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Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. There is a significant burden of mortality from colorectal cancer in Africa. Due to the heterogeneity of dietary and lifestyle practices throughout Africa, our work sought to define risk factors for the development of CRC in the African continent., Methods: We systematically searched PubMed, Embase, Global Health, CINAHL, Cochrane CENTRAL, and African Index Medicus for studies written in English, examining the incidence and risk factors of CRC in Africa. A systematic analysis was done to compare different risk factors in constituent studies. A meta-analysis random effects model was fitted to estimate the pooled incidence of CRC., Results: Of 2471 studies screened, 26 were included for the quantitative analysis; 20 in the incidence analysis, and six in the risk factor analysis. The overall ASIR per 100,000 person-years of CRC for males and females was 7.51 and 6.22, respectively. The highest incidence rates were observed between 2012 and 2021. Risk factors for CRC in Africa include tobacco smoking, and consumption of red meat, butter, and alcohol. Protective factors included, regular consumption of fruits and regular physical activity., Conclusion: The incidence of CRC in Africa is higher than that suggested by previous studies. Our study shows that nonmodifiable and modifiable factors contribute to CRC in Africa. High-quality studies conducted on generalizable populations that examine risk factors in a comprehensive fashion are required to inform primary and secondary prevention initiatives for CRC in Africa., (© 2024. The Author(s).)

Study Objective: a To identify the type of endometriosis education and surgical training colorectal surgery residents are exposed to during training b To determine the current surgical management of endometriosis among recently graduated colorectal surgeons and their level of comfort., Design: A qualitative cross-sectional study was performed. An anonymous questionnaire was emailed to colorectal surgery residents of 2023 and recent graduates for completion. Data was then extracted and analyzed from REDCap. A chi-square test was performed on the primary outcome variables., Setting: A REDCap electronic survey was administered through email to each participant., Patients: All colorectal surgery residents in 2023 and recent graduates from Colon and Rectal Surgery subspecialty from 2012 to 2022., Interventions: A 17-item anonymous questionnaire was sent via email through REDCap MEASUREMENTS AND MAIN RESULTS: The survey was completed by 70 participants. Most respondents (58.5%) did not receive formal education on bowel endometriosis. Forty percent of participants (28/70) did not feel they received adequate training for surgical management of bowel endometriosis. In terms of surgical exposure, 3.8% (2) responded they had been involved in > 15 bowel endometriosis cases and 18 (25.7%) had been exposed to 1-5 cases during colorectal training. Factors that predicted feeling adequately trained in managing endometriosis included formal endometriosis education (OR 4.70, 95% CI 1.37-16.12, p-value .027) and surgical exposure during training (OR 4.38, 95% CI 1.18 - 16.26, p-value .014). Additionally, the number of cases exposed during training is highly correlated with feeling adequately trained., Conclusion: More than half of colorectal surgeons did not receive formal education on bowel endometriosis and the majority had only been exposed to 1-5 cases during their colorectal training. An overwhelming majority were interested in further education. This study highlights opportunities for improvement in the exposure to education and surgical management of endometriosis among colorectal surgery trainees., Competing Interests: Disclosure statement The authors declare that they have no conflicts of interest and nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Recto-colic graft-versus-host disease (GVHD) is a frequent and serious complication of hematopoietic stem cell allogeneic transplantation, which is sometimes difficult to diagnose. The aim of our study was to identify histological diagnostic and prognostic criteria for recto-colic GVH., Material and Method: Patients allografted at Amiens university hospital from 2012 to 2017 were retrieved. Those who had a recto-colic biopsy were included and divided into two groups (final diagnosis of GVH and non-GVH), then biopsies were reviewed by 2 pathologists., Results: One hundred and nineteen patients were included. Sixty-seven were allocated to the GVH group and 52 to the non-GVH group. In the GVH group, we observed a significantly greater number of apoptotic bodies (AB) on standard HES staining and with the anti-Caspase 3 immunohistochemistry, cryptolytic AB abscesses, atrophy, regenerative glands and glands lined with eosinophilic cells (P<0.001). Anti-Caspase 3 immunohistochemistry revealed more AB than standard HES staining (P<0.005). But to differentiate GVH cases from non-GVH cases, we obtained a threshold value of 3.5 AB per 10 contiguous crypts on standard HE staining and with the anti-Caspase 3 immunohistochemistry. From 4 AB per 10 contiguous crypts, on HES staining and anti-Caspase 3 immunostaining, the diagnosis of GVH became consistent. No non-GVH case had more than 6 AB per 10 contiguous crypts. GVH patients with more than 8 AB per 10 contiguous crypts had a worse prognosis (P<0.001)., Conclusion: We confirm the value of AB and their counting in the diagnosis of GVH, with a diagnostic threshold of 4 AB and a prognostic threshold of 8 AB. Glands lined with eosinophilic cells could be an additional diagnostic criterion in favor of GVH to be confirmed by further studies., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pneumatosis cystoides intestinalis (PCI) is an uncommon condition characterized by the presence of a collection of individual gas cysts in the submucosa and subserosa of the intestine. The etiology of PCI is still unclear. We experienced 3 cases with PCI during treatment for pulmonary Mycobacterium avium complex (MAC) infection. Each case was treated conservatively. We believe our case series will highlight the importance of examining the gastrointestinal tract of patients with MAC infection and hopefully elucidate the clinical characteristics of PCI which developed during MAC treatment., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Pancreatic ductal adenocarcinoma (PDAC) remains a dreadful disease with poor prognosis. While the prognosis of colorectal carcinoma (CRC) is better than that of PDAC, it still is the second-leading cause of cancer deaths worldwide. Recently, a (methyl)lanthionine-stabilized, highly receptor-specific agonist of galanin subtype 2 (GAL2) receptor inhibited the growth of GAL2 receptor-expressing patient-derived xenografts (PDX) of pancreatic cancer. Furthermore, a lanthionine-constrained agonist of angiotensin II type 2 (AT 2 ) receptor inhibited PDX of colorectal cancer in mice. Stimulation of GAL2 receptor may modulate immune surveillance and inhibits PDAC via cell cycle inhibition and apoptosis. Consistent with GAL2 receptor-mediated tumor inhibition, for PDAC, survival is much higher for patients with high GAL2 receptor expression. Importantly, a (methyl)lanthionine-stabilized GAL2 receptor-specific agonist enhances expression of GAL2 receptor, not only in PDAC-PDX but also in healthy tissue indicating therapeutic and preventive potentials for GAL2 receptor agonists. AT 2  receptor is interacting with four tumor suppressor proteins, Src homology phosphatase 1, Src homology phosphatase 2, Promyelocytic Leukemia Zinc Finger protein and Microtuble-Associated Scaffold Protein1, the latter also known as Angiotensin-II type 2 receptor-Interacting Protein. Pathways linked to these tumor suppressor proteins may enhance immune surveillance, prevent carcinogenesis, counter proliferation and stimulate apoptosis. Taken together, current data are prompting the hypothesis of a prophylactic treatment option with stable, specific and safe agonists of GAL2 receptor and AT 2 receptor to prevent the emergence of pancreatic and colorectal cancer in individuals at risk., Competing Interests: Declaration of competing interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

