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

Dogs are increasingly recognized as valuable large animal models for understanding human intestinal diseases, as they naturally develop conditions similar to those in humans, such as Enterohemorrhagic , , inflammatory bowel disease, and ulcerative colitis. Given the similarity in gut flora between dogs and humans, canine intestinal models are ideal for translational research. However, conventional extracellular matrix-embedded organoids present challenges in accessing the lumen, which is critical for gut function.

Importance of rectal over colon status in ulcerative colitis remission: the role of microinflammation and mucosal barrier dysfunction in relapse.

Background: Ulcerative colitis (UC) is a refractory inflammatory disease that affects the rectum and colon, with pivotal involvement of the rectal environment in relapse initiation. This study was conducted in two phases to examine the differences in gene expression between the rectum and colon and to identify relapse factors.

Methods: In ***Study 1, RNA sequencing was performed on biopsies from the colon and rectum of patients with active UC, those with remission UC, and controls.

Advancements in Bovine Organoid Technology Using Small and Large Intestinal Monolayer Interfaces.

Advancing knowledge of gastrointestinal physiology and its diseases critically depends on the development of precise, species-specific in vitro models that faithfully mimic in vivo intestinal tissues. This is particularly vital for investigating host-pathogen interactions in bovines, which are significant reservoirs for pathogens that pose serious public health risks. Traditional 3D organoids offer limited access to the intestinal epithelium's apical surface, a hurdle overcome by the advent of 2D monolayer cultures.

Proinflammatory cytokines suppress stemness-related properties and expression of tight junction in canine intestinal organoids.

Recent advancements in canine intestinal organoid research have paved the way for the development of enhanced in vitro models, crucial for exploring intestinal physiology and diseases. Despite these strides, there is a notable gap in creating specific in vitro models that focus on intestinal inflammation. Our study aims to bridge this gap by investigating the impact of proinflammatory cytokines on canine intestinal epithelial cells (IECs) within the context of organoid models.

Pathogen-epithelium interactions and inflammatory responses in Salmonella Dublin infections using ileal monolayer models derived from adult bovine organoids.

Salmonella enterica serovar Dublin (S. Dublin) is an important enteric pathogen affecting cattle and poses increasing public health risks. Understanding the pathophysiology and host-pathogen interactions of S.

Differential Colonization and Mucus Ultrastructure Visualization in Bovine Ileal and Rectal Organoid-Derived Monolayers Exposed to Enterohemorrhagic .

Enterohemorrhagic (EHEC) is a critical public health concern due to its role in severe gastrointestinal illnesses in humans, including hemorrhagic colitis and the life-threatening hemolytic uremic syndrome. While highly pathogenic to humans, cattle, the main reservoir for EHEC, often remain asymptomatic carriers, complicating efforts to control its spread. Our study introduces a novel method to investigate EHEC using organoid-derived monolayers from adult bovine ileum and rectum.

High-fat diet enhances cell proliferation and compromises intestinal permeability in a translational canine intestinal organoid model.

Background: Emerging evidence underscores the responsiveness of the mammalian intestine to dietary cues, notably through the involvement of LGR5 + intestinal stem cells in orchestrating responses to diet-driven signals. However, the effects of high-fat diet (HFD) on these cellular dynamics and their impact on gut integrity remain insufficiently understood. Our study aims to assess the multifaceted interactions between palmitic acid (PA), cell proliferation, and the intestinal epithelial barrier using a canine colonoid model.

Accessible luminal interface of bovine rectal organoids generated from cryopreserved biopsy tissues.

Developing precise species-specific in vitro models that closely resemble in vivo intestinal tissues is essential for advancing our understanding of gastrointestinal physiology and associated diseases. This is especially crucial in examining host-pathogen interactions, particularly in bovines, a known reservoir for microbes and pathogens posing substantial public health threats. This research investigated the viability of producing bovine rectal organoids from cryopreserved tissues.

