decoction reduced radiation-induced intestinal injury by lowering IL-33 levels, which in turn reduced endoplasmic reticulum stress response in colon tissues. In TRPA1-overexpressing NCM460 cells, Huanglian Decoction decreased TRPA1 expression levels and significantly alleviated endoplasmic reticulum stress response. Conclusively, the results indicate that Huanglian Decoction alleviates radiation-induced intestinal endoplasmic reticulum stress by reducing IL-33 levels, subsequently inhibiting the expression of ST2L and TRPA1 in colon tissues. This demonstrates the protective effect of Huanglian Decoction on the intestines during lung cancer radiotherapy, highlighting its promising clinical application in radiation protection.

Delivery of Encapsulated Intelligent Engineered Probiotic for Inflammatory Bowel Disease Therapy.

Engineered bacterial therapy holds enormous potential for treating intestinal diseases, employing synthetic biology techniques to achieve localized drug delivery within intestines. However, effective delivery of engineered bacteria to lesion sites and ensuring sustained colonization remain challenging. Here, a mucus encapsulated microsphere gel (MM) delivery system is developed to encapsulate genetically engineered bacteria capable of detecting and treating enteritis. The MM delivery system features an external mucosal coating composed of hyaluronic acid and epigallocatechin gallate, along with internal microspheres of highly biocompatible polyserine modified alginates encapsulating with the engineered probiotics. The MM delivery system effectively protects engineered bacteria harsh environment in stomach and significantly improves intestinal adhesion of the probiotics, extending colonization up to 24h, and does not affect the entry of biomarker or release of Avcystatin. It exhibits notable diagnostic and therapeutic efficacy in inflammatory bowel disease models, thus facilitating the advancement of live biotherapeutic products toward clinical application.

Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy

The need for basement membrane extract (BME) with undefined constituents, such as Matrigel, for intestinal stem cell (ISC) culture in traditional systems poses a significant barrier that must be overcome for the development of clinical-grade, scalable, ready-to-use ISCs. Here, we propose a functional polymer-based xenogeneic-free dish for the culture of intestinal stem cells (XF-DISC), ensuring substantially prolonged maintenance of ISCs derived from 3-dimensional human intestinal organoids (ISCs3D-hIO). XF-DISC enables remarkable expandability, exhibiting a 24-fold increase in cell numbers within 30 days, with long-term maintenance of ISCs3D-hIO for more than 30 consecutive passages (>210 days). In addition, XF-DISC is fully compatible with a cell banking system. Notably, human pluripotent stem cell-derived ISCs3D-hIO cultured on XF-DISC are successfully transplanted into intestinal injury and inflammation mouse models, leading to engraftment and regeneration of damaged mouse intestinal epithelium. As a reliable and scalable xenogeneic-free ISC3D-hIO culture method, XF-DISC is highly promising for the development of regenerative ISC therapy for human intestinal diseases.

Akkermansia muciniphila: A promising probiotic against inflammation and metabolic disorders.

Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, A. muciniphila regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of A. muciniphila are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live A. muciniphila, but also in pasteurized A. muciniphila, A. muciniphila-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and A. muciniphila, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of A. muciniphila on different diseases and summarize the potential mechanisms of action of A. muciniphila in the treatment of diseases. We provide a comprehensive understanding of A. muciniphila for improving host health and discuss the perspectives of A. muciniphila in the future studies.

Validation of intestinal ultrasound scores in assessing endoscopic activity of colonic and small intestinal Crohn's disease in a southwest Chinese cohort: a retrospective cross-sectional study.

Recently, intestinal ultrasound (IUS) scores such as International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and Simple Ultrasound Score for Crohn's Disease (SUS-CD) have been established to evaluate disease activity in Crohn's disease (CD), but these require further external validation. This study thus aimed to compare recent IUS scores in patients with colonic or small intestinal CD in order to objectively assess their value and appropriate application. This retrospective study consecutively enrolled data of patients with CD from October 2020 to November 2022. The endoscopic and ultrasound images were collected, and the affected segments were rescored according to endoscopic scores [Simple Endoscopic Score for Crohn's Disease (SES-CD), Rutgeerts score for patients who have undergone surgery, and the Lewis score for CD of the small intestine]; IUS scores were also collected, including the IBUS-SAS, Ultrasound Consolidated Score (UCS), SUS-CD, Simple Ultrasound Score (Simple US Score), and Bowel Ultrasound Score (BUSS). Subsequently, the correlation of IUS scores with endoscopic scores and the identification of disease activity was calculated. The Spearman rank correlation coefficient was used to calculate the correlation of parameters, and the Kruskal-Wallis test was used to compare different groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficiency of each score, and corresponding area under the curve (AUC), cutoff values, sensitivity, specificity, and 95% confidence intervals (CIs) were calculated. A total of 203 patients were included in this study. All scores correlated well with endoscopic scores and showed the ability to identify colonic CD activity with high sensitivity and specificity. Among all the scores, IBUS-SAS had the highest value overall and for colonic CD, with sensitivity of 92.7% and a specificity of 91.4% in identifying endoscopic activity and a sensitivity of 95.0% and a specificity of 88.2% in identifying severe endoscopic activity. In small intestinal CD, the UCS showed the highest correlation with endoscopic score, with a relative coefficient of 0.708. The corresponding cutoff values for identifying endoscopic activity and severe activity were also calculated. Consistent with endoscopy, IUS scores are accurate in retrospective activity evaluation of CD, and suitable scores can be chosen according to the given circumstances.

