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While most microbiome research has focused on bacteria, the gut mycobiome—comprising fungal communities such as Candida , Saccharomyces , and Malassezia —is increasingly recognised as an important contributor to intestinal health and disease. In inflammatory bowel disease (IBD), alterations in fungal composition have been linked to immune activation and mucosal inflammation . Certain fungi can interact with host immune receptors, triggering pro-inflammatory pathways and influencing intestinal barrier integrity . Genetic susceptibility factors in IBD may also alter host responses to fungal antigens. Understanding the mycobiome expands the concept of dysbiosis beyond bacteria and highlights new potential therapeutic targets aimed at modulating fungal–immune interactions in intestinal inflammation .

Shift away from pro-inflammatory T cells: They dampen Th1/Th17-type responses and reduce inflammatory cytokine signalling. Boost regulatory networks: They expand regulatory T cells (Tregs) and increase anti-inflammatory mediators (often including IL-10 and TGF-β–linked pathways). Promote type-2 immunity and repair: Helminths induce Th2-biased responses and stimulate epithelial repair mechanisms (mucus production, goblet cell activity, barrier reinforcement). Reprogram innate immunity: They polarise macrophages toward an M2/regulatory phenotype , temper dendritic cell activation, and can stabilise mast cell/innate signalling. Microbiome and metabolite effects: Helminths can indirectly modify bacterial communities and metabolites, potentially reducing dysbiosis-driven inflammation. Evidence and clinical potential (where we stand) Human trials of live helminths (notably Trichuris suis ova and Necator americanus ) have shown mixed and often disappointing efficacy , with variable colonization, dosing challenges, and inconsistent endpoints. Benefit, when seen, appears limited to subsets and is not reliably reproducible. Safety/tolerability: Generally acceptable in controlled studies, but real-world scalability raises concerns: symptom burden, anemia/nutrient effects (species-dependent), immunosuppressed-host risk, and regulatory complexity of administering live organisms. Where the field is heading: The most promising path is moving from “worms” to defined helminth-derived molecules (secreted proteins/EVs) or synthetic analogs that deliver immunoregulatory effects without infection , plus better patient stratification (phenotype, microbiome, immune signatures). Bottom line: Helminths provide a compelling immunology blueprint for IBD immune regulation, but live helminth therapy is unlikely to become mainstream ; helminth-inspired biologics and precision targeting are the more realistic future.

Live bacterial therapeutics (LBTs) represent an emerging “living medicine” strategy for colorectal cancer (CRC), designed for both detection and treatment by exploiting the natural ability of certain bacteria to localize within the gut lumen, mucus layer, and tumor-associated niches. Several therapeutic approaches are under development. Fecal microbiota transplantation (FMT) can broadly modify the gut ecosystem but has limitations due to donor variability and poor reproducibility, making it less suitable for precise CRC detection. Engineered probiotics , based on well-characterized food-grade bacteria, offer improved safety and manufacturing control but may require repeated dosing because of limited long-term colonization. Engineered native bacteria , derived from host-adapted commensals, may achieve better persistence but pose challenges related to personalization and regulatory standardization. Advances in synthetic genetic circuit engineering allow bacteria to sense tumor signals and generate programmed responses, though maintaining genetic stability and safety remains challenging. For detection, engineered bacteria follow a “tumor cue → bacterial sensor → measurable output” model. Tumor-associated signals such as hypoxia, inflammatory metabolites, or altered nutrient environments can trigger bacterial reporters detectable in stool or urine , enabling non-invasive monitoring. Therapeutically, bacteria may deliver immunomodulators, cytotoxic proteins, or prodrug-activating enzymes , with controlled release mechanisms such as quorum-sensing circuits. Robust biocontainment strategies , including kill-switch systems and antibiotic-sensitive strains, are essential for safe clinical translation of these innovative therapies.

Early-life intestinal viral infections may play an important role in shaping long-term gut health. During infancy, the immune system and gut microbiome are still developing, making this a critical window for immune education. Certain viruses can influence how the immune system learns to distinguish between harmful pathogens and beneficial microbes. These early interactions may affect susceptibility to gastrointestinal diseases later in life, including inflammatory bowel disease and other immune-mediated conditions. Maternal antibodies and early immune responses also help guide the development of protective immunity. Understanding these early virus–host interactions may help explain lifelong patterns of gut health and disease risk.

The gut–liver axis plays a central role in the development and progression of metabolic dysfunction–associated steatotic liver disease (MASLD). Increasing evidence suggests that the intestinal microbiome acts as a key regulator of hepatic inflammation, metabolic signaling, and disease severity . Because the liver receives nearly 70% of its blood supply from the portal circulation, it is continuously exposed to microbial metabolites, endotoxins, and immune signals originating from the gut. In MASLD, alterations in gut microbial composition—often referred to as dysbiosis —can promote increased intestinal permeability and enhanced translocation of bacterial products such as lipopolysaccharides and microbial metabolites . These molecules activate hepatic immune pathways, contributing to inflammation, steatohepatitis, and fibrosis progression . Recent research has focused on developing diagnostic tools that incorporate microbiome-derived biomarkers to better predict disease severity. Metagenomic sequencing, microbial metabolite profiling, and microbiome-based predictive models are being explored as potential non-invasive approaches to distinguish simple steatosis from steatohepatitis and advanced fibrosis . In addition, specific microbial metabolic pathways—such as those involved in short-chain fatty acid production, bile acid metabolism, and ethanol generation by gut bacteria —have been linked to MASLD progression. Understanding the microbiome’s influence at the gut–liver interface may ultimately allow clinicians to develop novel diagnostic strategies and targeted therapies , including microbiome modulation through diet, probiotics, or microbiota-directed treatments.