The origin of vitamin D 2 in herbivorous animals was investigated in vivo in sheep and in bovine as well as mouse gastrointestinal tracts. A high concentration of 25-hydroxyvitamin D 2 in blood plasma of sheep both in summer and winter appeared to be incompatible with the undetectable level of vitamin D 2 in the pasture on which the sheep were grazing. Studies with bovine rumen contents from a cow grazing the same pasture as the sheep, demonstrated an increased concentration of vitamin D 2 on anaerobic incubation in a 'Rusitec' artificial rumen, which was further enhanced when cellulose powder was added as a fermentation substrate. The colon contents of mice that were fed from weaning on a vitamin D-free diet were found to contain vitamin D 2 . The results of these comparative studies in 3 animal species indicated that vitamin D 2 was being generated by microbial anaerobic metabolism in the gastrointestinal tract., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Keratin intermediate filaments form dynamic filamentous networks, which provide mechanical stability, scaffolding, and protection against stress to epithelial cells. Keratins and other intermediate filaments have been increasingly linked to the regulation of mitochondrial function and homeostasis in different tissues and cell types. While deletion of keratin 8 (K8 -/- ) in mouse colon elicits a colitis-like phenotype, epithelial hyperproliferation, and blunted mitochondrial ketogenesis, the role of K8 in colonocyte mitochondrial function and energy metabolism is unknown. We used two K8 knockout mouse models and CRISPR/Cas9 K8 -/- colorectal adenocarcinoma Caco-2 cells to answer this question. The results show that K8 -/- colonocyte mitochondria in vivo are smaller and rounder and that mitochondrial motility is increased in K8 -/- Caco-2 cells. Furthermore, K8 -/- Caco-2 cells displayed diminished mitochondrial respiration and decreased mitochondrial membrane potential compared with controls, whereas glycolysis was not affected. The levels of mitochondrial respiratory chain complex proteins and mitochondrial regulatory proteins mitofusin-2 and prohibitin were decreased both in vitro in K8 -/- Caco-2 cells and in vivo in K8 -/- mouse colonocytes, and reexpression of K8 into K8 -/- Caco-2 cells normalizes the mitofusin-2 levels. Mitochondrial Ca 2+ is an important regulator of mitochondrial energy metabolism and homeostasis, and Caco-2 cells lacking K8 displayed decreased levels and altered dynamics of mitochondrial matrix and cytoplasmic Ca 2+ . In summary, these novel findings attribute an important role for colonocyte K8 in stabilizing mitochondrial shape and movement and maintaining mitochondrial respiration and Ca 2+ signaling. Further, how these metabolically compromised colonocytes are capable of hyperproliferating presents an intriguing question for future studies. NEW & NOTEWORTHY In this study, we show that colonocyte intermediate filament protein keratin 8 is important for stabilizing mitochondria and maintaining mitochondrial energy metabolism, as keratin 8-deficient colonocytes display smaller, rounder, and more motile mitochondria, diminished mitochondrial respiration, and altered Ca 2+ dynamics. Changes in fusion-regulating proteins are rescued with reexpression of keratin 8. These alterations in colonocyte mitochondrial homeostasis contribute to keratin 8-associated colitis pathophysiology.

The relationship between the mechanical forces associated with bowel movement and colonic mucosal physiology is understudied. This is partly due to the limited availability of physiologically relevant fecal models that can exert these mechanical stimuli in in vitro colon models in a simple-to-implement manner. In this report, we created a mucus-coated fecal surrogate that was magnetically propelled to produce a controllable sweeping mechanical stimulation on primary intestinal epithelial cell monolayers. The mucus layer was derived from purified porcine stomach mucins, which were first modified with reactive vinyl sulfone (VS) groups followed by reaction with a thiol crosslinker (PEG-4SH) via a Michael addition click reaction. Formation of mucus hydrogel network was achieved at the optimal mixing ratio at 2.5 % w/v mucin-VS and 0.5 % w/v PEG-4SH. The artificial mucus layer possessed similar properties as the native mucus in terms of its storage modulus (66 Pa) and barrier function (resistance to penetration by 1-μm microbeads). This soft, but mechanically resilient mucus layer was covalently linked to a stiff fecal hydrogel surrogate (based on agarose and magnetic particles, with a storage modulus of 4600 Pa). The covalent bonding between the mucus and agarose ensured its stability in the subsequent fecal sliding movement when tested at travel distances as long as 203 m. The mucus layer served as a lubricant and protected epithelial cells from the moving fecal surrogate over a 1 h time without cell damage. To demonstrate its utility, this mucus-coated fecal surrogate was used to mechanically stimulate a fully differentiated, in vitro primary colon epithelium, and the physiological stimulated response of mucin-2 (MUC2), interleukin-8 (IL-8) and serotonin (5HT) secretion was quantified. Compared with a static control, mechanical stimulation caused a significant increase in MUC2 secretion into luminal compartment (6.4 × ), a small but significant increase in IL-8 secretion (2.5 × and 3.5 × , at both luminal and basal compartments, respectively), and no detectable alteration in 5HT secretion. This mucus-coated fecal surrogate is expected to be useful in in vitro colon organ-on-chips and microphysiological systems to facilitate the investigation of feces-induced mechanical stimulation on intestinal physiology and pathology., Competing Interests: Declaration of competing interest Y.W., C.E.S., and N.L.A. have a financial interest in Altis Biosystems, Inc. A.S.W and C.V.-N. declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fat and sugar overconsumption is the cause of increasing worldwide incidence of gastrointestinal tract in inflammatory conditions. The intestinal pre-inflammatory alterations are partially reversible, simultaneously inhibiting the predisposition to colitis. Searching for an effective pharmacotherapy for treating inflammatory conditions in the intestine is essential. This study aimed to investigate the effect of cannabigerol (CBG) on the inflammation state in the colon tissue of rats subjected to high-caloric diet. The experiment was conducted on male Wistar rats subjected to a standard or a high-fat high-sucrose diets for six weeks. For the last 14 days, half of rats from both groups received intragastrically cannabigerol solution (30 mg/kg of body mass). The ratio of n-6/n-3 PUFA, the activity of n-6 and n-3 PUFA, and arachidonic acid (AA) content in selected lipid fractions were determined by gas-liquid chromatography. Immunoblotting examined the expression of proteins involved in inflammation development. ELISA kits measured the content of arachidonic acid derivatives. CBG treatment reduced the n-6/n-3 PUFA ratio in TAG fraction and increased the n-3 PUFA pathway activity in almost all lipid fractions. Cannabigerol supplementation decreased AA concentration in PL and TAG. CBG also caused diminishments in the expression of cPLA 2 , COX-1, COX-2, and 12/15-LOX, which was indirectly correlated with a decreased LTB4 level and an increased LXA4 level. We concluded that cannabigerol has a protective influence on the development of inflammation in the colon tissue under lipid and sugar overload condition, thereby favoring cancer initiation and progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

