Search Results (446)

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation, epithelial barrier disruption and immune dysfunction. Alleviating and curing these pathological manifestations is the goal of IBD treatment. Despite substantial advances in targeted immunotherapies and anti-inflammatory strategies, achieving sustained intestinal mucosal healing remains a major clinical challenge. Dynamin-related protein 1 (Drp1) is a GTPase that mediates mitochondrial fission and plays a crucial role in maintaining the dynamic balance of mitochondrial morphology and function. In IBD, Drp1 expression is frequently upregulated and continuously activated, resulting in excessive fission and fragmentation of mitochondria. This mitochondrial dysregulation contributes to ATP depletion and excessive reactive oxygen species (ROS) production, thereby exacerbating disease progression and amplifying inflammatory signaling. This review highlights the distinctive role of Drp1 as an integrative node in IBD. Specifically, we connect mitochondrial dynamics with epithelial barrier failure, immune dysregulation, inflammatory cell death, and intestinal microenvironment remodeling. We further emphasize the potential relevance of Drp1 for biomarker-based patient stratification and mechanism-informed therapeutic targeting, thereby distinguishing this review from more descriptive accounts of mitochondrial dysfunction in intestinal inflammation. Full article

Intestinal dysfunction and parenteral nutrition (PN) can trigger a spectrum of liver disorders collectively referred to as intestinal failure-associated liver disease (IFALD), for which therapeutic options remain limited. In the present study, we investigated the modulatory effects of the bioactive xanthophyll carotenoid lutein in an in vitro IFALD model utilizing human THLE-2 hepatocytes exposed to lipopolysaccharide and Intralipid to mimic PN–associated inflammatory and metabolic stress. Because lutein is poorly water-soluble and patients receiving PN lack enteral intake of this compound, we also evaluated the cyto- and hemocompatibility of a human serum albumin–based lutein nanoformulation developed to enable intravenous administration. A bead-based multiplex immunoassay revealed that lutein attenuated dysregulation of inflammatory and metabolic signaling by modulating total and phosphorylated levels of MAPKs, NF-κB, Akt, STAT5, CREB, and p70S6K. Lutein also affected lipid metabolism–related gene expression, decreasing SREBF2 and restoring ABCA1 and PRKAA2 mRNA toward control levels, as determined by qPCR. Nanoformulated lutein, with a mean particle size of approximately 160 nm, was non-toxic in THLE-2 cells and exhibited hemocompatibility in a human erythrocyte hemolysis assay. Together, our findings provide both biological and technological rationale for further exploration of lutein-based strategies to mitigate IFALD in patients receiving PN. Full article

Porcine epidemic diarrhea virus (PEDV) causes lethal enteritis in neonatal piglets, yet the mechanisms underlying rapid intestinal injury remain unclear. In particular, it is unknown whether different regulated cell death pathways act separately or cooperatively to worsen mucosal damage. To address this question, we performed multi-omics analyses of infected intestinal tissues and found concurrent activation of pyroptosis and ferroptosis during PEDV infection. PEDV infection activated the Caspa-se-1/GSDMD pathway in the duodenum and jejunum, as shown by generation of the Caspase-1 p20 fragment and cleavage of GSDMD into its active N-terminal form, indicating pyroptosis. At the same time, infected tissues displayed key features of ferroptosis, including weakened antioxidant defenses, increased lipid peroxidation, iron accumulation, lipid remodeling, and dysregulated ACSL4 and GPX4 expression. These two processes were closely linked and together contributed to tight junction disruption and barrier instability. Molecular docking further suggested that PEDV NSP1 and S proteins may interact with Caspase-1, providing a possible explanation for pyroptosis induction. Correlation analysis also showed strong associations between pyroptosis-related genes and ferroptosis-associated metabolites. Overall, our findings indicate that pyroptosis and ferroptosis cooperate to drive PEDV-induced intestinal inflammation and barrier damage, highlighting their joint inhibition as a potential strategy to reduce PEDV pathogenicity. Full article

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn’s disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings—including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis—can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD. Full article

