[Wilkie syndrome as a diagnostic challenge in intestinal obstruction: case report]. / Síndrome de Wilkie como reto diagnóstico en obstrucción intestinal: reporte de caso.

Wilkie syndrome is a rare pathology that generates intestinal obstruction due to a decrease of the aortomesenteric angle compromising the third portion of the duodenum. We describe a case of an 18-year-old female patient, diagnosed with Wilkie syndrome, with clinical symptoms of intestinal obstruction and weight loss. The diagnosis was made with abdominal CT. Wilkie syndrome is a rare pathology, which becomes a diagnostic challenge because it presents a similar picture to other more common pathologies. We recommend that it should be suspected in the presence of duodenal obstruction.

Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS.

BACKGROUNDBroadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODSIn this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg/kg 10E8VLS administered alone, or concurrently with 5 mg/kg VRC07-523LS, via s.c. injection to healthy non-HIV-infected individuals.RESULTSEight participants received either 10E8VLS alone (n = 6) or 10E8VLS and VRC07-523LS in combination (n = 2). Five (n = 5 of 8, 62.5%) participants who received 10E8VLS experienced moderate local reactogenicity, and 1 participant (n = 1/8, 12.5%) experienced severe local reactogenicity. Further trial enrollment was stopped, and no participant received repeat dosing. All local reactogenicity resolved without sequelae. 10E8VLS retained its neutralizing capacity, and no functional anti-drug antibodies were detected; however, a serum t1/2 of 8.1 days was shorter than expected. Therefore, the trial was voluntarily stopped per sponsor decision (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], NIH). Mechanistic studies performed to investigate the underlying reason for the reactogenicity suggest that multiple mechanisms may have contributed, including antibody aggregation and upregulation of local inflammatory markers.CONCLUSION10E8VLS resulted in unexpected reactogenicity and a shorter t1/2 in comparison with previously tested bNAbs. These studies may facilitate identification of nonreactogenic second-generation MPER-targeting bNAbs, which could be an effective strategy for HIV-1 immunoprophylaxis and treatment.TRIAL REGISTRATIONClinicaltrials.gov, accession no. NCT03565315.FUNDINGDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

N-Glycosylation-dependent regulation of immune-specific tetraspanins CD37 and CD53.

Tetraspanin proteins play an important role in many cellular processes as they are key organizers of different receptors on the plasma membrane. Most tetraspanins are highly glycosylated at their large extracellular loop; however, little is known about the function of tetraspanin glycosylation in immune cells. In this study we investigated the effects of glycosylation of CD37 and CD53, two tetraspanins important for cellular and humoral immunity. Broad and cell-specific repertoires of N-glycosylated CD37 and CD53 were observed in human B cells. We generated different glycosylation mutants of CD37 and CD53 and analyzed their localization, nanoscale plasma membrane organization, and partner protein interaction capacity. Abrogation of glycosylation in CD37 revealed the importance of this modification for CD37 surface expression, whereas surface expression of CD53 was unaffected by its glycosylation. Single-molecule dSTORM microscopy revealed that the nanoscale organization of CD53 was not dependent on glycosylation. CD37 interaction with its partner proteins CD53 and CD20 was affected by glycosylation in a localization-dependent way, whereas its interaction with IL-6Rα was independent of glycosylation. Surprisingly, glycosylation was found to inhibit the interaction between CD53 and its partner proteins CD45, CD20, and, to a lesser extent CD37. Together, our data show that glycosylation affects the interaction capacity of immune-specific tetraspanins CD37 and CD53, which adds another layer of regulation to immune membrane organization.

Medical consequences of "contingency accommodation" for people seeking asylum: thematic analysis of a survey from professionals working in contingency accommodation.