New derivatives of tropane scaffold were prepared from the reaction of their thione or thioamide derivatives with α-halocarbonyl compounds. The structures of all new derivatives were assured and proved with their spectral data. The novel tropane derivatives were examined for their cytotoxicity on two colon tumor cell lines; Caco2 and HCT116 cells. The most active compounds 3, 4, 5, 9d and 14a displayed significant antitumor activities with IC 50 range of 9.50 - 30.15 μM compared to doxorubicin. Moreover, they revealed reduced cytotoxic effect on WI-38 normal ones, signifying their great safety. With the aim of better understanding the inhibitory potential of such compounds on heat-shock protein 90 (Hsp90), there activities were assessed against such enzyme demonstrating high inhibitory activities with IC 50 range of 56.58-78.85 nM. Western blotting was carried out to ensure the inhibitory activity on Hsp90, results showed that 3 markedly suppressed Hsp90 expression on Caco2 cell line. Additionally, a molecular docking analysis of the most potent derivatives at the Hsp90 binding site was carried out in order to approve the performed in vitro assays., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Colorectal clear cell adenocarcinomas are rare tumors. They can be divided into two types: intestinal- and Müllerian-type. Most intestinal-type clear cell adenocarcinomas show a composite morphology, and most early-stage (T1) intestinal-type clear cell adenocarcinomas have an adenoma component. We report an additional early-stage (T1) colonic clear cell adenocarcinoma that was a de novo adenocarcinoma without any adenoma component. It had a pure morphology and the smallest size (0.6 cm) ever reported. Immunohistochemical results demonstrated an intestinal phenotype (KRT20+, KRT7-, CEA+, and CDX2+). Periodic acid-schiff and alcian blue stains were both negative, which demonstrated decrease in mucin expression in the clear tumor cells. Enteroblastic differentiation was observed in a few colorectal clear cell adenocarcinomas in the literature, while it had not been observed in the present tumor. The tumor did not have deep submucosal invasion and cancer embolus, endoscopic submucosal dissection with regular follow-up was an appropriate treatment for the patient. Due to the rarity and diversity of primary colorectal clear cell adenocarcinomas, the cause of clear cytoplasm change and the impact on patient prognosis remain unknown. Accumulating evidence indicates that clear cell adenocarcinomas of intestinal-type is a histological variant of colorectal adenocarcinoma., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic abdominal pain in the absence of ongoing disease is the hallmark of disorders of gut-brain interaction (DGBIs), including irritable bowel syndrome (IBS). While the etiology of DGBIs remains poorly understood, there is evidence that both genetic and environmental factors play a role. In this study, we report the identification and validation of arginine-vasopressin receptor 1A (Avpr1a) as a novel candidate gene for visceral hypersensitivity (VH), a primary peripheral mechanism underlying abdominal pain in DGBI/IBS. Comparing 2 C57BL/6 (BL/6) substrains (C57BL/6NTac and C57BL/6J) revealed differential susceptibility to the development of chronic VH following intrarectal zymosan instillation, a validated preclinical model for postinflammatory IBS. Using whole-genome sequencing, we identified a single-nucleotide polymorphism differentiating the 2 strains in the 5' intergenic region upstream of Avpr1a, encoding the protein Avpr1a. We used behavioral, histological, and molecular approaches to identify distal colon-specific gene expression and neuronal hyperresponsiveness covarying with Avpr1a genotype and VH susceptibility. While the 2 BL/6 substrains did not differ across other gastrointestinal phenotypes (eg, fecal water retention), VH-susceptible BL/6NTac mice had higher colonic Avpr1a mRNA and protein expression. These results parallel findings that patients' colonic Avpr1a mRNA expression corresponded to higher pain ratings. Moreover, neurons of the enteric nervous system were hyperresponsive to the Avpr1a agonist arginine-vasopressin, suggesting a role for enteric neurons in the pathology underlying VH. Taken together, these findings implicate differential regulation of Avpr1a as a novel mechanism of VH susceptibility as well as a potential therapeutic target specific to VH. PERSPECTIVE: This article presents evidence of Avpr1a as a novel candidate gene for VH in a mouse model of IBS. Avpr1a genotype and/or tissue-specific expression represents a potential biomarker for chronic abdominal pain susceptibility., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Invasive fungal intestinal infections are rare in pediatric patients with limited studies reported to date., Methods: Retrospective study of invasive intestinal fungal infections in pediatric patients. For fungal specification, 18S rRNA gene PCR was performed using formalin-fixed paraffin-embedded tissues., Results: A total of 19 cases from 18 patients were included (13 males, 72%) with a median age of 20 days (8 days-14 years). About 13 patients (72%) presented within 67 days of birth and 11 patients (61%) were premature and 14 patients (78%) had a significant medical history. The most common location was the jejunum/ileum (56%) followed by the right colon and terminal ileum (22%). In 10 patients, the fungal elements were seen in the mucosa with 3 extending into the submucosa, and only 3 patients showed full-thickness involvement. Tissue necrosis and angioinvasion were seen in 13 (72%) and 8 (44%) patients, respectively. Morphologically, organisms consistent with Candida spp. were seen in 17 patients and with a mucoraceous mold in 1 patient. A 18S rRNA gene sequencing performed in 18 cases identified Candida dubliniensis in 16 cases and Candida spp. in 2 cases. During the study follow-up period, 56% of the patients died., Conclusion: In our experience, most cases were due to Candida spp. and predominantly in premature infants and associated with poor outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A bridge to surgery (BTS) after self-expandable metallic stent (SEMS) placement is a widely recognized treatment strategy for obstructive colorectal cancer. However, there is still a lack of evidence for the efficacy and safety of laparoscopic surgery following SEMS placement. The aim of this systematic review and meta-analysis was to compare the short-term and long-term outcomes of laparoscopic surgery with those of open surgery following SEMS placement in patients with obstructive colorectal cancer., Methods: An electronic literature search through to December 2022 was performed to identify studies comparing short-term and long-term outcomes between laparoscopic and open surgery following SEMS placement for obstructive colorectal cancer. The main outcome measures were postoperative complication rates and mortality. Secondary outcome measures were the 3-year recurrence-free survival (RFS) and 3-year overall survival (OS) rates. The meta-analysis was performed using fixed-effect or random-effects methods to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs)., Results: The meta-analysis included 15 studies and 883 patients, of whom 467 (52.9%) underwent laparoscopic surgery and 416 (47.1%) underwent open surgery following SEMS placement. The postoperative complication rate was significantly lower in the laparoscopic surgery group than in the open surgery group (OR 0.47, 95% CI 0.32-0.67, P < 0.001). There was no significant difference in the 3-year RFS rate or 3-year OS rate between the laparoscopic and open surgery groups (3-year RFS, OR 0.78, 95% CI 0.50-1.24, P = 0.30; 3-year OS, OR 0.68, 95% CI 0.41-1.12, P = 0.13)., Conclusion: This meta-analysis found that the short-term outcome was better in patients who underwent laparoscopic surgery following SEMS placement than in those who underwent open surgery. Furthermore, there was no significant difference in long-term outcomes between the two groups. Laparoscopic surgery following SEMS placement may be a safe and effective treatment option for obstructive colorectal cancer., (© 2024. The Author(s).)

Elastrofibromas are rare lesions characterized by collagen and elastic fiber deposition. They are generally found in soft tissues and throughout the gastrointestinal tract. The pathogenesis of this lesion is still uncertain, but it is hypothesized to be a reactive process. We present a case of an appendiceal elastofibroma, a unique anatomic location that necessitated surgical removal, with pathologic findings suggestive of an inciting event from a sclerosed vascular abnormality., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Previously, many studies have reported changes in the gut microbiota of patients with colorectal cancer (CRC). While CRC is a well-described disease, the relationship between its development and features of the intestinal microbiome are still becoming understood. Evidence linking Fusobacterium nucleatum enrichment in colorectal tumor tissue has prompted the elucidation of various molecular mechanisms and tumor-promoting attributes. In this review we highlight various aspects of our understanding of the relationship between the development of CRC and the alteration of intestinal microbiome, focusing specifically on the role of F. nucleatum. As the amount of F. nucleatum DNA in CRC tissue is associated with shorter survival, it may potentially serve as a prognostic biomarker, and most importantly may open the door for a role in CRC treatment.

Endometriosis, characterized by the ectopic implantation of endometrial tissue, typically involves pelvic structures but infrequently extends to extrapelvic sites such as the gastrointestinal tract. In this report, we present a case of a 44-year-old woman with diffuse abdominal discomfort and constipation. Computed tomography imaging revealed a mass in the cecum, leading to diagnostic colonoscopy and subsequent magnetic resonance imaging. Ultimately, laparoscopy revealed a puckered cecal mass suspected to be invasive malignancy but pathologically confirmed as extensive endometriosis involving the colonic wall and pericolic lymph nodes. Cecal volvulus secondary to endometriosis is exceedingly rare, with surgical intervention being the primary treatment modality. Endometriosis-associated gastrointestinal involvement often masquerades as irritable bowel syndrome, highlighting the importance of considering atypical presentations in young women. This case underscores the need to maintain a high index of suspicion for unusual etiologies in patients with gastrointestinal symptoms and atypical imaging findings to facilitate timely diagnosis and management., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

This study addresses the gap in translatable in vitro models for investigating Enterohemorrhagic E. coli (EHEC) infections, particularly relevant to both canine and human health. EHEC is known to induce acute colitis in dogs, leading to symptoms like hemorrhagic diarrhea and hemolytic uremic syndrome, similar to those observed in humans. However, understanding the pathophysiology and developing treatment strategies have been challenging due to the lack of effective models that replicate the clinical disease caused by EHEC in both species. Our approach involved the development of colonoid-derived monolayers using intestinal tissues from healthy, client-owned dogs. These monolayers were exposed to EHEC, and the impact of EHEC was assessed through several techniques, including trans-epithelial electrical resistance (TEER) measurement, immunofluorescence staining for junction proteins and mucus, and scanning electron microscopy for morphological analysis. Modified culture with saline, which was intended to prevent bacterial overgrowth, maintained barrier integrity and cell differentiation. EHEC infection led to significant decreases in TEER and ZO-1 expression, but not in E-cadherin levels or mucus production. In addition, EHEC elicited a notable increase in tumor necrosis factor-alpha production, highlighting its distinct impact on canine intestinal epithelial cells compared to non-pathogenic E. coli . These findings closely replicate in vivo observations in dogs and humans with EHEC enteropathy, validating the canine colonoid-derived monolayer system as a translational model to study host-pathogen interactions in EHEC and potentially other clinically significant enteric pathogens., Importance: This study develops a new model to better understand Enterohemorrhagic E. coli (EHEC) infections, a serious bacterial disease affecting both dogs and humans, characterized by symptoms such as hemorrhagic diarrhea and hemolytic uremic syndrome. Traditional research models have fallen short of mimicking how this disease manifests in patients. Our research used intestinal tissues from healthy dogs to create layers of cells, known as colonoid-derived monolayers, which we then exposed to EHEC. We assessed the damage caused by the bacteria using several techniques, observing significant changes similar to those seen in actual cases of the disease. The model proved effective in replicating the interaction between the host and the pathogen, marking an important step toward understanding EHEC's effects and developing treatments. This canine colonoid-derived monolayer system not only bridges a crucial gap in current research but also offers a promising platform for studying other enteric pathogens affecting both canine and human health.