Background: Short bowel syndrome (SBS) is a severe form of intestinal failure often associated with high output jejunostomy, fluid and electrolyte imbalance, and long-term dependence on parenteral nutrition (PN). In patients with type I SBS, restorative surgery may reduce PN dependence and enable conversion to type II or III SBS through restoration of intestinal continuity. Methods: We report our single-center experience. Between 2018 and 2025, nine adult patients with chronic type I SBS and high-output jejunostomy underwent restorative surgery within a multidisciplinary intestinal rehabilitation program. All patients were PN-dependent preoperatively, and two had intestinal failure-associated liver disease (IFALD). Surgical strategies were individualized according to residual anatomy and focused on restoration of intestinal continuity, without bowel lengthening procedures. Clinical outcomes were descriptively analyzed. Results: Intestinal continuity was successfully restored in all patients, resulting in conversion from type I to type II or III SBS. A clinically relevant improvement in intestinal function was observed in all cases, although follow-up duration was heterogeneous (range 3–60 months), with some patients still in early postoperative follow-up. Complete enteral autonomy was achieved in 3/9 patients (33%), while 6/9 patients (67%) experienced a reduction in PN requirements, including partial or nocturnal supplementation. Five of nine patients developed postoperative complications: one required reoperation and one endoscopic treatment for anastomotic bleeding. No 90-day postoperative mortality was recorded. Conclusions: In adult patients with type I SBS, restorative surgery enables anatomical and functional conversion to type II or III SBS. When performed within specialized multidisciplinary programs and guided by careful management of hostile abdomen, this approach may result in functional improvement and reduced PN dependence, although outcomes remain heterogeneous. Full article

Personalized medicine is increasingly shaping the management of inflammatory bowel disease (IBD), with the goal of tailoring diagnostic and therapeutic strategies to individual patients. Intestinal ultrasound (IUS) has emerged as a pivotal, non-invasive, and repeatable tool for assessing disease activity, treatment response, and complications in both Crohn’s disease and ulcerative colitis. Beyond its role in routine monitoring, IUS enables real-time decision-making and facilitates tight control strategies, aligning with the principles of precision medicine. By combining morphological assessment with advanced techniques, such as contrast-enhanced ultrasound and elastography, IUS offers unique opportunities for risk stratification and individualized treatment planning. Moreover, its accessibility, safety, and patient acceptability make IUS particularly suited for longitudinal follow-up and early detection of therapeutic failure, thereby reducing the need for invasive procedures. This review discusses the integration of IUS into personalized IBD care pathways, highlighting current evidence, clinical applications, and future perspectives. Full article

Background: This study aimed to investigate, from a scientific and formulation perspective, an oral semaglutide tablet incorporating sodium caprate (C10) as an intestinal absorption enhancer and to optimize its formulation performance using a Quality by Design (QbD)-based approach. Semaglutide—a peptide-based therapeutic—provides effective glycemic control and weight reduction; however, its extremely low oral bioavailability has limited administration to subcutaneous injection. Although various attempts have been made to improve peptide absorption, achieving consistent delivery through oral routes remains a significant challenge due to enzymatic degradation and poor membrane permeability. Methods: To overcome these limitations, an absorption enhancer (sodium caprate) was incorporated to enhance oral absorption, and a Quality by Design (QbD)-based approach was applied to systematically guide formulation development. Following the definition of the Quality Target Product Profile and critical quality attributes, risk assessments (Preliminary Hazard Analysis and Failure Mode and Effects Analysis) were conducted to identify key formulation factors. A design of experiments approach was then employed to determine the optimal tablet composition. Results: Consequently, the resulting formulation met all predefined quality criteria, including hardness, disintegration, friability, and content uniformity. In addition, the in vitro dissolution profile demonstrated a release pattern comparable to that of the reference product, with similarity factor values of 74.4, 74.7, and 71.3 at pH 1.2, 4.0, and 6.8, respectively. Conclusions: These findings indicate that the formulation can achieve consistent and reproducible quality performance as an oral semaglutide dosage form. The QbD-based formulation design strategy presented in this study provides a robust and broadly applicable approach for developing oral delivery systems for peptide drugs, including semaglutide, and ultimately provides useful formulation insight for future peptide-based oral delivery research. Full article

Necrotizing enterocolitis (NEC) is a major cause of illness and death in preterm infants and is increasingly linked to long-term neurodevelopmental issues among survivors. Usually seen as a gastrointestinal disease, NEC is rarely viewed from a brain-centered perspective. In this Perspective, we suggest that NEC should be understood as a disorder of the gut–brain axis affecting neurodevelopment. We combine clinical and experimental evidence showing that intestinal inflammation, microbial imbalance, epithelial barrier failure, and systemic immune activation during NEC all contribute to the disruption of early brain development. We contend that neurodevelopmental damage is a key feature of NEC rather than just a secondary effect of prematurity. Recognizing NEC as a gut–brain axis disorder is crucial for research models, treatment approaches, and assessing long-term outcomes in affected infants. Full article