BACKGROUND: Concerns about the housing of migrants and asylum seekers have escalated since the COVID-19 pandemic. From the use of quasi-detention facilities and so-called contingency accommodation to outbreaks of diphtheria in processing centres, there is a worrying trend to normalise potentially damaging conditions. The aim of this study was to assess the health risks posed by contingency housing for asylum seekers in the UK. METHODS: In this cross-sectional survey, a 10-point online questionnaire was sent to professional networks working with refugees and asylum seekers within the UK. Responses were collected between March 4, and April 11, 2022, using a mixture of convenience and snowballing sampling approach. The objectives of the survey were (1) to identify and document unmet needs, (2) to offer practical support, and (3) to map out services and organisation. The survey was designed by six medical professionals with experience of working with migrants and validated by three doctors who had experience running out-reach medical clinics for asylum seekers within contingency accommodation. Background details of geographical location and occupation were collected, and a combination of closed and open questions were used to collect information across five domains (medical, legal social, integration, and basic essentials) using a social determinants of health framework. A code book thematic analysis using a deductive/inductive hybrid approach was used to identify health and social needs as well as specific rights being denied. FINDINGS: There were 68 responses from around the UK, of which 30 (44%) were health-care professionals, and 38 (56%) were from the wider voluntary sector. 45 (67%) had visited an accommodation site, and 21 (33%) had worked with those living in contingency accommodation in other respects. Respondents reported observations regarding sites across most parts of the UK. Major themes of access to health-care, access to other services, barriers to access, and safeguarding were identified, with subthemes on access to primary care, maternity, and mental health services (eg, "Vast unmet need in mental health provision, several suicide attempts"); access to basic essential services (eg, "Food was not fit for purpose" "[c]hildren often did not receive breakfast"); education, and legal support; and frequent moving and communication. INTERPRETATION: Through several themes we highlight the substantial impact of structural isolation of asylum seekers through contingency housing, its major effects on wellbeing and the exacerbation of health inequities. We are using these results to work with asylum seekers and local non-governmental organisations to campaign for improved housing conditions. Study limitations include sampling bias, and a lack of voices of those with lived experience. FUNDING: None.

TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration.

BACKGROUND: The reactivation of genetic programs from early development is a common mechanism for injury-induced organ regeneration. T-box 3 (TBX3) is a member of the T-box family of transcription factors previously shown to regulate pluripotency and subsequent lineage commitment in a number of tissues, including limb and lung. TBX3 is also involved in lung and heart organogenesis. Here, we provide a comprehensive and thorough characterization of TBX3 and its role during pancreatic organogenesis and regeneration. RESULTS: We interrogated the level and cell specificity of TBX3 in the developing and adult pancreas at mRNA and protein levels at multiple developmental stages in mouse and human pancreas. We employed conditional mutagenesis to determine its role in murine pancreatic development and in regeneration after the induction of acute pancreatitis. We found that Tbx3 is dynamically expressed in the pancreatic mesenchyme and epithelium. While Tbx3 is expressed in the developing pancreas, its absence is likely compensated by other factors after ablation from either the mesenchymal or epithelial compartments. In an adult model of acute pancreatitis, we found that a lack of Tbx3 resulted in increased proliferation and fibrosis as well as an enhanced inflammatory gene programs, indicating that Tbx3 has a role in tissue homeostasis and regeneration. CONCLUSIONS: TBX3 demonstrates dynamic expression patterns in the pancreas. Although TBX3 is dispensable for proper pancreatic development, its absence leads to altered organ regeneration after induction of acute pancreatitis.

A Systematic Comparative Study on the Diagnostic Value of Transabdominal Ultrasound in Patients with Pancreatic Cystic Lesions.

Pancreatic cystic lesions are a frequent incidental finding in abdominal imaging. Despite its usually benign background, a small fraction exhibiting features suspicious for cancerous development demands continuous follow-up or surgical removal. Current guidelines advocate magnetic resonance imaging and endoscopic ultrasound to evaluate the risk of malignancy, whereas transabdominal ultrasound is perceived as subordinate imaging. The objective of this study was to analyze cyst detection rates of latest-generation ultrasound machines compared to magnetic resonance imaging, computed tomography, and endosonographic ultrasound and to determine inter-rater reliability. The results showed that large cysts facilitate their visualization by transabdominal ultrasound while detection rates are independent of the anatomical part of the pancreas in which they were sited. Changes in the pancreatic duct width, a connection to the pancreatic duct system, and the architectural characteristics of cysts are poorly recognized by transabdominal ultrasound compared to magnetic resonance imaging and endoscopic ultrasound. Computed tomography imaging is preferred over transabdominal ultrasound to detect calcifications and regional lymphadenopathy. Even if conducted by experienced investigators, transabdominal ultrasound examinations fail to agree with magnetic resonance imaging scans regarding cyst detection rates (κ = 0.093).