Background: Schistosomiasis, officially named as a neglected tropical disease by The World Health Organization, is a serious parasitic disease caused by trematode flukes of the genus Schistosoma . It is a common infectious disease, endemic in more than 78 countries. The disease can involve various organs and poses far-reaching public health challenges., Case Summary: Here, we present a series of five patients with variable presentations: an asymptomatic patient who was diagnosed with colonic schistosomiasis upon screening colonoscopy; 2 patients with clinical suspicion of colonic cancer; and 2 patients with a clinical diagnosis of inflammatory bowel disease. All patients were subsequently confirmed to have colonic schistosomiasis after colonoscopy and histopathologic examination. The clinical manifestations, colonoscopy features and histologic findings of the patients are described. Most of the patients showed significant clinical improvement following administration of oral praziquantel., Conclusion: Intestinal schistosomiasis can present with features mimicking other gastrointestinal conditions. This disease should be a diagnostic consideration in patients who live in or have traveled to endemic areas., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Wireless activation of the enteric nervous system (ENS) in freely moving animals with implantable optogenetic devices offers a unique and exciting opportunity to selectively control gastrointestinal (GI) transit in vivo, including the gut-brain axis. Programmed delivery of light to targeted locations in the GI-tract, however, poses many challenges not encountered within the central nervous system (CNS). We report here the development of a fully implantable, battery-free wireless device specifically designed for optogenetic control of the GI-tract, capable of generating sufficient light over large areas to robustly activate the ENS, potently inducing colonic motility ex vivo and increased propulsion in vivo. Use in in vivo studies reveals unique stimulation patterns that increase expulsion of colonic content, likely mediated in part by activation of an extrinsic brain-gut motor pathway, via pelvic nerves. This technology overcomes major limitations of conventional wireless optogenetic hardware designed for the CNS, providing targeted control of specific neurochemical classes of neurons in the ENS and brain-gut axis, for direct modulation of GI-transit and associated behaviours in freely moving animals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nick J. Spencer reports financial support was provided by National Health and Medical Research Council (NHMRC). Nick J. Spencer reports financial support was provided by Australian Research Council (ARC) Discovery Project. Abraham Vázquez-Guardado reports financial support was provided by NC State University. John A. Rogers reports financial support was provided by Northwestern University Querrey Simpson Institute for Bioelectronics. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Propolis exhibits significant anti-inflammatory, antidiabetic, and antiobesity properties in both mouse models and clinical applications. However, the underlying metabolic mechanisms remain poorly understood. Traditional metabolomic methods that rely on chromatographic separation require complex preprocessing steps and extended detection periods. In this study, we employed extraction electrospray ionization mass spectrometry combined with multivariate analysis to directly profile metabolites in the colon tissue of mice. Our findings demonstrate the efficacy of ethanol extract of propolis (EEP) in mitigating weight gain, reducing inflammatory cytokines, and improving insulin resistance induced by a high-fat diet. Additionally, EEP enhanced glucose tolerance. Through collision-induced dissociation experiments, we identified 26 metabolites, with 4-hydroxyphenylacetic acid, protocatechuic acid, caffeic acid, ferulic acid, hippuric acid, histidine, and tryptophan emerging as potential biomarkers. Notably, tryptophan exhibited the highest content at 8.25 mg/g. Our research facilitates rapid profiling of colon metabolites, underscoring its significant potential for broader applications in animal metabolomic studies.

Objective: Hirschsprung disease (HSCR) is a severe congenital disorder affecting 1:5000 live births. HSCR results from the failure of enteric nervous system (ENS) progenitors to fully colonise the gastrointestinal tract during embryonic development. This leads to aganglionosis in the distal bowel, resulting in disrupted motor activity and impaired peristalsis. Currently, the only viable treatment option is surgical resection of the aganglionic bowel. However, patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often necessary. Hence, alternative treatment options are crucial. An attractive strategy involves the transplantation of ENS progenitors generated from human pluripotent stem cells (hPSCs)., Design: ENS progenitors were generated from hPSCs using an accelerated protocol and characterised, in detail, through a combination of single-cell RNA sequencing, protein expression analysis and calcium imaging. We tested ENS progenitors' capacity to integrate and affect functional responses in HSCR colon, after ex vivo transplantation to organotypically cultured patient-derived colonic tissue, using organ bath contractility., Results: We found that our protocol consistently gives rise to high yields of a cell population exhibiting transcriptional and functional hallmarks of early ENS progenitors. Following transplantation, hPSC-derived ENS progenitors integrate, migrate and form neurons/glia within explanted human HSCR colon samples. Importantly, the transplanted HSCR tissue displayed significantly increased basal contractile activity and increased responses to electrical stimulation compared with control tissue., Conclusion: Our findings demonstrate, for the first time, the potential of hPSC-derived ENS progenitors to repopulate and increase functional responses in human HSCR patient colonic tissue., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Problem: There is a higher incidence of irritable bowel syndrome with miscarriages, and recurrent miscarriages of otherwise normal embryos have been linked to subnormal expression of the immune checkpoint inhibitor CD200L. We sought to determine if alterations in the expression of the CD200 immune checkpoint inhibitor occur in colonic tissue in IBS-D patients., Method of Study: Quantitative immunohistochemical staining of biopsies from proximal and distal colon or rectum for the inhibitory CD200L and CD200S molecules was done. CD56 cells were also enumerated as they play a role in recurrent miscarriages and may express CD200S., Results: CD200L was decreased and CD200S was unchanged in epithelium but not stroma of 3 IBS-D cases. One case had an increase in both CD200L and CD200S. CD56 cells were also stained for CD200S. Degranulation was assessed by the percentage of extracellular CD200S that was increased as epithelial CD200L decreased., Conclusions: This pilot study was promising and warrants a larger sample to determine if a correlation between uterine implantation site CD200L and CD200S expression in normal and failing implantation sites is needed. Colonic epithelial CD200L may then provide useful information about the pathogenesis of the spontaneous miscarriage in individual cases., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

After birth, the development of secondary lymphoid tissues (SLTs) in the colon is dependent on the expression of the aryl hydrocarbon receptor (AhR) in immune cells as a response to the availability of AhR ligands. However, little is known about how AhR activity from intestinal epithelial cells (IECs) may influence the development of tertiary lymphoid tissues (TLTs). As organized structures that develop at sites of inflammation or infection during adulthood, TLTs serve as localized centers of adaptive immune responses, and their presence has been associated with the resolution of inflammation and tumorigenesis in the colon. Here, we investigated the effect of the conditional loss of AhR activity in IECs in the formation and immune cell composition of TLTs in a model of acute inflammation. In females, loss of AhR activity in IECs reduced the formation of TLTs without significantly changing disease outcomes or immune cell composition within TLTs. In males lacking AhR expression in IECs, increased disease activity index, lower expression of functional-IEC genes, increased number of TLTs, increased T-cell density, and lower B- to T-cell ratio were observed. These findings may represent an unfavorable prognosis when exposed to dextran sodium sulfate (DSS)-induced epithelial damage compared with females. Sex and loss of IEC AhR also resulted in changes in microbial populations in the gut. Collectively, these data suggest that the formation of TLTs in the colon is influenced by sex and AhR expression in IECs. NEW & NOTEWORTHY This is the first research of its kind to demonstrate a clear connection between biological sex and the development of tertiary lymphoid tissues (TLT) in the colon. In addition, the research finds that in a preclinical model of inflammatory bowel disease, the expression of the aryl hydrocarbon receptor (AhR) influences the development of these structures in a sex-specific manner.

