Immune-mediated inflammatory diseases are undergoing a paradigm shift from treatment of established pathology toward prevention in at-risk individuals. Celiac disease (CeD), driven by an aberrant immune response to dietary gluten in genetically predisposed subjects, represents an ideal model to investigate the transition from tolerance to autoimmunity. Within this framework, potential celiac disease (PCD)-defined by CeD-specific autoantibodies in the absence of villous atrophy-has emerged as a clinically relevant condition whose natural history, heterogeneity, and predictors of progression are increasingly understood. Immunological studies reveal that PCD is characterized by a blunted Th1 response, preserved regulatory pathways, reduced epithelial stress signalling, and incomplete licensing of cytotoxic IELs, preventing tissue destruction. This distinct immunological landscape makes PCD a unique window to dissect mechanisms underlying loss of tolerance and to explore preventive strategies. Only a subset of PCD individuals progress to active CeD, with the highest risk concentrated in the first years following seroconversion, while other even stop producing autoantibodies despite consuming gluten. Clinical management remains controversial, but current guidelines discourage routine gluten-free diet (GFD) in asymptomatic PCD both in children and in adults. In conclusion, PCD represents a heterogeneous but highly informative condition positioned at the crossroads between genetic susceptibility and mucosal damage. The identification of reliable progression markers and the development of targeted preventive interventions could transform CeD management and contribute broadly to the understanding and prevention of organ-specific autoimmunity.

Fecal microbiota transplantation (FMT) has become a powerful experimental tool for dissecting microbiota-driven mechanisms in murine models of gastrointestinal and systemic disease. This review provides a comprehensive methodological and translational overview of FMT in mice, focusing on lessons learned from inflammatory bowel disease (IBD) research and emerging perspectives in short bowel syndrome (SBS). We first outline the fundamental role of the gut microbiota in immune regulation, metabolic homeostasis, and maintenance of epithelial barrier integrity, establishing the rationale for modulating microbial communities through FMT. A detailed methodological analysis follows, highlighting how donor selection, recipient conditioning, sample handling, administration route, and environmental variables critically influence microbial engraftment and experimental reproducibility. The review then synthesizes current evidence from key murine IBD models, demonstrating that FMT can restore epithelial integrity, rebalance adaptive immunity, modulate cytokine networks, and enrich beneficial short-chain fatty-acid-producing taxa. Concepts such as functional engraftment, viability of transferred communities, and host-microbe metabolic interactions are discussed as central determinants of FMT efficacy. Finally, we address the emerging but challenging application of FMT in SBS. Profound alterations in intestinal anatomy, transit, oxygen tension, and substrate availability limit the integration of donor microbiota in SBS models, necessitating adapted strategies such as anaerobic handling, pre-conditioned consortia, synbiotics, and optimized delivery systems. Piglet models and computational approaches for donor-recipient matching are highlighted as promising translational tools. Overall, this review underscores the need for methodological standardization and physiologically tailored approaches to advance the reliability, mechanistic insight, and translational potential of FMT in both IBD and SBS.

Inflammatory bowel disease (IBD), comprising Ulcerative Colitis and Crohn's disease, represent a chronic condition of the gastrointestinal tract characterized by an immunological alteration and weakening of mucosal barrier. Mucosal healing and inflammation resolution have emerged as critical therapeutic goals, strongly associated with sustained remission and improved clinical outcomes. Over the years, numerous studies have explored various therapeutic strategies, with increasing focus on biologics and small molecules. One of the emerging immunological targets in IBD is the interleukin 33 (IL-33) / suppression of tumorigenicity 2 (ST2) axis, which exhibits both proinflammatory and anti-inflammatory functions. Evidence from in-vitro and in-vivo studies highlights the involvement of IL-33/ST2 signaling in epithelial regeneration and mucosal healing, but also in pathogenesis of the disease. Several approaches to modulate this axis have been explored, including monoclonal antibodies, receptor antagonists, and small molecules. Concurrently, in-silico molecular design represents a promising strategy for identifying novel therapeutic agents. In particular, numerous computer-aided drug design (CADD) studies have focused on the IL-33/ST2 complex and its role in maintaining intestinal barrier function. This review provides a comprehensive overview of the IL-33/ST2 axis in IBD, on mucosal healing and potential modulation strategies, such as computational approaches.