Chronic Constipation in Adults.

Chronic constipation has significant quality-of-life implications. Modifiable risk factors include insufficient physical activity, depression, decreased caloric intake, and aggravating medication use. Chronic constipation is classified as primary (normal transit, slow transit, defecatory disorders, or a combination) or secondary (due to medications, chronic diseases, or anatomic abnormalities). Evaluation begins with a detailed history, medication reconciliation, and physical examination. Routine use of laboratory studies or imaging, including colonoscopy, is not recommended in the absence of alarm symptoms. Patients with alarm symptoms or who are overdue for colorectal cancer screening should be referred for colonoscopy. First-line treatment for primary constipation includes ensuring adequate fluid intake, dietary fiber supplementation, and osmotic laxatives. Second-line therapy includes a brief trial of stimulant laxatives followed by intestinal secretagogues. If the initial treatment approach is ineffective, patients should be referred to gastroenterology for more specialized testing, such as anorectal manometry and a balloon expulsion test. Patients with refractory constipation may be considered for surgery. Those in whom pelvic floor dysfunction is identified early should be referred for pelvic floor therapy with biofeedback while first-line medications, such as bulk or osmotic laxatives, are initiated.

Microbial Spectra and Clinical Outcomes from Endoscopically Drained Pancreatic Fluid Collections: A Descriptive Cohort Study.

Pancreatic pseudocyst (PC) and walled-off necrosis (WON) are dreaded complications of acute pancreatitis. Standard therapy consists of endoscopic ultrasound-guided transmural placement of stents to expedite resolution through internal drainage of fluids or necrotic material. Either double pigtail plastic stents (DPPS) or lumen-apposing metal stents (LAMS), or a combination of both, are available for this purpose. The objective of this study was to examine the impact of different stent types on infection rates in addition to clinical outcome measures such as periprocedural adverse events. We conducted a retrospective study comprising 77 patients who had undergone endoscopic drainage for PC or WON in a pancreatitis tertiary referral center. Analysis revealed that both bacterial and fungal infections occurred more frequently in patients treated with LAMS with or without DPPS compared to DPPS only. The use of antibiotics and antimycotics followed the same pattern. Furthermore, a prolonged length of hospital stay and a higher likelihood of transfer to an intermediate care unit were observed in patients with LAMS with or without DPPS. These differences were eliminated if only WON patients were analyzed. Our data imply that the clinical course is primarily influenced by the complexity of the pancreatic fluid collection (PFC) itself rather than the stent type. Prospective large-scale cohort studies are mandatory to underpin these findings.

Functional Genomic Screening in Human Pluripotent Stem Cells Reveals New Roadblocks in Early Pancreatic Endoderm Formation.

Human pluripotent stem cells, with their ability to proliferate indefinitely and to differentiate into virtually all cell types of the human body, provide a novel resource to study human development and to implement relevant disease models. Here, we employed a human pancreatic differentiation platform complemented with an shRNA screen in human pluripotent stem cells (PSCs) to identify potential drivers of early endoderm and pancreatic development. Deep sequencing followed by abundancy ranking pinpointed six top hit genes potentially associated with either improved or impaired endodermal differentiation, which were selected for functional validation in CRISPR-Cas9 mediated knockout (KO) lines. Upon endoderm differentiation (DE), particularly the loss of SLC22A1 and DSC2 led to impaired differentiation efficiency into CXCR4/KIT-positive DE cells. qPCR analysis also revealed changes in differentiation markers CXCR4, FOXA2, SOX17, and GATA6. Further differentiation of PSCs to the pancreatic progenitor (PP) stage resulted in a decreased proportion of PDX1/NKX6-1-positive cells in SLC22A1 KO lines, and in DSC2 KO lines when differentiated under specific culture conditions. Taken together, our study reveals novel genes with potential roles in early endodermal development.

Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.

Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains conserved among influenza subtypes. We conducted a first-in-human, randomized, open-label, phase 1 clinical trial ( NCT03186781 ) to evaluate a novel ferritin (H2HA-Ferritin) nanoparticle influenza vaccine platform. The H2 subtype has not circulated in humans since 1968. Adults born after 1968 have been exposed to only the H1 subtype of group 1 influenza viruses, which shares a conserved stem with H2. Including both H2-naive and H2-exposed adults in the trial allowed us to evaluate memory responses against the conserved stem domain in the presence or absence of pre-existing responses against the immunodominant HA head domain. Fifty healthy participants 18-70 years of age received H2HA-Ferritin intramuscularly as a single 20-µg dose (n = 5) or a 60-µg dose either twice in a homologous (n = 25) prime-boost regimen or once in a heterologous (n = 20) prime-boost regimen after a matched H2 DNA vaccine prime. The primary objective of this trial was to evaluate the safety and tolerability of H2HA-Ferritin either alone or in prime-boost regimens. The secondary objective was to evaluate antibody responses after vaccination. Both vaccines were safe and well tolerated, with the most common solicited symptom being mild headache after both H2HA-Ferritin (n = 15, 22%) and H2 DNA (n = 5, 25%). Exploratory analyses identified neutralizing antibody responses elicited by the H2HA-Ferritin vaccine in both H2-naive and H2-exposed populations. Furthermore, broadly neutralizing antibody responses against group 1 influenza viruses, including both seasonal H1 and avian H5 subtypes, were induced in the H2-naive population through targeting the HA stem. This ferritin nanoparticle vaccine technology represents a novel, safe and immunogenic platform with potential application for pandemic preparedness and universal influenza vaccine development.

Organoids at the PUB: The Porcine Urinary Bladder Serves as a Pancreatic Niche for Advanced Cancer Modeling.

Despite intensive research and progress in personalized medicine, pancreatic ductal adenocarcinoma remains one of the deadliest cancer entities. Pancreatic duct-like organoids (PDLOs) derived from human pluripotent stem cells (PSCs) or pancreatic cancer patient-derived organoids (PDOs) provide unique tools to study early and late stage dysplasia and to foster personalized medicine. However, such advanced systems are neither rapidly nor easily accessible and require an in vivo niche to study tumor formation and interaction with the stroma. Here, the establishment of the porcine urinary bladder (PUB) is revealed as an advanced organ culture model for shaping an ex vivo pancreatic niche. This model allows pancreatic progenitor cells to enter the ductal and endocrine lineages, while PDLOs further mature into duct-like tissue. Accordingly, the PUB offers an ex vivo platform for earliest pancreatic dysplasia and cancer if PDLOs feature KRASG12D mutations. Finally, it is demonstrated that PDOs-on-PUB i) resemble primary pancreatic cancer, ii) preserve cancer subtypes, iii) enable the study of niche epithelial crosstalk by spiking in pancreatic stellate and immune cells into the grafts, and finally iv) allow drug testing. In summary, the PUB advances the existing pancreatic cancer models by adding feasibility, complexity, and customization at low cost and high flexibility.

[Model systems in gastroenterological research : From animal models to human organoids to the clinic]. / Modellsysteme in der gastroenterologischen Forschung : Vom Tiermodell über humane Organoide in die Klinik.