Purpose: We investigated the current practices and perceptions of colorectal surgeons in South Korea regarding intracorporeal ileocolic anastomosis (IIA) in minimally invasive right hemicolectomy (RHC)., Methods: Members of the Korean Society of Coloproctology (KSCP) participated in an online survey encompassing demographic information, surgical experiences, methods for IIA, and advantages, barriers, and perceptions of IIA. We performed a statistical analysis of survey results., Results: Among the 1,074 KSCP members contacted, 178 responded to the survey. Most respondents were males aged 40-49 years with >10 years of experience who were affiliated with a tertiary healthcare facility. One hundred fifty-six respondents had performed <100 colorectal cancer surgeries annually. Fifty-nine respondents reported experiences of the IIA technique in minimally invasive RHC. Most respondents favored the isoperistaltic side-to-side (S-S) anastomosis and stapled S-S anastomosis, hand-sewn closure for the common channel, and the periumbilical area for primary specimen extraction. Respondents with IIA experience emphasized the reduction in postoperative complications as the primary reason for performing IIA, whereas respondents without IIA experience cited the lack of benefits as the main deterrent. Respondents commonly cited concerns regarding anastomotic leakage and intraabdominal contamination as the primary reasons for not performing IIA. Respondents with IIA experience demonstrated a more positive response towards attempting or transitioning to IIA than those without. Respondents with IIA experience prioritized self-sufficiency, whereas respondents without IIA experience prioritized proctorship and discussions of the initial cases., Conclusion: Measures to standardize the IIA technique and appropriate training programs must be implemented to enhance its use in minimally invasive RHC., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Alcohol use disorder accounts for a growing worldwide health system concern. Alcohol causes damages to various organs, including intestine and liver, primarily involved in its absorption and metabolism. However, alcohol-related organ damage risk varies significantly among individuals, even when they report consuming comparable dosages of alcohol. Factor(s) that may modulate the risk of organ injuries from alcohol consumption could be responsible for inter-individual variations in susceptibility to alcohol-related organ damages. Accumulating evidence suggests disruptions in circadian rhythm can exacerbate alcohol-related organ damages. Here we investigated the interplay between alcohol, circadian rhythm, and key tissue cellular processes at baseline, after a regular and a shift in the light/dark cycle (LCD) in mice. Central/peripheral clock expression of core clock genes (CoClGs) was analyzed. We also studied circadian homeostasis of tissue cellular processes that are involved in damages from alcohol. These experiments reveal that alcohol affects the expression of CoClGs causing a central-peripheral dyssynchrony, amplified by shift in LCD. The observed circadian clock dyssynchrony was linked to circadian disorganization of key processes involved in the alcohol-related damages, particularly when alcohol was combined with LCD. These results offer insights into the mechanisms by which alcohol interacts with circadian rhythm disruption to promote organ injury., (© 2024 Wiley‐VCH GmbH.)

Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called "mini-colons." By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated in vivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment., Competing Interests: Declaration of interests The Ecole Polytechnique Fédérale de Lausanne has filed for patent protection on the technology described herein, and M.N. and M.P.L. are named as inventors on those patents; M.P.L. is a shareholder in Doppl SA, which is commercializing those patents. All authors, except for N.B., are employees of Hoffmann-La Roche., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The intestinal epithelium is covered by mucus that protects the tissue from the luminal content. Studies have shown that anion secretion via the cystic fibrosis conductance regulator (Cftr) regulates mucus formation in the small intestine. However, mechanisms regulating mucus formation in the colon are less understood. The aim of this study was to explore the role of anion transport in the regulation of mucus formation during steady state and in response to carbamylcholine (CCh) and prostaglandin E 2 (PGE 2 ). The broad-spectrum anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), CftrdF508 (CF) mice, and the slc26a3 inhibitor SLC26A3-IN-2 were used to inhibit anion transport. In the distal colon, steady-state mucus expansion was reduced by SLC26A3-IN-2 and normal in CF mice. PGE 2 stimulated mucus expansion without de novo mucus release in wild type (WT) and CF colon via slc26a3 sensitive mechanisms, while CCh induced de novo mucus secretion in WT but not in CF colon. However, when added simultaneously, CCh and PGE 2 stimulated de novo mucus secretion in the CF colon via DIDS-sensitive pathways. A similar response was observed in CF ileum that responded to CCh and PGE 2 with DIDS-sensitive de novo mucus secretion. In conclusion, this study suggests that slc26a3 regulates colonic mucus expansion, while Cftr regulates CCh-induced de novo mucus secretion from ileal and distal colon crypts. Furthermore, these findings demonstrate that in the absence of a functional Cftr channel, parallel stimulation with CCh and PGE 2 activates additional anion transport processes that help release mucus from intestinal goblet cells., (© 2024. The Author(s).)

Background: A multitude of mouse models are utilized to emulate and study intestinal inflammation. T-cell receptor alpha chain (TCRα)-deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis. However, colitis is triggered late in the life of the mouse (age: 4-5 months), and inflammation does not develop at the same time in different mice. A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα-deficient mice at the age of 6-8 weeks. However, a detailed characterization of ensuing inflammation was not provided., Methods: We conducted an in-depth examination of piroxicam-triggered colitis in TCRα-deficient mice, with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers. Furthermore, we tested amelioration of colitis with dexamethasone., Results: We confirmed that piroxicam induced a time-prescribed colitis and did so in the proximal colon as well as the cecum of TCRα-deficient mice. Piroxicam administration was observed to induce epithelial hyperplasia, goblet cell loss, and leukocyte infiltration with occasional ulceration. A Swiss roll technique was used to examine the colon and cecum in its entirety. Importantly, we observed that inflammation was multifocal segmental, with areas of tissue damage in between healthy tissue. In addition, we observed variability in the severity of inflammation among replicate animals and treatments, and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon., Conclusions: Piroxicam consistently induced multifocal segmental colitis in the proximal colon and cecum, although the degree of inflammation was reduced in the latter. Importantly, spatial variability in inflammation in the large intestine and the inter-replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis., (© 2024 His Majesty the King in Right of Canada and The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences. Reproduced with the permission of the Minister of Agriculture and Agri Food Canada.)

Inflammatory bowel disease (IBD) is a morbid condition characterized by relapsing-remitting inflammation of the colon, accompanied by persistent gut dysmotility and abdominal pain. Different reports demonstrated biological activities of aged black garlic (ABG), including anti-inflammatory and antioxidant effects. We aimed to investigate beneficial effects exerted by ABGE on colon inflammation by using ex vivo and in vivo experimental models. We investigated the anti-inflammatory effects of an ABG water extract (ABGE) on rat colon specimens exposed to E. coli lipopolysaccharide (LPS), a known ex vivo experimental model of ulcerative colitis. We determined gene expression of various biomarkers involved in inflammation, including interleukin (IL)-1β, IL-6, nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α. Moreover, we studied the acute effects of ABGE on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) injection in rats. ABGE suppressed LPS-induced gene expression of IL-1β, IL-6, NF-kB, and TNF-α. In addition, the acute administration of ABGE (0.03-1 g kg -1 ) dose-dependently relieved post-inflammatory visceral pain, with the higher dose (1 g kg -1 ) able to significantly reduce both the behavioral nociceptive response and the entity of abdominal contraction (assessed by electromyography) in response to colorectal distension after the acute administration in DNBS-treated rats. Present findings showed that ABGE could represent a potential strategy for treatment of colitis-associated inflammatory process and visceral pain. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin., (© 2024 John Wiley & Sons Ltd.)

