Search Results (51)

Background/Objectives: Anastomoses under tension are associated with anastomotic leaks and strictures. In experimental surgery, anastomoses are frequently tested for their resistance to traction forces, but without the surgically untouched organ as a comparator. We therefore investigated whether and to what extent the breaking forces along the gastrointestinal tract differed in the intact intestinal organs to provide some data for the comparison of anastomoses to it and guide sample size estimation in the mouse. Methods: We included 54 mice of the Crl:CD1(ICR) stock and, as a comparator, 10 mice of the C57Bl/6J and 10 mice of the C57Bl/6NCrl strain of both sexes. We determined breaking forces using a motorised test stand. Results were compared via estimated marginal means with a control of the false-discovery rate by the Benjamini–Hochberg procedure. Results: In all mice strains, the resistance to traction forces was in a descending manner: stomach (mean (µ) ≥ 1.87 Newtons, standard deviation (σ) ≤ 0.63) > rectum(µ > 1.31 Newtons, σ ≤ 0.63) > caecum (µ > 1.1 Newtons, σ ≤ 0.37) > colon(µ > 0.93 Newtons, σ ≤ 0.31) > duodenum (µ > 0.65 Newtons, σ ≤ 0.28) > jejunum (µ > 0.5 N, σ ≤ 0.16) > ileum (µ ≥ 0.43 Newtons, σ ≤ 0.13). The analysis of variance showed a statistically significant effect of the mouse strain on breaking forces (F(2,497) = 16.81, p < 0.001). This was also the case for the investigated organ (F(6,497) = 104.18, p < 0.001) and the interaction between strain and organ (F(12,497) = 2, p = 0.022), indicating a difference between strains. Only the stomachs differed between the included strains; the stomach of Crl:CD1(ICR) sustained −0.81 Newtons (t = −6.23, p < 0.001) compared to those of C57Bl/6J, and −0.37 Newtons (t = −2.88, p = 0.006) compared to those of C57Bl/6NCrl. Other statistically significant differences were absent. Conclusions: Differences in breaking forces between inbred strains and outbred stock were only present for the stomach. Our results may provide a first baseline of breaking force measurements for other studies investigating anastomoses and the respective sample size analyses. Full article

This detailed narrative review focuses on the current understanding of unique alterations in GM colonization and subsequent complications following surgery for significant childhood conditions, such as necrotizing enterocolitis (NEC), Hirschsprung’s disease (HD), inflammatory bowel disease (IBD), and short bowel syndrome (SBS). Surgical interventions can alter the diversity and structure of the GM and potentially cause post-surgical complications. Although the data are well-established in adults, there is a lack of pediatric-specific data on post-surgical GM dysbiosis and its complications, including surgical infections, intestinal obstructions (IO), and anastomotic leak (AL). This gap constitutes both a clinical risk and an important therapeutic opportunity. Therefore, research on how to modulate the GM perioperatively in children is needed. Current research provides an initial understanding of the possible post-surgical implications for outcomes of these intestinal disorders. Future studies could clarify GM alterations associated with various pediatric intestinal surgical procedures and their complications, which may influence the evaluation of GM-targeted treatments. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental condition mainly characterized by social impairments and repetitive behaviors. An altered intestinal barrier morphology and increased transmucosal leaks have also been implicated in ASD; in fact, comorbidities such as gastrointestinal problems (leaky gut) have frequently been reported in these patients. The regulation of tight junctions (TJs) is essential in maintaining intestinal barrier morphology and in regulating the delicate balance of trafficking between the intestinal lumen and the submucosa. To date, there are no definitive treatments for ASD comorbidities; however, melatonin (MLT) represents a well-validated and tolerated treatment for sleep disorders in ASD patients. The potential beneficial effects of MLT on this disorder have been and continue to be better investigated. In this context, the present study examines the effects of oral MLT administration (10 mg/kg/day for 16 weeks) on the intestinal barrier in BTBR T + Itpr3tf/J (BTBR) mice, a validated ASD model. Morphological analyses of the ileum of these animals reveal modified villus height (Vh), crypt depth (Cd), and Vh–Cd ratios; an inflammatory state; and a decrease in Paneth cells. Moreover, these mice showed altered TJ expression compared to the control animals (C57BL6/J mice). Notably, MLT normalizes morphological indices and TJ expression, consistent with an improved gut barrier morphology. These data collectively suggest that orally administered MLT can promote the remodeling of the intestinal barrier; thus, we can suppose that MLT reduces gastrointestinal barrier leaks. The overall safety and economy of MLT use suggest that this indolamine could be efficacious as an adjuvant therapy to reduce the condition known as leaky gut. Full article