Assessment of cytochrome P450 induction in canine intestinal organoid models.

Understanding cytochrome P450 (CYP) enzymes in the canine intestine is vital for predicting drug metabolism and developing safer oral medications. This study evaluates canine colonoids as a model to assess the expression and induction of essential intestinal CYP enzymes.Canine colonoids were cultured in expansion medium (EM) with Wnt-3A and in differentiation medium (DM) without Wnt-3A.

Three-Dimensional Morphogenesis in Canine Gut-on-a-Chip Using Intestinal Organoids Derived from Inflammatory Bowel Disease Patients.

Canine intestines possess similarities in anatomy, microbiology, and physiology to those of humans, and dogs naturally develop spontaneous intestinal disorders similar to humans. Overcoming the inherent limitation of three-dimensional (3D) organoids in accessing the apical surface of the intestinal epithelium has led to the generation of two-dimensional (2D) monolayer cultures, which expose the accessible luminal surface using cells derived from the organoids. The integration of these organoids and organoid-derived monolayer cultures into a microfluidic Gut-on-a-Chip system has further evolved the technology, allowing for the development of more physiologically relevant dynamic in vitro intestinal models.

Case report: Persistent Müllerian duct syndrome and enlarged prostatic utricle in a male dog.

A 1-year-old male intact Miniature Schnauzer mix was presented for chronic intermittent hematuria. Abdominal ultrasonography revealed a large, fluid-filled cystic structure extending cranially and dorsally to the prostate. Computed tomography scan images revealed that the fluid-filled cavity resembled a uterus, with both horns entering the scrotum through the inguinal canal adjacent to the testes.

Ion channel function in translational bovine gallbladder cholangiocyte organoids: establishment and characterization of a novel model system.

The study of biliary physiology and pathophysiology has long been hindered by the lack of models that accurately reflect the complex functions of the biliary system. Recent advancements in 3D organoid technology may offer a promising solution to this issue. Bovine gallbladder models have recently gained attention in the investigation of human diseases due to their remarkable similarities in physiology and pathophysiology with the human gallbladder.

Adult Bovine-Derived Small and Large Intestinal Organoids: Development and Maintenance.

Recent progress in bovine intestinal organoid research has expanded opportunities for creating improved models to study intestinal physiology and pathology. However, the establishment of a culture condition capable of generating organoids from all segments of the cattle intestine has remained elusive. Although previous research has described the development of bovine jejunal, ileal, and colonic organoids, this study marks the first report of successful bovine duodenal and rectal organoid development.

Live probiotic bacteria administered in a pathomimetic Leaky Gut Chip ameliorate impaired epithelial barrier and mucosal inflammation.

Here, we report a pathomimetic Leaky Gut Chip that recapitulates increased epithelial permeability and intestinal inflammation to assess probiotic intervention as live biotherapeutics. We leveraged a mechanodynamic human gut-on-a-chip (Gut Chip) that recreates three-dimensional epithelial layers in a controlled oxygen gradient and biomechanical cues, where the addition of a cocktail of pro-inflammatory cytokines, TNF-α and IL-1β, reproducibly induced impaired epithelial barrier followed by intestinal inflammation. This inflamed leaky epithelium was not recovered for up to 3 days, although the cytokine treatment ceased.

Farm and Companion Animal Organoid Models in Translational Research: A Powerful Tool to Bridge the Gap Between Mice and Humans.

Animal organoid models derived from farm and companion animals have great potential to contribute to human health as a One Health initiative, which recognize a close inter-relationship among humans, animals and their shared environment and adopt multi-and trans-disciplinary approaches to optimize health outcomes. With recent advances in organoid technology, studies on farm and companion animal organoids have gained more attention in various fields including veterinary medicine, translational medicine and biomedical research. Not only is this because three-dimensional organoids possess unique characteristics from traditional two-dimensional cell cultures including their self-organizing and self-renewing properties and high structural and functional similarities to the originating tissue, but also because relative to conventional genetically modified or artificially induced murine models, companion animal organoids can provide an excellent model for spontaneously occurring diseases which resemble human diseases.