Background: Endoscopic sub-mucosal dissection (ESD) is an established endoscopic modality for the management of colorectal polyps. However, there are no studies regarding the outcomes of ESD from India. In this study, we aimed at evaluating the outcomes of ESD in patients with adenomatous polyps in the colon and rectum., Methods: Data of consecutive patients who underwent ESD for colorectal polyps from 2018 to 2021 were analyzed, retrospectively. The primary outcome of the study was the technical success of ESD. The secondary outcomes included the rate of histologically complete resection (R0), adverse events and recurrence., Results: Seventy patients (63.5 years, 60% males) underwent ESD for polyps in colon and rectum. A majority were located in rectum (80%) and sigmoid colon (15.7%). Narrow band classification of the polyps was Japanese Narrow Band Imaging Expert Team (JNET)-2a in 50 (71.4%) and JNET-2b in 13 (18.6%) patients. ESD was technically successful in 64 (91.4%) patients using conventional technique (72.8%) and pocket or tunnelling technique (18.6%). There were no major adverse events. Histologically RO was achieved in 58 (82.8%) patients and deep sub-mucosal invasion was noted in 12 patients. At a median follow-up of 19 (interquartile range [IQR] 15-27) months, recurrence was noticed in four (5.7%) patients all of which could be managed endoscopically., Conclusion: ESD, performed at a tertiary care centre in India, yields high rates of technical success and histologically R0, with a relatively low incidence of adverse events and recurrences., (© 2024. Indian Society of Gastroenterology.)

A 66-year-old woman with rheumatoid arthritis (RA) who had been receiving methotrexate (MTX) for 2 years presented with tarry stools. Contrast-enhanced computed tomography (CT) of the abdomen revealed irregular wall thickening in the ileocecal region and multiple low-contrast masses in both lobes of the liver. Lower gastrointestinal endoscopy revealed a type 2 tumor in the ileocecal region with a semi-peripheral ulcer. Histological examination of liver and colon biopsies showed other iatrogenic immunodeficiency-associated lymphoproliferative disorder (Oi-LPD), diffuse large B-cell lymphoma type, with positivity for Epstein-Barr virus DNA. After withdrawal of MTX, the LPD lesions disappeared and the patient achieved remission. We considered this to be a sporadic case of Oi-LPD, diffuse large B-cell lymphoma type, in the liver and colon due to treatment with MTX. There has been no previous report of this condition with simultaneous hepatic and colonic lesions, and the present case is thought to be highly informative in relation to the pathogenesis., (© 2024. The Author(s).)

Background: Mobile phone-based SMS text message reminders have the potential to improve colorectal cancer screening participation rates., Objective: This study assessed the effectiveness and acceptability of adding targeted SMS text message reminders to the standard procedure for those who picked up but did not return their screening kit at the pharmacy within 14 days in a colorectal cancer screening program in Catalonia, Spain., Methods: We performed a randomized control trial among individuals who picked up a fecal immunochemical test (FIT) kit for colorectal cancer screening at the pharmacy but did not return it within 14 days. The intervention group (n=4563) received an SMS text message reminder on the 14th day of kit pick up and the control group (n=4806) received no reminder. A 30-day reminder letter was sent to both groups if necessary. The main primary outcome was the FIT completion rate within 30, 60, and 126 days from FIT kit pick up (intention-to-treat analysis). A telephone survey assessed the acceptability and appropriateness of the intervention. The cost-effectiveness of adding an SMS text message reminder to FIT completion was also performed., Results: The intervention group had higher FIT completion rates than the control group at 30 (64.2% vs 53.7%; P<.001), 60 (78.6% vs 72.0%; P<.001), and 126 (82.6% vs 77.7%; P<.001) days. Participation rates were higher in the intervention arm independent of sex, age, socioeconomic level, and previous screening behavior. A total of 339 (89.2%) interviewees considered it important and useful to receive SMS text message reminders for FIT completion and 355 (93.4%) preferred SMS text messages to postal letters. We observed a reduction of US $2.4 per participant gained in the intervention arm for invitation costs compared to the control arm., Conclusions: Adding an SMS text message reminder to the standard procedure significantly increased FIT kit return rates and was a cost-effective strategy. SMS text messages also proved to be an acceptable and appropriate communication channel for cancer screening programs., Trial Registration: ClinicalTrials.gov NCT04343950; https://www.clinicaltrials.gov/study/NCT04343950., International Registered Report Identifier (irrid): RR2-10.1371/journal.pone.0245806., (©Nuria Vives, Noemie Travier, Albert Farre, Gemma Binefa, Carmen Vidal, Maria Jose Pérez Lacasta, Gemma Ibáñez-Sanz, Ena Pery Niño de Guzmán, Jon Aritz Panera, Montse Garcia, M-TICS Research Group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.07.2024.)

Introduction: Immunoglobulin G (IgG) is important in mediating humoral immunity and in the maintenance of immune homeostasis in the intestinal mucosa. Oregano essential oil (OEO) is a natural herbal extract that possesses antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. As the effects of OEO on intestinal mucosal immunity in Holstein dairy bulls remained unclear, we investigated the effect of dietary supplementation of OEO on IgG levels and IgG + cells residing in the intestinal tract in Holstein dairy bulls., Methods: Twelve Holstein bulls in good health of approximately 10 months of age were selected for the experiment and randomly equally divided into two groups. The control (CK) group was fed a basal ration, and in the OEO group, the basal ration was supplemented with OEO (20 g/head/day). After 300 days of feeding, tissue samples of the jejunum, ileum, and colon of the bulls in each group were collected for histopathological analysis, immunohistochemistry, and enzyme-linked immunosorbent assays, respectively., Results: The jejunum, ileum, and colon of bulls in the CK group had obvious pathological damage, whereas the structure of each intestinal segment was clear and intact. In the OEO group, pathological damage was significantly reduced. IgG + plasma cells were diffusely distributed in the lamina propria of the jejunum, ileum, and colon in the CK and OEO groups, with no significant difference between the groups. OEO supplementation significantly reduced the number of IgG+ plasma cells in each intestinal segment, with the highest decrease rate being noted for the ileum (22.87%), followed by the colon (19.45%) and jejunum (8.52%). ELISA test results and immunohistochemical results were mutually verified. The change in IgG content was consistent with the trend of change in the number of IgG + plasma cells., Discussion: Our findings suggest that OEO supplementation does not alter the diffuse spatial distribution of IgG + plasma cells in the intestines of Holstein dairy bulls, but lowers immunoglobulin levels to normal levels, significantly reduces intestinal damage, and may enhance mucosal immune defence barrier function by inhibiting inflammatory reactions., Competing Interests: QC was employed by Jing Chuan Xu Kang Food Co., Ltd. ZZ was employed by Gansu Huarui Agriculture Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Zhang, Kong, Wang, Pan, Shi, Liu, He, Ma, Cheng, Zhang and Lei.)

The aim of this study is to compare the diagnostic performance of magnetic resonance imaging (MRI) against computed tomography (CT) in various aspects of local staging in colon cancer patients. This study was a prospective single arm diagnostic accuracy study. All consecutive adult patients with confirmed colon cancer that met the current criteria for surgical resection were considered as eligible. Diagnostic performance assessment included T (T1/T2 vs T3/T4 and < T3ab vs > T3cd) and N (N positive) staging, serosa and retroperitoneal surgical margin (RSM) involvement and extramural vascular invasion (EMVI). Imaging was based on a 3 Tesla MRI system and the evaluation of all sequences (T1, T2 and diffusion-weighted imaging-DWI series) by two independent readers. CT scan was performed in a 128 row multidetector (MD) CT scanner (slice thickness: 1 mm) with intravenous contrast. Pathology report was considered as the gold standard for local staging. Sensitivity (SE), specificity (SP), and area under the curve (AUC) were calculated for both observers. MRI displayed a higher diagnostic performance over CT in terms of T1/T2 vs T3/T4 (SE: 100% vs 83.9%, SP: 96.6% vs 81%, AUC: 0.825 vs 0.983, p < 0.001), N positive (p < 0.001) and EMVI (p = 0.023) assessment. An excellent performance of MRI was noted in the T3ab vs T3cd (CT AUC Reader1 : 0.636, AUC Reader2 : 0.55 vs MRI AUC Reader1 : 0.829 AUC Reader2 0.846, p = 0.01) and RSM invasion diagnosis. In contrast to these, MRI did not perform well in the identification of serosa invasion. MRI had a higher diagnostic yield than CT in several local staging parameters., (© 2024. The Author(s).)