Impairment of the intestinal epithelial barrier, accompanied by local and systemic inflammation, underlies numerous human pathologies, including inflammatory bowel diseases, celiac disease, sepsis, as well as severe acute malnutrition. Bifidobacterium longum subsp. infantis and Lacticaseibacillus rhamnosus GG (LGG^®) have been shown in preclinical studies to strengthen the gut epithelial barrier and attenuate inflammation. This study aimed to compare the ability of four commercial strains of B. infantis, LGG, and their combination to mitigate inflammation-mediated epithelial damage using an in vitro immunocompetent intestinal model. A microfluidic mid-throughput platform OrganoPlate^® was used to co-culture intestinal epithelial cells (Caco-2) with peripheral blood mononuclear cells (PBMCs). Epithelial damage was induced by stimulating PBMCs with lipopolysaccharide (LPS), and probiotic-conditioned media were applied to the apical side of Caco-2 cells to assess effects on barrier integrity, cytokine secretion, and gene transcription. All tested probiotics significantly protected the epithelium by modulating tight junction protein expression and promoting transcription of homeostatic cytokines, resulting in a “leak-tight” phenotype. These findings indicate that metabolites produced by B. infantis and/or LGG can protect the intestinal epithelium in vitro, warranting further in vivo studies to evaluate the translational relevance of this effect. Full article

Acute pancreatitis (AP) is the most common cause of gastrointestinal-related hospitalizations in the United States, with gallstone disease and alcohol as the leading etiologies. Management is determined by disease severity, classified as interstitial edematous pancreatitis or necrotizing pancreatitis, with severity further stratified based on local complications and systemic organ dysfunction. Regardless of etiology, initial treatment involves aggressive intravenous fluid resuscitation with Lactated Ringer’s solution, pain and nausea control, early oral feeding in 24 to 48 h, and etiology-directed interventions when indicated. In gallstone pancreatitis, early endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy is indicated in the presence of concomitant cholangitis or persistent biliary obstruction, with subsequent laparoscopic cholecystectomy as standard of care for stone clearance. The role of interventional therapy in uncomplicated AP is limited in the acute phase, except for biliary decompression or enteral feeding support with nasojejunal tube placement. However, in severe AP with complications, interventional radiology (IR) and endoscopic approaches play a pivotal role. IR facilitates early percutaneous drainage of symptomatic, acute fluid collections and infected necrosis, particularly in non-endoscopically accessible retroperitoneal or dependent collections, improving outcomes with a step-up approach. IR-guided angiographic embolization is the preferred modality for hemorrhagic complications, including pseudoaneurysms. In the delayed phase, walled-off necrosis (WON) and pancreatic pseudocysts are managed with endoscopic ultrasound (EUS)-guided drainage, with direct endoscopic necrosectomy (DEN) reserved for infected necrosis. Dual-modality drainage (DMD), combining percutaneous and endoscopic drainage, is increasingly utilized in extensive or complex collections, reflecting a collaborative effort between gastroenterology and interventional radiology comparable to that which exists between IR and surgery in institutions that perform video assisted retroperitoneal debridement (VARD). Peripancreatic fluid collections may fistulize into adjacent structures, including the stomach, small intestine, or colon, requiring transpapillary stenting with or without additional closure of the gut leak with over-the-scope clips (OTSC) or suturing devices. Additionally, endoscopic management of pancreatic duct disruptions with transpapillary or transmural stenting plays a key role in cases of disconnected pancreatic duct syndrome (DPDS). Comparative outcomes across interventional techniques—including retroperitoneal, laparoscopic, open surgery, and endoscopic drainage—highlight a shift toward minimally invasive approaches, with decreased morbidity and reduced hospital stay. The integration of endoscopic and interventional radiology-guided techniques has transformed the management of AP complications and multidisciplinary collaboration is essential for optimal patient outcomes. Full article