Phosphatidylserine (PS) is an anionic phospholipid that is exposed to the outer leaflet of the cell membrane during apoptosis. This PS externalization can teach the immune system to tolerate an antigen without eliciting immunological consequences. Previously, we showed that mice treated with PS nanoparticles containing single-chain PS (LysoPS) induced oral tolerance towards therapeutic proteins, whereas double-chain PS did not. These observations suggest that structural alterations of PS play a critical role in its tolerogenic potential. Given that intestinal microfold cells (M-cells) facilitate the transport of particulate antigens from the intestinal lumen to Peyer’s patches (PP) for immune surveillance, we hypothesized that the failure of double-chain PS to induce tolerance may result from insufficient uptake by M-cells. The M cell-mediated uptake was investigated using in vitro and ex vivo studies and oral tolerance towards ovalbumin (OVA) was studied in M-cell-deficient mice. Consistent with this hypothesis, our data showed that LysoPS nanoparticles displayed at least a 2-fold increase in immune cell exposure and M-cell-mediated uptake compared to double-chain PS-containing nanoparticles. Importantly, LysoPS-mediated oral tolerance was absent in M cell-deficient mice with higher anti-ova antibody titers than the wild-type strain. These studies demonstrate that higher PS exposure on LysosPS nanoparticles compared to double chain could play a significant role in M cell-mediated tolerance. Full article

Heart failure (HF) is a systemic syndrome in which cardiac dysfunction is closely linked to multiorgan involvement, including the gastrointestinal tract. Increasing evidence highlights the relevance of the gut–heart axis in HF pathophysiology, whereby intestinal hypoperfusion, congestion, and barrier dysfunction promote gut microbiota dysbiosis, systemic inflammation, and adverse cardiovascular outcomes. In parallel, the advent of novel HF therapies, particularly sodium–glucose cotransporter 2 inhibitors (SGLT2i) and the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan, has markedly improved clinical outcomes across HF phenotypes. Beyond their established cardiovascular benefits, these therapies may exert pleiotropic effects that extend to the intestinal environment and the gut microbiota. Through integrated actions on hemodynamics, neurohormonal activation, metabolic pathways, and inflammatory processes, recent data suggest that novel HF drugs may indirectly influence the gut-microbial composition and function. Conversely, the gut microbiota may modulate drug efficacy and result in interindividual variability in therapeutic responses, suggesting a bidirectional interaction between pharmacological treatment and the gut ecosystem. This narrative review summarizes current evidence of gut microbiota alterations in HF and critically examines emerging data on interactions between the gut microbiota and novel HF therapies, focusing on SGLT2 inhibitors and sacubitril/valsartan. Understanding this crosstalk may support the development of microbiota-informed, personalized therapeutic strategies in heart failure. Full article

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson’s disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to 30 November 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only one dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. From Vpre to Vpost, “Off” time was reduced in 2.9 ± 1.9 h (p = 0.002) and motor symptoms burden improved significantly (p = 0.013), whereas a trend of significance was found for non-motor symptoms burden (p = 0.050) and quality of life (p = 0.126). Conclusions: LECIG could be an alternative therapeutic option in PwP who failed fLD/fCD. Full article

Background: Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure and is frequently associated with long-term dependence on parenteral nutrition (PN) and intravenous fluids. Teduglutide, a glucagon-like peptide-2 (GLP-2) analogue, promotes intestinal adaptation and has been demonstrated to reduce parenteral support requirements. However, real-world data from the Greek population are scarce. Methods: We conducted a non-interventional, multicenter, retrospective cohort study across 5 centers in Greece, including adult patients with SBS receiving teduglutide therapy. Demographic and clinical characteristics, parenteral nutrition and intravenous fluid requirements, body mass index (BMI), laboratory parameters, and adverse events were recorded at baseline and during follow-up at weeks 4, 12, 26, and 52. Results: Eight adult patients with SBS were included (75% female), with a median age of 53 years (range 19–71). Over 52 weeks of treatment, mean parenteral nutrition requirements decreased by approximately 45% compared with baseline (from 1430 to 788 kcal/day), while mean intravenous hydration requirements decreased by approximately 80% (from 5170 to 1000 mL/week). Complete independence from parenteral nutrition was achieved in 2 of 8 patients (25%). Nutritional status improved, with a 10.6% increase in mean BMI at Week 52. Teduglutide was generally well tolerated; mild adverse events occurred in 3 of 8 patients, were predominantly gastrointestinal, and did not lead to treatment discontinuation. Conclusions: This study provides data from the Greek population and supports the effectiveness and favorable safety profile of teduglutide in adult patients with SBS and chronic intestinal failure. Further prospective studies are warranted to better define predictors of response and optimize long-term management strategies. Full article