Spinal pneumorrhachis is a relatively rare condition. Herein, we describe a case of whole spinal pneumorrhachis. A 68-year-old male, with a history of total proctocolectomy due to ulcerative colitis, had fever, diarrhea, and inflammatory reactions. Computed tomography (CT) revealed extensive epidural pneumorrhachis in the spinal canal from the cervical to sacral vertebrae. The patient was diagnosed with perforation of the rectal anastomosis and retroperitoneal abscess. Antibiotics were administered, and the abscess cavity was reduced on the follow-up CT. Pneumorrhachis in the spinal canal is often found only in the cervical, thoracic, or lumbar regions and is rarely found in the entire spinal canal. Spinal pneumorrhachis resulting from perforation of the colon or rectum has only been reported in 6 previous cases. To differentiate diseases that cause pneumorrhachis in the spinal canal, retroperitoneal abscess, and emphysema associated with perforation of the colon and rectum should be considered., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Quercitrin is a dietary flavonoid widely found in plants with various physiological activities. However, whether quercitrin alters gut microbiota in vivo is not well understood. The aim of this study was to investigate metabolism of quercitrin in the colon and its regulation on gut microbiota in mice., Results: Herein, 22 flavonoids related to quercitrin metabolism were identified based on ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Gas chromatography and 16S rDNA gene sequencing were used to investigate short-chain fatty acid (SCFA) content and diversity of composition of gut microbiota, respectively. The results showed that quercitrin significantly alters the beta-diversity of the gut microbiota, probiotics such as Akkermansia and Lactococcus were significantly increased, and the production of propanoate, isovalerate and hexanoate of the quercitrin group were enhanced significantly. The Spearman's association analysis provided evidence that Gardnerella and Akkermansia have obvious correlations with most of quercitrin metabolites and SCFAs., Conclusion: Quercitrin and its metabolites in the colon altered the structure of the mice gut microbiota and increased the content of SCFAs. Our experiments provide valuable insights into quercitrin research and application. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: The aim of this study was to investigate the frequency dependence of electroacupuncture (EA) in alleviating chronic visceral pain in patients with irritable bowel syndrome (IBS) and the differences in the gut microbiota and metabolites as potential mechanisms to explain frequency dependence., Methods: A visceral hyperalgesia model was established by colorectal instillation of 2,4,6-trinitrobenzene sulfonic acid in rats, and EA treatment at 2/10 Hz, 2/50 Hz and 2/100 Hz was applied at ST25. Visceral sensation was quantified by the abdominal withdrawal reflex score and the area under the curve of the rectus abdominis electromyogram in response to colorectal distension. Ultrastructural morphological damage of colonic tissue of the rats was examined by transmission electron microscopy. 16S rRNA gene sequencing and 1H-nuclear magnetic resonance spectroscopy were applied to study the differences in the gut microbiota and to perform metabonomic profiling of the colonic tissue., Key Results: EA at ST25 at different frequencies attenuated chronic visceral pain, ultrastructural morphological damage to colonic tissue and disruption of the gut microbiota in IBS rats. The frequency of 2/100 Hz has more regulatory pathways than 2/10 Hz and 2/50 Hz. In addition, IBS rats exhibited colonic metabolic disorders, and pantothenate was significantly upregulated after EA treatment at different frequencies. Very low-density lipoprotein and 2-hydroxybutyrate were significantly increased in the 2/10 Hz group, while low density lipoprotein, very low-density lipoprotein, 2-hydroxybutyrate, methylmalonate and alpha-hydroxyisobutyric acid were significantly increased in the 2/100 Hz group., Conclusions and Inferences: EA at ST25 at different frequencies attenuated chronic visceral pain through different gut microbiota and metabolic pathways., (© 2024 John Wiley & Sons Ltd.)

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix and in mice fed with EAA-rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable antiproliferative properties.

Background/aims: : Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). In this study, we developed a retractable robot-assisted traction device and evaluated its performance in colorectal ESD., Methods: : An experienced endoscopist performed ESD 18 times on an ex vivo porcine colon using the robot and 18 times using the conventional method. The outcome measures were procedure time, dissection speed, procedure-related adverse events, and blind dissection rate., Results: : Thirty-six colonic lesions were resected from ex vivo porcine colon samples. The total procedure time was significantly shorter in robot-assisted ESD (RESD) than in conventional ESD (CESD) (20.1±4.1 minutes vs 34.3±8.3 minutes, p<0.05). The submucosal dissection speed was significantly faster in the RESD group than in the CESD group (36.8±9.2 mm 2 /min vs 18.1±4.7 mm 2 /min, p<0.05). The blind dissection rate was also significantly lower in the RESD group (12.8%±3.4% vs 35.1%±3.9%, p<0.05). In an in vivo porcine feasibility study, the robotic device was attached to a colonoscope and successfully inserted into the proximal colon without damaging the colonic wall, and ESD was successfully performed., Conclusions: : The dissection speed and safety profile improved significantly with the retractable RESD. Thus, our robotic device has the potential to provide simple, effective, and safe multidirectional traction during colonic ESD.

Purpose: This study aimed to investigate the impact of hepatocyte growth factor (HGF) on colonic morphology and gut microbiota in a rat model of short bowel syndrome (SBS)., Methods: SD rats underwent jugular vein catheterization for total parenteral nutrition (TPN) and 90% small bowel resection [TPN + SBS (control group) or TPN + SBS + intravenous HGF (0.3 mg/kg/day, HGF group)]. Rats were harvested on day 7. Colonic morphology, gut microflora, tight junction, and Toll-like receptor-4 (TLR4) were evaluated., Results: No significant differences were observed in the colonic morphological assessment. No significant differences were observed in the expression of tight junction-related genes in the proximal colon. However, the claudin-1 expression tended to increase and the claudin-3 expression tended to decrease in the distal colon of the HGF group. The Verrucomicrobiota in the gut microflora of the colon tended to increase in the HGF group. The abundance of most LPS-producing microbiota was lower in the HGF group than in the control group. The gene expression of TLR4 was significantly downregulated in the distal colon of the HGF group., Conclusion: HGF may enhance the mucus barrier through the tight junctions or gut microbiome in the distal colon., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This case report presents the findings of colon adenocarcinoma in a young adult male who presented with vague abdominal pain as his only complaint, suspicious of appendicitis. The patient underwent abdominal computed tomography (CT) imaging for further evaluation of his abdominal pain. CT findings showed pericecal fat stranding and prominent lymph nodes concerning for acute appendicitis, but the appendix could not be adequately visualized; due to the indeterminate CT findings, general surgery proceeded to perform an exploratory laparotomy on the patient and removed an appendiceal mass-like structure that was revealed to be invasive adenocarcinoma of the colon per pathology. This case report details the radiological and pathological findings of colorectal adenocarcinoma presenting similarly to acute appendicitis and demonstrates that colorectal adenocarcinoma must be considered on the list of differentials in young adults presenting with abdominal pain and unclear CT imaging., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Key Clinical Message: Primary leiomyosarcoma of the colon is a very rare tumor entity. Because of unspecific findings, diagnostic can be challenging. Most cases are diagnosed in advanced stages with poor overall survival. Unclear histological findings of smooth muscle cell tissue in colon biopsies together with a tumor of the colon wall in computed tomography (CT) imaging should lead to the differential diagnosis of primary colonic leiomyosarcoma and further diagnostic procedures., Abstract: Primary colonic leiomyosarcoma is an extremely rare tumor entity arising from smooth muscle cells in the colon wall. Only 0.1% of all colorectal malignancies are leiomyosarcomas. Most patients are diagnosed in advanced disease stages. The overall survival rates are low, and recurrence rates are high. Only few data regarding the outcome in localized early disease stages are available. We report the case of an early-stage primary leiomyosarcoma of the sigmoid colon treated with surgical resection. We present the case of a 53-year-old male patient who underwent a colonoscopy due to intermittent rectal bleeding. Colonoscopy revealed an intraluminal polypoid growing tumor in the sigmoid colon. A biopsy was performed with inconclusive histological results. A CT scan revealed a process in the sigmoid colon with wall thickening; there was no evidence of metastatic lesions. After laparoscopic oncological resection of the sigmoid colon, histological examination surprisingly revealed a localized high-grade leiomyosarcoma. Primary leiomyosarcoma of the colon is a rare tumor entity and diagnostic can be challenging. Only a few patients with colonic leiomyosarcoma diagnosed in localized early disease stages and treated with complete surgical resection have been reported in the literature. These patients seem to have a better prognosis with longer overall survival. Because of unspecific diagnostic findings and the lack of symptoms in early disease stages, interdisciplinary collaborations between gastroenterologists, radiologists, pathologists, and surgeons are crucial for early diagnosis and treatment., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