This study focuses on the issue of whether orally administered zinc (gluconate) (26 mg BID) can induce the remodeling of gastrointestinal barrier function and reduce passive leak across the human intestinal mucosal barrier in situ. Increased transmucosal leak has been implicated in diseases as diverse and seemingly unconnected as Inflammatory Bowel Disease (IBD), Celiac Disease, Autism Spectrum Disorders and Alzheimer’s Dementia. Our current investigation represents the first patient-based study to examine the effect of zinc on gastrointestinal epithelial tight junctions and gastrointestinal barrier leak in otherwise healthy test subjects. Using independent test subject groups for each endpoint, three separate molecular analyses indicated that zinc treatment can achieve a positive outcome: (1) RNA-seq analyses of intestinal biopsies showed salutary patterns of gene transcription changes dealing with not only transcripts of junctional proteins but also transcripts mitigating the proinflammatory state, as well as dedifferentiation (both modulators of tight junction permeability); (2) Western immunoblot analyses of intestinal tissue indicated that tight junctional protein expression was being modified by the administered zinc, most notably Claudin-2 and Tricellulin; (3) zinc treatment induced a reduction in serum levels of a functional marker of passive intestinal leak, namely the GI microbiome metabolite D-Lactate. The data collectively suggest that orally administered zinc can induce remodeling of the intestinal epithelial barrier, resulting in the reduction in GI barrier leak. The overall safety and economy of supplement levels of zinc suggest that this micronutrient could be efficacious as an adjuvant therapy to reduce the condition known as leaky gut, and possibly therefore be protective regarding diseases postulated to involve leaky gut. Full article

A 62-year-old female presented to the Emergency Department of the General Hospital of Katerini, Greece, complaining of abdominal pain, fever, and general discomfort. Laboratory tests indicated an elevated white blood cell count and an elevated C-reactive protein level. A computed tomography (CT) scan revealed dilated small bowel loops and free intraperitoneal fluid. During laparotomy, extensive ischemia and necrosis of both the small and large bowel were discovered, and a resection of the small bowel and the right colon was performed, leaving the patient with only 90 cm of small intestine and a jejunocolic anastomosis. Postoperative management was particularly challenging, requiring a multidisciplinary approach, an intensive care unit stay, reoperations due to anastomotic leaks, continuous parenteral nutrition and electrolyte management, and aggressive antibiotic treatment for persistent bacterial infections. This case report highlights the importance of appropriate management of this life-threatening complication following extensive bowel resection. Full article

Background: Whether intestinal epithelial cells can regulate distant adipose tissue remains a mystery. Methods: Cold-stimulated intestinal epithelial cell-derived exosomes (Cold IEC-Exo) play a pivotal role in enhancing adipose thermogenesis and metabolic homeostasis, as demonstrated in this study. Results: IEC-Exo can accumulate in adipose tissue. Compared with IEC-Exo derived from room temperature mice (RT IEC-Exo), Cold IEC-Exo significantly enhanced the thermogenesis of adipose. In vitro, Cold IEC-Exo directly stimulated thermogenesis in primary adipocytes by elevating oxygen consumption rate, proton leak, and fatty acid uptake, with no effect on glucose uptake. Small RNA sequencing identified miR-674-3p as a key mediator enriched in Cold IEC-Exo. miR-674-3p mimicry replicated Cold IEC-Exo effects, augmenting Ucp1 expression, mitochondrial uncoupling, and fatty acid utilization in adipocytes. Local overexpression of miR-674-3p in BAT and sWAT via AAV in vivo enhanced thermogenesis and attenuated diet-induced glucose intolerance. Conclusions: These findings establish that Cold IEC-Exo, via miR-674-3p transfer, drive adipose thermogenic activation and mitigate metabolic dysfunction, highlighting their therapeutic potential in obesity-related disorders. Full article