Liver biochemical and function tests-alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, prothrombin time, and albumin-are used to screen and identify people with acute and chronic liver disease. Elevations in alanine aminotransferase and aspartate aminotransferase reflect hepatocellular injury, with more urgent evaluation required when the international normalized ratio of prothrombin is prolonged and the bilirubin level elevated. An elevation in alkaline phosphatase reflects a cholestatic process and impaired bile flow. Bilirubin may be elevated with either hepatocellular or cholestatic injury. Albumin, prothrombin time, and bilirubin are tests of hepatic function. Evaluation of abnormal liver tests includes history taking with attention to metabolic risk factors, alcohol, medication, and herbal/dietary supplement, followed by an examination, to determine the etiology of liver injury, acuity of illness, and presence of complications. Abdominal imaging provides information regarding liver morphology, steatosis, biliary dilatation, and portal hypertension. Elastography provides information about fibrosis and steatosis. If no explanation for abnormal liver tests can be determined, extrahepatic causes should be investigated. Liver tests used in the estimation of hepatic fibrosis include the fibrosis-4 index and aspartate aminotransferase-to-platelet ratio index. Many proprietary tests of hepatic fibrosis incorporate liver biochemical tests. Liver tests may also be used in the assessment of prognosis, particularly in people with cirrhosis, alcohol-associated liver disease, and metabolic dysfunction-associated steatotic liver disease. Liver test elevations in critically ill patients often reflect severe hepatocellular injury, whereas liver test elevations often indicate hepatotoxicity in people receiving chemotherapy and immune checkpoint inhibitors. With the availability of many approaches to assessing the diagnosis and severity of liver disease, the role of liver biopsy has become more limited.

Cirrhosis is associated with significant risk of comorbidity and early mortality. Low physical function is common in patients with cirrhosis and could predict prognosis. Cardiorespiratory fitness (CRF), determined by maximal exercise with gas exchange measurement, has proven to predict the risk of mortality and disability in other chronic diseases. In patients with cirrhosis, it could help to inform prognostic stratification to improve care and management in clinical practice. This systematic review aims to determine the association between CRF (VO2Peak, percentage of predicted VO2Peak, Anaerobic Threshold (AT)) and mortality prediction, as well as morbidity prediction in cirrhosis.

Despite considerable advancements in recent decades, mortality and complications following liver resection remain high. The volume-outcome relationship has been the subject of extensive research and offers relevant potential for improvement of surgical outcomes. This review aims to examine the impact of hospital and surgeon volume on patient-relevant outcomes in liver resections and synthesize the available evidence.

This meta-analysis evaluates the prognostic significance of the Prognostic Nutritional Index (PNI) in colorectal cancer (CRC) patients, focusing on overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS).

This article defines diagnostic criteria, and reviews clinical evaluation and management of fecal incontinence, anorectal pain, dyssynergic defecation (DD), and rectal hyposensitivity and hypersensitivity. Diagnostic evaluation includes anorectal manometry, balloon expulsion test (BET), anal ultrasound, magnetic resonance imaging, defecography and neurophysiology testing. FI is defined as recurrent uncontrolled passage of fecal material for 3 months. Management includes antidiarrheals, Kegels exercise, biofeedback therapy, dextranomer injection, surgery, sacral nerve stimulation and translumbosacral neuromodulation therapy (TNT). Anorectal pain lasting seconds to minutes is defined as proctalgia fugax whereas pain lasting more than 30 minutes with puborectalis tenderness is defined as levator ani syndrome. Biofeedback and TNT may be useful. DD is defined by both symptoms of difficult defecation and objective evidence of dyssynergia. Biofeedback therapy is efficacious in DD. Rectal sensory disorders are defined by both anorectal symptoms and increased (hyposensitivity) or decreased (hypersensitivity) sensory thresholds during rectal balloon distension, and sensory biofeedback is useful.