The integrity of colonic gland cells is a prerequisite for normal colonic function and maintenance. To evaluate the underlying injury mechanisms in colonic gland cells induced by excessive fluoride (F), forty-eight female Kunming mice were randomly allocated into four groups and treated with different concentrations of NaF (0, 25, 50, and 100 mg F - /L) for 70 days. As a result, the integrity of the colonic mucosa and the cell layer was seriously damaged after F treatment, as manifested by atrophy of the colonic glands, colonic cell surface collapse, breakage of microvilli, and mitochondrial vacuolization. Alcian blue and periodic acid Schiff staining revealed that F decreased the number of goblet cells and glycoprotein secretion. Furthermore, F increased the protein expression of TLR4, NF-κB, and ERK1/2 and decreased IL-6, interfered with NF-κB signaling, following induced colonic gland cells inflammation. The accumulation of F inhibited proliferation via the JAK/STAT signaling pathway, as characterized by decreased mRNA and protein expression of JAK, STAT3, STAT5, PCNA, and Ki67 in colon tissue. Additionally, the expression of CDK4 was up-regulated by increased F concentration. In conclusion, excessive F triggered colonic inflammation and inhibited colonic gland cell proliferation via regulation of the NF-κB and JAK/STAT signaling pathways, leading to histopathology and barrier damage in the colon. The results explain the damaging effect of the F-induced inflammatory response on the colon from the perspective of cell proliferation and provide a new idea for explaining the potential mechanism of F-induced intestinal damage., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Liquid biopsy is rapidly becoming an indispensable tool in the oncologist's arsenal; however, this technique remains elusive in a publicly funded healthcare system, and real-world evidence is needed to demonstrate utility and feasibility. Here, we describe the first experience of an in-house point of care liquid biopsy program at a Canadian community hospital. A retrospective review of consecutive cases that underwent plasma-based next-generation sequencing (NGS) was conducted. Liquid biopsy was initiated at the discretion of clinicians. Sequencing followed a point of care workflow using the Genexus™ integrated sequencer and the Oncomine precision assay, performed by histotechnologists. Results were reported by the attending pathologist. Eligible charts were reviewed for outcomes of interest, including the intent of the liquid biopsy, results of the liquid biopsy, and turnaround time from blood draw to results available. A total of 124 cases, with confirmed or suspected cancer, underwent liquid biopsy between January 2021 and November 2023. The median turnaround time for liquid biopsy results was 3 business days (range 1-12 days). The sensitivity of liquid biopsies was 71%, compared to tissue testing in cases with matched tissue results available for comparison. Common mutations included EGFR (29%), in 86 lung cancer patients, and PIK3CA (22%), identified in 13 breast cancer patients. Healthcare providers ordered liquid biopsies to inform diagnostic investigations and treatment decisions, and to determine progression or resistance mechanisms, as these reasons often overlapped. This study demonstrates that rapid in-house liquid biopsy using point of care methodology is feasible. The technique facilitates precision treatment and offers many additional advantages for cancer care.

Bacillus cereus (B. cereus) from cow milk poses a threat to public health, causing food poisoning and gastrointestinal disorders in humans. We identified CwpFM, an enterotoxin from B. cereus, caused oxidative stress and inflammatory responses in mouse colon and colonic epithelial cells. Colon proteomics revealed that CwpFM elevated proteins associated with inflammation and oxidative stress. Notably, CwpFM induced activation of the NLRP3/NF-κB signaling, but suppressed antioxidant NFE2L2/HO-1 expression in the intestine and epithelial cells. Consistently, CwpFM exposure led to cytotoxicity and ROS accumulation in Caco-2 cells in a dose-dependent manner. Further, NAC (ROS inhibitor) treatment abolished NLRP3/NF-κB activation due to CwpFM. Moreover, overexpression of Nfe2l2 or activation of NFE2L2 by NK-252 reduced ROS production and inhibited activation of the NLRP3/NF-κB pathway. Inhibition of NF-κB by ADPC and/or suppression of NLRP3 by MCC950 attenuated CwpFM-induced inflammatory responses in Caco-2 cells. Collectively, CwpFM induced oxidative stress and NLRP3/NF-κB activation by inhibiting the NFE2L2/HO-1 signaling and ROS accumulation, leading to the development of intestinal inflammation. Our data elucidate the role of oxidative stress and innate immunity in CwpFM enterotoxicity and contribute to developing diagnostic and therapeutic products for B. cereus-related food safety issues., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background & Aims: Addition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis., Methods: Mice with constitutive deletion of intestinal epithelial sialylation (IEC Slc35a1 -/- mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC Slc35a1 -/- mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and mutiomics studies., Results: IEC Slc35a1 -/- mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC Slc35a1 -/- mice had spontaneous tumors in the rectum greater than the age of 12 months. TM-IEC Slc35a1 -/- mice were highly susceptible to acute inflammation induced by 1% dextran sulfate sodium versus control animals. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC Slc35a1 -/- mice showed altered microbiota with an increase in Clostridia disporicum, which is associated a global reduction in the abundance of at least 20 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil led to more severe small intestine mucositis in the IEC Slc35a1 -/- mice versus wild-type littermates, which was associated with reduced Lgr5 +  cell representation in small intestinal crypts in IEC Slc35a1 -/-;Lgr5-GFP mice., Conclusions: Loss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Colorectal neoplasms are prevalent in patients with chronic kidney disease (CKD); however, the safety and efficacy of colorectal endoscopic submucosal dissection (ESD) are not well understood. This retrospective analysis included ESD procedures performed in 1266 patients with CKD across five tertiary medical institutions from January 2015 to December 2020. Patients were categorized based on their estimated glomerular filtration rate (eGFR), which ranged from CKD1 to CKD5 (including those on dialysis). We found that en bloc resection rates remained high across all CKD stages, affirming the procedural efficacy of ESD. Notably, the prevalence of cardiovascular comorbidities, such as ischemic heart disease and diabetes mellitus, significantly increased with an advancing CKD stage, with a corresponding increase in the Charlson Comorbidity Index, highlighting the complexity of managing these patients. Despite these challenges, the complete resection rate was lower in the CKD5 group (50%) than in the CKD1 group (83.4%); however, procedural complications, such as perforation and bleeding, did not significantly differ among the groups. The predictive models for complete resection and major complications showed no significant changes with a decreasing eGFR. These findings underscore that ESD is a feasible and safe treatment for colorectal neoplasms in patients with CKD, successfully balancing the inherent procedural risks with clinical benefits.

Tissue regeneration after damage is generally thought to involve the mobilization of adult stem cells that divide and differentiate into progressively specialized progeny. However, recent studies indicate that tissue regeneration can be accompanied by reversion to a fetal-like state. During this process, cells at the injury site reactivate programs that operate during fetal development but are typically absent in adult homeostasis. Here, we summarize our current understanding of the molecular signals and epigenetic mediators that orchestrate "fetal-like reversion" during intestinal regeneration. We also explore evidence for this phenomenon in other organs and species and highlight open questions that merit future examination., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)