Background and Objectives: Colonic anastomotic leaks are still a critical cause of morbidity and mortality. The study aimed to investigate the effects of esomeprazole on anastomotic healing after left colon anastomosis in rats with an ischemic colon. Material and Methods: Thirty-five male Wistar albino rats were divided into acute (CONTROL-A, ESP-A) and chronic (CONTROL-C, ESP-C) stage groups. Rats in the CONTROL-A and CONTROL-C groups underwent colonic anastomosis after hypoxia-reperfusion injury in the colon, and intraperitoneal saline was administered for three and ten days, respectively. Intraperitoneal 10 mg/day esomeprazole was given to the rats in the ESP-A and ESP-C groups for three and ten days after similar surgical procedures. Then, at scheduled times, 2 cm proximal and distal regions of the anastomosis line were resected, and bursting pressure was measured. Hydroxyproline (HYP), myeloperoxidase (MPO), malondialdehyde (MDA), caspase-3 (CSP3) and catalase (CAT), nitric oxide (NO), reduced glutathione (RGT), superoxide dismutase (SOD), TNF-α, IL-6, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels were measured in tissue and blood serum samples. Results: In the acute stage, CAT, NO, RGT, and SOD values in ESP-A group were lower than CONTROL-A group values. In addition, TNF, IL-6, ALT, and AST values in the ESP-A group were higher than the CONTROL-A group values between groups (p < 0.05). However, HYP and burst pressure values were not different between the groups. In the chronic stage, CAT, NO, RGT, SOD, CSP3, and burst pressure values in the ESP-A group were higher than CONTROL-A group values (p = 0.05). In contrast, TNF, IL-6, ALT, AST, HYP, MPO, and MDA values in the ESP-A group were lower than the CONTROL-A group values (p < 0.05). Conclusions: These results suggest that esomeprazole has anti-inflammatory and antioxidant activity in the chronic phase of ischemia–reperfusion injury, thus protecting the intestinal tissue from ischemic damage and enhancing the healing of the anastomosis line. Full article

Background: Vascular Ehlers–Danlos syndrome (vEDS) is a rare connective tissue disorder characterized by collagen type III deficiency, predisposing to spontaneous arterial, uterine, and intestinal ruptures. While intestinal complications are recognized in vEDS, intestinal failure (IF) secondary to these complications is a rare and potentially life-threatening occurrence. This study aimed to describe the clinical presentation, surgical management, and outcomes of pediatric patients with IF secondary to vEDS and to provide a comprehensive review of the limited existing literature on this challenging clinical scenario. Methods: This study comprises a case series of pediatric patients with IF due to vEDS complications and a comprehensive literature review. Clinical data were collected from medical records, including age at diagnosis, surgical history, complications, nutritional status, and long-term outcomes. A literature review was performed to identify studies reporting gastrointestinal complications, surgical outcomes in pediatric vEDS patients, and cases of intestinal failure. Results: Two pediatric patients with vEDS and IF were included. Both patients experienced intestinal perforations and surgical complications and required long-term parenteral nutrition (PN). One patient required PN for 18 months before achieving enteral autonomy, while the other remains dependent. The literature review included four articles and revealed a high risk of complications, including anastomotic leaks, fistulae, and recurrent perforations, in patients with vEDS undergoing intestinal surgery. Delayed diagnosis of vEDS was common. Conclusions: Intestinal complications in pediatric patients with vEDS can lead to severe short bowel syndrome and long-term PN dependence. Early diagnosis and a multidisciplinary approach are crucial for optimizing patient care and minimizing complications. Full article

Objective: It is well established that having a stoma can negatively impact health-related quality of life (HRQoL), but there is a paucity of research describing the natural history of certain complications associated with living with a stoma, such as leakage and peristomal skin complications (PSCs), and whether these affect QoL within the first year of stoma surgery. The objective of this study was to investigate the pattern of such complications and impact on QoL in individuals who had stoma surgery within the preceding year. Methods: A cross-sectional study was conducted at three hospital sites in the United Kingdom to evaluate the burden of disease in those who had undergone intestinal stoma formation surgery within the preceding year. The study consisted of a one-to-one consultation with a study nurse and the completion of an online questionnaire by the patient (ISRCTN-registry: 23080097). The nurse-led interview directly evaluated peristomal skin health, whilst the online questionnaire evaluated the impact of leakage (using the Ostomy Leak Impact tool), generic mental well-being (by WHO-5) and wider HRQoL (by EQ-5D-5L). Results: A total of 114 individuals with an intestinal stoma completed the evaluations. The participants had a mean age of 55.8 years (range 18–87 years) and 58% were male. Forty-three percent of the participants had experienced leakage of stomal effluent outside the baseplate (e.g., onto clothes) in the preceding two weeks and 85% suffered from PSCs ranging from mild (35%), to moderate (18%), and severe (32%). Leakage and PSCs were associated with lower mental well-being and HRQoL (p < 0.05). Leakage events, HRQoL, mental well-being and peristomal skin health were similar for individuals across different timepoints from the time of surgery within the first year. Conclusions: This study reported a high disease burden in people with a new intestinal stoma. Experiencing frequent leakage incidents and/or living with severe PSCs were associated with reduced HRQoL and mental well-being. Full article