This article describes the development of the Rome V adult and pediatric diagnostic questionnaires. Important updates from the Rome IV versions included improved response scaling, new questions to diagnose 3 additional adult DGBI and 14 additional pediatric DGBI (compared to the Rome IV questionnaires), extra questions to clarify the context of DGBI symptoms for research purposes, and the addition of anatomical images to enhance response accuracy. The performance of the Rome V adult questionnaire was tested in Internet surveys in 15 countries, and the pediatric questionnaires in 4 countries. The results indicate that the new questionnaires generally identify DGBI to a similar degree and with the same demographic patterns as the prior Rome IV versions. The Rome V Questionnaire Committee concluded that these new diagnostic questionnaire versions are well suited for epidemiologic and clinical research of DGBI in the Rome V era for both adult and pediatric populations.

Dysfunctional Gallbladder Disorder (DGBD) and Sphincter of Oddi Disorder (SOD) are possible causes of abdominal pain, biliary obstruction, and acute pancreatitis, and are often invoked when a structural etiology is not obvious. Diagnosis was traditionally based on gallbladder scintigraphy and sphincter of Oddi manometry, both of which have fallen out of favor and are no longer part of the Rome diagnostic criteria. For DGBD, the presence of typical biliary pain and persistence of symptoms despite watchful waiting, and for SOD, objective evidence of biliary obstruction and pancreatitis are now central to the diagnosis. With growing recognition that these disorders have traditionally been over-diagnosed and their treatments - which are risky - have been overused, the approach to cholecystectomy and endoscopic retrograde cholangiopancreatography has become progressively more restrictive. This trend continues in Rome V, although predictors of response to therapy, especially for biliary and pancreatic SOD, are desperately needed.

Rome V provides updated criteria for pediatric disorders of gut-brain interaction (DGBI), replacing age-based subdivisions with a classification based on regions and symptom patterns: abdominal pain disorders, defecation and anorectal disorders, and discomfort disorders. New entities were introduced including biliary pain syndrome, centrally mediated abdominal pain syndrome, functional abdominal bloating, and proctalgia fugax. The term "infantile colic" has been replaced with "infant distress syndrome." Existing criteria for irritable bowel syndrome, functional constipation, and nonretentive fecal incontinence were revised to improve diagnostic clarity and reflect current clinical understanding. Rome V also acknowledges that DGBIs may coexist with other conditions producing gastrointestinal symptoms. These updates are intended to support a more consistent diagnostic framework and guide appropriate management strategies for children and adolescents.

The digestive tract plays a key role in maintaining homeostasis and the general well-being of the human body via complex physiological functions. These gastrointestinal functions include motility; mixing of ingesta with pancreatic, biliary, and enteric secretions; absorption of digested nutrients; and disposal of undigested residues. Such processes usually occur without conscious perception. However, about 30-40% of the general population complain of digestive symptoms, often triggered by meal intake. Most of these people will be labelled as having a disorder of gut-brain interaction (DGBI). The pathophysiology of DGBI is complex, and not only involves bidirectional dysregulation of gut-brain interaction (via the gut-brain axis) but also microbial dysbiosis within the gut, altered mucosal immune function, increased epithelial barrier permeability, visceral hypersensitivity, and abnormal gastrointestinal motility. In this article, normal physiology and pathophysiology of GI function, and processes underlying symptom generation are reviewed. This article provides a thorough appraisal of symptom profiles, pathogenesis and functional tests of the wide array of DGBI.

Symptoms that can be attributed to the gastroduodenal area are classified into five categories: (1) Functional Dyspepsia, with two subcategories that can overlap: Postprandial Distress Syndrome, with meal-induced symptoms of postprandial fullness or early satiation and Epigastric Pain Syndrome, with epigastric pain or burning that does not occur exclusively postprandially; (2) Nausea and Vomiting Disorders, which include three subcategories: chronic nausea and vomiting syndrome; cyclic vomiting syndrome; and cannabinoid hyperemesis syndrome; (3) Excessive Belching Disorders, defined as audible escapes of air from the esophagus or the stomach and classified into 2 subcategories depending on the origin of the refluxed gas: gastric or supragastric belching; (4) Inability to Belch Syndrome, a new category defined by the self-reported inability to belch; and (5) rumination syndrome, defined by the repetitive, effortless regurgitation of recently ingested food into the mouth followed by the reswallowing or expulsion of the food bolus.