Over the last few decades, various models have been established within gastroenterological research that have significantly contributed to a better understanding of the (patho)physiological processes of various gastrointestinal (GI) diseases (inflammation, organ injuries, carcinomas). This review will focus on such models including genetically engineered mouse models (GEMMs), xenografts, and organoid-based culture systems. GEMMs laid the foundation for successful modeling of such diseases. These have the decisive advantage that diseases can be assessed in their physiological environment and thus allow the examination of cell-cell communications of various cell types (epithelium, fibroblast, immune cells). However, the discrepancy between the genetic background of mice and humans reflected a pivotal disadvantage that could at least partially be circumvented by transplanting human cells into immunocompromised host animals. The time-consuming and labor-intensive generation of such xenograft models, however, considerably limits their usefulness for timely preclinical drug screenings. Thus, novel organoid-based human cell culture systems from adult stem cells or pluripotent stem cells are a promising human tool for modeling GI diseases. The first results already show their usefulness in the regulation of adult tissue homeostasis, regeneration, and tumor development. In addition, this system can be easily established in clinical diagnostics and thus enables real-time ex vivo pharmacotyping to develop personalized therapy strategies, particularly for cancer patients.

Structures of HIV-1 Neutralizing Antibody 10E8 Delineate the Mechanistic Basis of Its Multi-Peak Behavior on Size-Exclusion Chromatography.

Antibody 10E8 is capable of effectively neutralizing HIV through its recognition of the membrane-proximal external region (MPER), and a suitably optimized version of 10E8 might have utility in HIV therapy and prophylaxis. However, 10E8 displays a three-peak profile on size-exclusion chromatography (SEC), complicating its manufacture. Here we show cis-trans conformational isomerization of the Tyr-Pro-Pro (YPP) motif in the heavy chain 3rd complementarity-determining region (CDR H3) of antibody 10E8 to be the mechanistic basis of its multipeak behavior. We observed 10E8 to undergo slow conformational isomerization and delineate a mechanistic explanation for effective comodifiers that were able to resolve its SEC heterogeneity and to allow an evaluation of the critical quality attribute of aggregation. We determined crystal structures of single and double alanine mutants of a key di-proline motif and of a light chain variant, revealing alternative conformations of the CDR H3. We also replicated both multi-peak and delayed SEC behavior with MPER-antibodies 4E10 and VRC42, by introducing a Tyr-Pro (YP) motif into their CDR H3s. Our results show how a conformationally dynamic CDR H3 can provide the requisite structural plasticity needed for a highly hydrophobic paratope to recognize its membrane-proximal epitope.

Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells.

To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the "stemness" maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.

Functional Genomic Screening During Somatic Cell Reprogramming Identifies DKK3 as a Roadblock of Organ Regeneration.

Somatic cell reprogramming and tissue repair share relevant factors and molecular programs. Here, Dickkopf-3 (DKK3) is identified as novel factor for organ regeneration using combined transcription-factor-induced reprogramming and RNA-interference techniques. Loss of Dkk3 enhances the generation of induced pluripotent stem cells but does not affect de novo derivation of embryonic stem cells, three-germ-layer differentiation or colony formation capacity of liver and pancreatic organoids. However, DKK3 expression levels in wildtype animals and serum levels in human patients are elevated upon injury. Accordingly, Dkk3-null mice display less liver damage upon acute and chronic failure mediated by increased proliferation in hepatocytes and LGR5+ liver progenitor cell population, respectively. Similarly, recovery from experimental pancreatitis is accelerated. Regeneration onset occurs in the acinar compartment accompanied by virtually abolished canonical-Wnt-signaling in Dkk3-null animals. This results in reduced expression of the Hedgehog repressor Gli3 and increased Hedgehog-signaling activity upon Dkk3 loss. Collectively, these data reveal Dkk3 as a key regulator of organ regeneration via a direct, previously unacknowledged link between DKK3, canonical-Wnt-, and Hedgehog-signaling.