Anastomotic leaks remain a significant challenge in intestinal surgery, often leading to severe complications. This study investigated a novel approach to enhance anastomotic healing and reduce the risk of leaks by combining traditional suturing and stapling techniques with non-thermal atmospheric pressure plasma (NTAPP) application. NTAPP, a cold atmospheric plasma generated through the ionization of ambient air, has been shown to possess antimicrobial, hemostatic, and wound-healing properties. NTAPP promotes sterilization, coagulation, and tissue regeneration by generating reactive oxygen and nitrogen species, potentially strengthening anastomotic union. This pilot study evaluated the efficacy of NTAPP in three patients undergoing intestinal anastomosis. Following the standard surgical procedure, NTAPP was applied directly to the anastomotic site. Postoperative outcomes were monitored for six months, including anastomotic leaks and healing rates. Preliminary results demonstrated promising outcomes. All three patients exhibited successful sealing of the anastomosis, with no evidence of leakage during the follow-up period, providing reassurance and confidence in the potential of sutures, staples, and NTAPP. These findings suggest that NTAPP can significantly improve the safety and efficacy of intestinal surgeries by reducing the incidence of anastomotic leaks. While further research with a larger sample is necessary to confirm these initial findings, the results of this study provide a strong foundation for exploring the potential of NTAPP as a valuable adjunct to conventional surgical techniques for preventing anastomotic leaks. This innovative approach could reduce postoperative complications, improve patient outcomes, and enhance the overall quality of care in intestinal surgery. Full article

α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds’ effect on enzymatic activity, their molecular modeling on α-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as α-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, α-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome. Full article

Background: The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been extensively described, the intestinal healing process is still not fully understood. There are some similarities but also some differences compared to other tissues. The aim of this systematic review was to summarize all studies with knockout (KO) experimental models in bowel anastomoses, underline any recent knowledge, and clarify further the cellular and molecular mechanisms of the intestinal healing process. A systematic review protocol was performed. Materials and methods: Medline, EMBASE, and Scopus were comprehensively searched. Results: a total of eight studies were included. The silenced genes included interleukin-10, the four-and-one-half LIM domain-containing protein 2 (FHL2), cyclooxygenase-2 (COX-2), annexin A1 (ANXA-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and heparin-binding epidermal growth factor (HB-EGF) gene. Surgically, an end-to-end bowel anastomosis was performed in the majority of the studies. Increased inflammatory cell infiltration in the anastomotic site was found in IL-10-, annexin-A1-, and TAFI-deficient mice compared to controls. COX-1 deficiency showed decreased angiogenesis at the anastomotic site. Administration of prostaglandin E2 in COX-2-deficient mice partially improved anastomotic leak rates, while treatment of ANXA1 KO mice with Ac2-26 nanoparticles reduced colitis activity and increased weight recovery following surgery. Conclusions: our findings provide new insights into improving intestinal wound healing by amplifying the aforementioned genes using appropriate gene therapies. Further research is required to clarify further the cellular and micromolecular mechanisms of intestinal healing. Full article

Astaxanthin was encapsulated in liposomes by a thin layer dispersion and ultrasound method using soybean phospholipid. The digestion properties of liposomes for encapsulating astaxanthin were investigated in light of particle size, size distribution, zeta potential, and microstructure during in vitro digestion as a function of time. These results exhibited that the average particle size increased gradually with liposomal vesicles retained round shapes and a fairly uniform distribution after passage through the simulated gastric fluid digestion. The result revealed that astaxanthin-loaded liposomes were stable in low pH conditions. It was also found that the mixed micelles formed in a simulated intestinal fluid. The zeta potential of astaxanthin-loaded liposomes had a decrease in negativity after digestion. In comparison with free astaxanthin, there was an appreciable increase in the bioaccessibility of astaxanthin after encapsulation in liposomes. This enhancement can be attributed to more soluble astaxanthin in the mixed micelles for astaxanthin-loaded liposomes. It indicated that the barrier of the liposomal bilayer could inhibit astaxanthin fading and leaking after encapsulation in liposomes. These results provide useful information for designing more stable delivery systems in the gastrointestinal tract and improving the bioaccessibility of lipophilic nutraceuticals. Full article