Upper gastrointestinal Disorders of Gut-Brain Interaction (DGBI) present from infancy through adolescence. The Rome V criteria have expanded to include DGBI of the esophagus, disorders of air-transit and feeding disorders as well as rumination syndrome, cyclic vomiting, chronic nausea syndrome and functional dyspepsia. This expansion provides a diagnostic framework for patients presenting with chest and throat pain, feeding difficulties, belching, pain with eating, nausea and vomiting. Given the advances in impedance technology and high-resolution manometry, testing plays a greater role in these diagnostic criteria than they have in past Rome iterations. This harmony between symptoms and testing results in more precision in therapeutic approaches that are critically multidisciplinary. The ability to assign new, positive diagnoses across the upper gastrointestinal tract offers new opportunities for pediatric-focused therapeutic trials.

Bowel Disorders (BDs), previously termed functional bowel disorders, are highly prevalent disorders worldwide. These disorders affect individuals across all demographic and socioeconomic groups and have substantial economic, in addition to a significantly reducing quality of life. Since the Rome IV publication in 2016 research in the basic and clinical sciences has provided new insights in epidemiology, etiology, pathophysiology, diagnosis, and treatment of BDs, creating the need to revise the diagnostic framework of BDs. This article presents the updated Rome V classification of BDs in 6 distinct categories: irritable bowel syndrome, chronic constipation, functional diarrhea, functional abdominal bloating, unclassified BD and opioid-induced constipation. Each disorder is defined, followed by sections on epidemiology, rationale for changes from prior criteria, clinical evaluation, pathophysiology and treatment. It is in hope that the Rome V BD Committee will assist clinicians and researchers in improving diagnosis, patient care and scientific endeavors of these common and burdensome disorders.

The past decade has witnessed a tremendous profusion of data on the luminal contents of the gastrointestinal tract and their interactions with the host, many of which have been implicated in the pathophysiology of Disorders of Gut-Brain Interaction (DGBI). The role of food in DGBI-related symptoms has attracted much attention and while many alterations in gut microbiome composition have been described, the multitude of factors that confound study design and interpretation in DGBI has precluded the discovery of a specific microbial "signature". The complexities of the gut barrier, its immune and enteroendocrine systems, so critical to the transmission of signals from lumen to host, continue to be revealed. Along the way, concepts such as the microbiome-gut-brain axis have emerged to explain symptom generation in DGBI, forming the basis for novel diagnostic approaches and therapeutic interventions. Taken together, recent research findings have renewed interest in luminal and enteric phenomena in DGBI.

We identify three centrally mediated disorders of gastrointestinal pain in the context of epidemiology, pathophysiology, clinical evaluation and treatment, including pharmacotherapy, brain-gut behavioral therapy and neuromodulation, with emphasis on the importance of a physician-patient relationship. Centrally mediated abdominal pain syndrome is characterized by chronic continuous abdominal pain. It has two main categories: Category A, where the pain occurs without association with physiological events, while in Category B, there is a variable association of pain with physiological events. It is thought to be predominantly a result of central sensitization with altered processing of visceral pain by spinal and brain networks rather than heightened peripheral afferent nerve excitability. Abdominal migraine is newly recognized in adults with paroxysmal, stereotypical episodes of intense abdominal pain. Narcotic bowel syndrome/opioid-induced gastrointestinal hyperalgesia is characterized by the paradoxical development of, or increases in, abdominal pain associated with continuous or increasing dosages of opioids.

Gastric bronchogenic cyst constitutes a rare form of ectopic bronchogenic cyst, with an estimated incidence of less than 1 in 68,000 to 1 in 42,000. This study reported a case who was preoperatively misdiagnosed as gastrointestinal stromal tumor and reviewed the literature on gastric bronchogenic cyst to summarize its clinical features, diagnosis, treatment, pathological manifestations, and prognosis.