Serum 25-hydroxyvitamin D and C-reactive protein and plasma von Willebrand concentrations in 23 dogs with chronic hepatopathies.

Background: Serum concentrations of 25-hydroxyvitamin D (25(OH)VD) and C-reactive protein (CRP) and von Willebrand's factor (vWF) concentration correlate with histopathologic disease grade and stage in chronic inflammatory and fibrotic hepatopathies (CH) in humans.

Objectives: To evaluate serum 25(OH)VD and serum CRP concentrations and plasma vWF concentration and determine if they correlate with histopathologic and biochemical variables in dog with CH.

Animals: Twenty-three client-owned dogs with a histopathologic diagnosis of CH were prospectively enrolled.

Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.

Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines.

Treatment With Hydrolyzed Diet Supplemented With Prebiotics and Glycosaminoglycans Alters Lipid Metabolism in Canine Inflammatory Bowel Disease.

Canine inflammatory bowel disease (IBD) is a chronic, immunologically mediated intestinal disorder, resulting from the complex interaction of genetic, environmental and immune factors. Hydrolyzed diets are used in dogs with food-responsive diarrhea (FRD) to reduce adverse responses to immunostimulatory proteins. Prebiotics (PRBs) and glycosaminoglycans (GAGs) have previously been demonstrated to show anti-inflammatory activity in the intestinal mucosa.

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.

The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling.

Microphysiological Engineering of Immune Responses in Intestinal Inflammation.

The epithelial barrier in the gastrointestinal (GI) tract is a protective interface that endures constant exposure to the external environment while maintaining its close contact with the local immune system. Growing evidence has suggested that the intercellular crosstalk in the GI tract contributes to maintaining the homeostasis in coordination with the intestinal microbiome as well as the tissue-specific local immune elements. Thus, it is critical to map the complex crosstalks in the intestinal epithelial-microbiome-immune (EMI) axis to identify a pathological trigger in the development of intestinal inflammation, including inflammatory bowel disease.

Recapitulation of the accessible interface of biopsy-derived canine intestinal organoids to study epithelial-luminal interactions.

Recent advances in canine intestinal organoids have expanded the option for building a better in vitro model to investigate translational science of intestinal physiology and pathology between humans and animals. However, the three-dimensional geometry and the enclosed lumen of canine intestinal organoids considerably hinder the access to the apical side of epithelium for investigating the nutrient and drug absorption, host-microbiome crosstalk, and pharmaceutical toxicity testing. Thus, the creation of a polarized epithelial interface accessible from apical or basolateral side is critical.

Retrospective evaluation of cyclosporine in the treatment of presumed idiopathic chronic hepatitis in dogs.

Background: The etiology of idiopathic chronic hepatitis (ICH) in dogs is poorly understood, but evidence supports an immune-mediated pathogenesis in some dogs.

Objectives: To describe a case series of dogs with presumed ICH treated with cyclosporine (CsA) with or without concurrent medications and to document the incidence of biochemical remission and factors associated with failure to attain remission.

Animals: Forty-eight client-owned dogs diagnosed with presumed ICH, treatment of which included CsA.

The Gut-Brain Axis in Neurodegenerative Diseases and Relevance of the Canine Model: A Review.

Identifying appropriate animal models is critical in developing translatable and systems for therapeutic drug development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs not only naturally develop a cognitive decline in many aspects including learning and memory deficits, but they also exhibit human-like individual variability in the aging process.

Derivation of adult canine intestinal organoids for translational research in gastroenterology.

Background: Large animal models, such as the dog, are increasingly being used for studying diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between commonly used animal models, such as rodents, and humans, and expand the translational potential of the dog model, we developed a three-dimensional (3D) canine GI organoid (enteroid and colonoid) system.