Carcinoide atípico de timo en varón de 39 años: Reporte de caso / Atypical carcinoid of thymus in a 39-year-old-man: A case report

RESUMEN El carcinoide atípico (CA) de timo es la neoplasia más agresiva y rara que surge en el mediastino anterior y que pertenece a los tumores primarios neuroendocrinos de timo. La mayoría de los pacientes son asintomáticos y según la extensión de la enfermedad pueden presentar desde tos, disnea, dolor torácico hasta síndrome de vena cava superior. Esta presentación clínica inespecífica disminuye la probabilidad del diagnóstico temprano que, sumado con el estadio avanzado al debut y la imposibilidad de resección quirúrgica reduce la tasa de supervivencia. El objetivo es dar a conocer la presentación clínica, imagenológica y patológica en un varón de 39 años con CA de timo cuyo diagnóstico definitivo se basó en el estudio histopatológico (morfología carcinoide, mitosis 0-1/2 mm2, necrosis, Ki 67 = 12%) y marcadores inmunofenotípicos del tumor (CD 56 (+), Panqueratina (+), Sinaptofisina (+), TTF -1 (-)).

ABSTRACT The atypical carcinoid (AC) of thymus is the most aggressive and uncommon neoplasm in the anterior mediastinum, that belongs to the neuroendocrine primary tumors of thymus. Most patients are asymptomatic and according to the disease extension they may present with cough, dyspnea, chest pain, and superior cava vein syndrome. This non-specific clinical presentation reduces the likelihood for making an early diagnosis; and this, together with disease stage and lack of surgical resection reduces the survival rate. The aim of this paper is to describe the clinical presentation in a 39-year old male with thymus carcinoid whose diagnosis was based on histopathological studies (carcinoid morphology, 0-1/2 mitoses/mm2), necrosis, Ki67, 12%), and immunophenotypic tumor markers (CD56(+), Pankeratin (+), Synaptophysin (+), and TTF-1 (-)).

RINT1 Regulates SUMOylation and the DNA Damage Response to Preserve Cellular Homeostasis in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) still presents with a dismal prognosis despite intense research. Better understanding of cellular homeostasis could identify druggable targets to improve therapy. Here we propose RAD50-interacting protein 1 (RINT1) as an essential mediator of cellular homeostasis in PDAC. In a cohort of resected PDAC, low RINT1 protein expression correlated significantly with better survival. Accordingly, RINT1 depletion caused severe growth defects in vitro associated with accumulation of DNA double-strand breaks (DSB), G2 cell cycle arrest, disruption of Golgi-endoplasmic reticulum homeostasis, and cell death. Time-resolved transcriptomics corroborated by quantitative proteome and interactome analyses pointed toward defective SUMOylation after RINT1 loss, impairing nucleocytoplasmic transport and DSB response. Subcutaneous xenografts confirmed tumor response by RINT1 depletion, also resulting in a survival benefit when transferred to an orthotopic model. Primary human PDAC organoids licensed RINT1 relevance for cell viability. Taken together, our data indicate that RINT1 loss affects PDAC cell fate by disturbing SUMOylation pathways. Therefore, a RINT1 interference strategy may represent a new putative therapeutic approach. SIGNIFICANCE: These findings provide new insights into the aggressive behavior of PDAC, showing that RINT1 directly correlates with survival in patients with PDAC by disturbing the SUMOylation process, a crucial modification in carcinogenesis.

Enteropathogenic Infections: Organoids Go Bacterial.

Enteric infections represent a major health care challenge which is particularly prevalent in countries with restricted access to clean water and sanitation and lacking personal hygiene precautions, altogether facilitating fecal-oral transmission of a heterogeneous spectrum of enteropathogenic microorganisms. Among these, bacterial species are responsible for a considerable proportion of illnesses, hospitalizations, and fatal cases, all of which have been continuously contributing to ignite researchers' interest in further exploring their individual pathogenicity. Beyond the universally accepted animal models, intestinal organoids are increasingly valued for their ability to mimic key architectural and physiologic features of the native intestinal mucosa. As a consequence, they are regarded as the most versatile and naturalistic in vitro model of the gut, allowing monitoring of adherence, invasion, intracellular trafficking, and propagation as well as repurposing components of the host cell equipment. At the same time, infected intestinal organoids allow close characterization of the host epithelium's immune response to enteropathogens. In this review, (i) we provide a profound update on intestinal organoid-based tissue engineering, (ii) we report the latest pathophysiological findings defining the infected intestinal organoids, and (iii) we discuss the advantages and limitations of this in vitro model.