Background: Pediatric Short bowel syndrome (SBS) is the leading cause of intestinal failure and is characterized by persistent dysbiosis that negatively impacts intestinal adaptation and growth. Although microbiota modulation via pre-, pro-, and synbiotics represents a promising strategy, current evidence remains fragmented. This narrative review aims to critically assess the efficacy and safety of such interventions in the management of pediatric SBS. Methods: A structured literature search was conducted on PubMed up to November 2025. Fourteen relevant studies were included, comprising clinical trials, preclinical animal models, and significant case reports regarding the use of biotics in SBS. Results: The analysis reveals a microbiological dichotomy based on nutritional status: parenteral nutrition (PN)-dependent patients exhibit an excess of Proteobacteria associated with infectious risk, whereas weaned patients present a metabolic risk of D-lactic acidosis due to carbohydrate fermentation. Regarding efficacy, long-term synbiotic treatments (>12 months) demonstrated significant improvements in growth and nutritional status, likely mediated by increased production of short-chain fatty acids (SCFAs) and mucosal adaptation, unlike short-term probiotic cycles. However, serious adverse events (Lactobacillus sepsis and D-lactic acidosis) were reported, predominantly in patients with central venous catheters or malabsorption. Conclusions: Biotics offer therapeutic potential for intestinal failure, but their use cannot be empirical. The safety profile should be carefully selected, especially in central venous catheter (CVC) carriers. Future strategies must evolve towards precision medicine, prioritizing non-D-lactate-producing strains and personalized protocols based on the patient’s nutritional phase. Full article

Short bowel syndrome (SBS) develops when the remaining intestine is unable to sustain adequate nutrient and electrolyte absorption following extensive bowel resection. The condition is characterized by malabsorption and significant fluid losses which lead to dehydration and progressive weight loss, thus promoting patient dependence on parenteral fluids or nutrition. After an initial acute phase marked by accelerated intestinal transit and gastric hypersecretion, long-term clinical outcomes are largely determined by the capacity of the remaining bowel for intestinal adaptation—a sustained process of structural, functional, and molecular remodeling that enhances absorptive efficiency and restores fluid and nutrient homeostasis. This review summarizes the key histological and cellular features of the adaptive response, including crypt and villus remodeling, mucosal hyperplasia, and smooth muscle hypertrophy, and integrates emerging concepts in crypt biology that define the dynamic cross-talk between intestinal stem cells and the mesenchymal niche, together with their upstream regulatory pathways. Full article

Objective: This study aimed to describe the main microorganisms causing catheter-related bloodstream infections (CRBSIs) and to evaluate the effectiveness of taurolidine catheter lock therapy in children with intestinal failure (IF) receiving parenteral nutrition (PN). Study design: This retrospective study included 31 pediatric patients with IF admitted between 2017 and 2022 who received PN via central venous catheters (CVCs). Demographic, clinical, and laboratory data were collected, along with information on PN use, catheter characteristics, and infection episodes, including clinical signs, microbiological cultures, and antimicrobial therapy. Serum C-reactive protein and albumin levels, as well as the use of taurolidine lock therapy, were analyzed. Results: The median age was 54.4 days among patients who developed CRBSI and 154.1 days among those without CRBSI. The median duration of PN was 119 days in patients with CRBSI and 89 days in those without. Nineteen patients experienced CRBSI, accounting for 55 infection episodes confirmed by blood cultures obtained from CVCs. The most frequently isolated microorganisms were Staphylococcus epidermidis, Enterococcus faecalis, and Klebsiella pneumoniae. Taurolidine lock therapy was significantly associated with lower infection rates per 1000 catheter days, with most infected catheters and infection episodes occurring in the absence of taurolidine use. Conclusions: These findings contribute to the characterization of the microbiological profile of CRBSIs in pediatric patients with IF and support the use of advanced preventive strategies, such as taurolidine lock therapy, to reduce infection rates in children receiving long-term PN. Full article