Applications of Text Mining techniques to extract meaningful information from gastroenterology medical reports

Text mining techniques, particularly topic modeling, can be used for the automatic extraction of information from medical reports. The ability to autonomously analyze texts and identify topics within them can provide meaningful clinical insights that support physicians in diagnostic settings and enhance the characterization of intestinal diseases, leading to more efficient and automated systems.This study evaluates the effectiveness of Latent Dirichlet Allocation (LDA) and BERTopic in modeling topics from colonoscopy reports related to Crohn’s Disease, Ulcerative Colitis, and Polyps. We compared these models in terms of their ability to identify clinically relevant topics, their influence on the performance of machine learning classifiers trained on the derived topic features, and their scalability.Our analysis, based on average results across five iterations of train-test splits, showed that BERTopic generally outperformed LDA in clustering metrics, achieving Adjusted Rand Index (ARI), Normalized Mutual Information (NMI), and Purity scores of 0.5637, 0.5953, and 0.8447, respectively, compared to LDA’s scores of 0.5349, 0.5254, and 0.8149. Additionally, classifiers trained on BERTopic-derived features exhibited improved predictive accuracy and F1-scores, with Logistic Regression reaching a mean accuracy of 0.8464 and a mean F1-score of 0.8507, compared to 0.8319 and 0.8351 for LDA-based features. Despite BERTopic’s overall superior performance, LDA demonstrated greater stability and interpretability, making it a viable option in scenarios where computational efficiency is a priority.

An epidemiological investigation of the prevalence of digestive diseases in the older prisoner population in Taiwan

ObjectiveThe prison population has been increasing globally, and prisoner health is an important issue of global health. However, it has not received sufficient attention, especially in developing countries and regions. Among all the prisoners, the health status of older prisoners requires special attention due to their declining health and energy. This study aims to assess the prevalence of digestive diseases among older prisoners in Taiwan.MethodsData on older prisoners from the National Health Insurance Research Database from January 1 to December 31, 2013, were used in this study. Digestive diseases were assessed in 2,215 older prisoners using the International Classification of Diseases, 9th revision Clinical Modification (ICD-9-CM). We identified the most common digestive diseases and explored any sex-specific differences in their prevalence.ResultsThe estimated prevalence of digestive system diseases among the prisoners was 51.56%. Older women prisoners had a higher prevalence (62.68%) compared to men prisoners in general (50.80%). Diseases with a prevalence > 10% include esophageal, gastric, and duodenal diseases; diseases of the oral cavity, salivary glands, and jaws; and other intestinal and peritoneal diseases. Women prisoners showed a significantly higher prevalence of diseases of the oral cavity, salivary glands, jaws, esophagus, stomach, duodenum, non-infectious enteritis, and colitis.ConclusionOur findings indicate that a considerable number of older prisoners in Taiwan experienced digestive diseases, which may be attributable to general deterioration of physical function and poor resistance. Early detection and treatment are crucial for these conditions, and it is important to maintain human rights and justice in prison systems.

Human milk extracellular vesicles modulate inflammation and cell survival in intestinal and immune cells.

Human milk contains extracellular vesicles (EVs) that carry bioactive molecules such as microRNA, to the newborn intestine. The downstream effects of EV cargo on signaling and immune modulation may shield neonates against inflammatory diseases, including necrotizing enterocolitis. Premature infants are especially at risk, while human milk-feeding may offer protection. The effect of gestational-age specific term and preterm EVs from transitional human milk was characterized on human intestinal epithelial cells (HIECs and Caco-2), primary macrophages, and THP-1 monocytes. We hypothesized that term and preterm EVs differentially influence immune-related cytokines and cell death. We found that preterm EVs were enriched in CD14 surface marker, while both term and preterm EVs increased epidermal growth factor secretion. Following inflammatory stimuli, only term EVs inhibited secretion of IL-6 in HIECs, and reduced expression of pro-inflammatory cytokine IL-1β in macrophages. Term and preterm EVs inhibited secretion of IL-1β and reduced inflammasome related cell death. We proposed that human milk EVs regulate immune-related signaling via their conserved microRNA cargo, which could promote tolerance and a homeostatic immune response. These findings provide basis for further studies into potential therapeutic supplementation with EVs in vulnerable newborn populations by considering functional, gestational age-specific effects. IMPACT: This study reveals distinct functional differences between term and preterm transitional human milk extracellular vesicles (EVs) highlighting the importance of gestational age in their bioactivity. Term EVs uniquely inhibited IL-6 secretion, IL-1β expression, and apoptosis following inflammatory stimuli. Both term and preterm human milk EVs reduced IL-1β secretion and inflammasome-induced cell death. Conserved human milk extracellular vesicle microRNA cargo could be a mediator of the anti-inflammatory effects, particularly targeting cytokine production, the inflammasome, and programmed cell death. These findings underscore the importance of considering gestational age in future research exploring the therapeutic potential of human milk extracellular vesicles to prevent or treat intestinal inflammatory diseases in neonates.

Optimization and evaluation of gastroresistant microparticles designed for siRNA oral delivery

Oral administration of siRNA is a challenging strategy for the local treatment of intestinal diseases, including cancer and inflammatory bowel disease. Both nucleic acids and delivery systems, especially lipid nanoparticles (LNPs), are sensitive to the acidic pH of the stomach, bile salts and digestive enzymes. The present work focuses on the design and evaluation of gastroresistant alginate microparticles (MPs) prepared with an original process for oral delivery of siRNA. MPs with a mean diameter of less than 200 µm were obtained without extrusion and emulsification methods. Onpattro® marketed pharmaceutical product and TNF-α siRNA-loaded LNPs were successfully microencapsulated with an efficiency of at least 80 %. Gastroresistance properties and intestinal release were demonstrated in simulated gastric and intestinal fluids. After exposure to simulated gastric fluid, MPs in contact with hepatocyte and LPS-activated monocyte-derived macrophage cell lines reduced the expression of transthyretin and TNF-α, demonstrating the preservation of the siRNA activity.

Intestinal failure-associated liver disease model: a reduced phytosterol intravenous lipid emulsion prevents liver injury.

Long-term parenteral nutrition in children often results in intestinal failure-associated liver disease (IFALD). Phytosterols are plant steroids in vegetable oil-based intravenous lipid emulsions (ILEs) that are associated with IFALD. We investigated whether a phytosterol-depleted soybean oil ILE, compared to standard soybean oil ILE, prevented hepatotoxicity in a murine IFALD model. Eight-week-old male C57BL/6 J mice were provided a fat-free high carbohydrate liquid dietfor 19 days. Mice were intravenously administered ILEs as the sole fat source: Intralipid® (commercially available soybean oil ILE), Omegaven® (commercially available fish oil ILE), a low phytosterol soybean oil ILE (L-SOLE) or a high phytosterol soybean oil ILE (H-SOLE) with matched alpha tocopherol content. On days 6, 12, and 18 mice were administered escalating intraperitoneal doses of lipopolysaccharide. Compared to chow controls, mice that received Intralipid® demonstrated elevated plasma biomarkers of liver injury and histologic liver disease (hepatosteatosis, histologic inflammation, F4/80 staining). L-SOLE prevented both biochemical and histologic liver injury. Administration of H-SOLE also prevented biochemical liver injury, but not steatosis. The combination of phytosterol removal and alpha tocopherol supplementation may reduce the toxicity associated with parenteral use of soybean oil-based ILE. Low phytosterol soybean oil may be a valuable component in safer next generation ILEs. Half of children receiving long-term parenteral nutrition develop intestinal failure-associated liver disease (IFALD). Standard intravenous lipid emulsions (ILEs) in parenteral nutrition are vegetable oil based and high in phytosterols (plant steroids); no low phytosterol vegetable oil-based ILE is available. Phytosterols in ILEs are associated with IFALD. In this study, a new phytosterol-depleted soybean oil was utilized in a laboratory-generated ILE. Use of the phytosterol-depleted soybean oil ILE prevented liver injury in a murine model of IFALD. Phytosterol-depleted soybean oil may be utilized as a component of less toxic next-generation ILEs.

Enhanced anti-inflammatory effects and metabolic profiles of cyanidin-3-glucoside via nanoliposomal encapsulation in Caco-2 and RAW 264.7 co-culture system

Cyanidin-3-glucoside (C3G) has been found to prevent/treat intestinal disease and maintain gut homeostasis. Numerous studies have proved that nanoliposomes can improve the absorption and utilization of food nutrients. However, the impacts of C3G nanoliposomes (C3G-NL) are still unkown. This study investigated the effects of cyanidin-3-glucoside nanoliposomes (C3G-NL) on intestinal inflammation and permeability using a Caco-2/RAW264.7 co-culture model. ELISA and qPCR results showed that C3G-NL reduced pro-inflammatory markers, including TNF-α, IL-6, IL-8, cyclooxygenase-2, and inducible nitric oxide synthase, while inhibiting the NF-κB/MAPK pathway. C3G-NL also improved intestinal barrier integrity by increasing transepithelial electrical resistance and upregulating tight junction proteins (zonula occludens-1, occludin, claudin-1). Additionally, C3G-NL enhanced C3G metabolism, leading to the formation of intermediary metabolites like chalcone and dihydroflavonols, which contributed to the synthesis of other anthocyanins (delphinidin, peonidin, petunidin, malvidin, and pelargonidin). Overall, C3G-NL helps mitigate inflammation and restore tight junction integrity via metabolic regulation.