The gut microbiome–host–nutrition axis represents a dynamic system in which diet directly influences microbial composition, metabolic activity, and ultimately gastrointestinal health. This relationship is particularly critical in early life , when the microbiome is still developing and can have long-lasting effects on immune maturation, metabolism, and disease susceptibility. Dietary components such as fiber, complex carbohydrates, fermented foods, and prebiotic substrates provide nutrients that shape microbial diversity and function. In contrast, highly processed diets and excessive simple sugars can promote dysbiosis , which has been associated with conditions such as inflammatory bowel disease, functional gastrointestinal disorders, obesity, and metabolic liver disease . Early-life exposures—including breastfeeding, complementary feeding practices, and antibiotic exposure—also play a key role in determining long-term microbiome patterns. Recent research has begun to integrate microbiome sequencing with predictive nutritional models , enabling researchers to better understand how specific foods influence microbial metabolic outputs and host responses. These insights are paving the way for microbiome-informed dietary strategies , where nutrition interventions are designed to selectively promote beneficial microbial pathways. In clinical practice, practical approaches include increasing dietary fiber, encouraging diverse plant-based foods, promoting fermented foods when appropriate, and limiting ultra-processed foods . Particularly in pediatric populations, these strategies may help guide microbiome development and support long-term gastrointestinal and metabolic health .

The concept of “food as medicine” is gaining increasing recognition as a practical strategy for preventing and managing chronic diseases, particularly those affecting the gastrointestinal system. Dietary patterns play a central role in the development and progression of conditions such as obesity, metabolic dysfunction–associated steatotic liver disease (MASLD), inflammatory bowel disease, and functional gastrointestinal disorders . As a result, modern healthcare is increasingly emphasizing the integration of nutrition directly into clinical care. Culinary medicine is an emerging interdisciplinary field that combines nutrition science, clinical medicine, and culinary skills to help patients translate dietary recommendations into practical, sustainable eating habits. The field originated from programs developed in academic medical centers, where physicians, dietitians, and chefs collaborate to teach patients and healthcare professionals how to prepare healthy, disease-specific meals. In pediatric gastroenterology, culinary medicine offers unique opportunities. Early dietary interventions can influence lifelong metabolic health, gut microbiome development, and gastrointestinal function . Practical applications include structured programs for children with obesity, fatty liver disease, celiac disease, and functional GI disorders , where hands-on cooking education can improve adherence to therapeutic diets. Importantly, culinary medicine shifts the focus from restrictive dieting toward empowering families with practical food skills and culturally appropriate dietary choices . By bringing healthcare into the kitchen, clinicians can bridge the gap between medical advice and everyday eating behaviors, making nutrition a more effective therapeutic tool.

The widespread use of GLP-1–based therapies (e.g., semaglutide, tirzepatide) has transformed obesity management by directly targeting central appetite regulation, satiety pathways, and gastric emptying . These agents significantly reduce energy intake and promote weight loss, but they also challenge traditional nutrition paradigms that focused primarily on calorie restriction and behavioral dietary control . With GLP-1 therapy, weight loss is driven largely by pharmacologically mediated appetite suppression , meaning patients often experience reduced hunger, early satiety, and lower overall food intake. While this improves weight outcomes, it also raises new nutritional concerns. Reduced caloric intake can lead to loss of lean body mass, inadequate protein intake, and micronutrient deficiencies , particularly if nutritional counseling is not integrated into treatment. Therefore, modern obesity care in the GLP-1 era must shift from simply “eating less” to strategic nutrition planning that preserves metabolic health and body composition . Key strategies include prioritizing protein intake, maintaining adequate micronutrient consumption, ensuring hydration, and incorporating resistance exercise to preserve muscle mass during weight loss. Clinicians should also recognize that GLP-1 therapies may alter meal patterns and dietary tolerance , with smaller, more frequent meals often better tolerated than large portions. Overall, the emerging paradigm emphasizes combining pharmacotherapy with targeted nutritional support . Rather than replacing lifestyle interventions, GLP-1 therapies require more precise nutrition guidance to optimize weight loss, preserve lean mass, and sustain long-term metabolic health.

The gastrointestinal tract is protected by multiple layers of defense. After the epithelial and vascular barriers , the mucosal immune system acts as the second major line of defense , maintaining a delicate balance between tolerance to beneficial microbiota and protection against pathogens. Unlike systemic immunity, the adaptive mucosal immune system is uniquely tuned to the intestinal environment , where trillions of commensal microbes coexist with the host. Immune responses are therefore triggered only when microbial antigen exposure crosses a high threshold , preventing unnecessary inflammation against harmless microbiota. A central component of mucosal immunity is the production of secretory IgA antibodies by B cells. These antibodies coat intestinal microbes and limit their interaction with the mucosal surface without causing tissue-damaging inflammation. Interestingly, IgA responses are highly durable and dynamic —rather than fading over time, IgA-producing cells are continually replaced to maintain long-term microbial control. T cells also play a crucial regulatory role. Memory T cells in the intestinal mucosa can persist and cycle even in the absence of ongoing antigen exposure , ensuring rapid responses if microbial balance is disturbed. Importantly, mucosal immune responses show features of “semi-innate” behavior . B cells often use conserved VDJ gene sequences with a limited repertoire, while T cells converge on shared effector pathways that allow rapid responses. Together, this specialized immune system allows the gut to maintain tolerance to beneficial microbes while remaining prepared to defend against potential threats.

The gastrointestinal tract maintains health through two closely linked protective systems: the epithelial barrier and the vascular barrier . While the epithelial barrier—formed by tight junctions between intestinal epithelial cells—prevents luminal microbes and toxins from entering the tissue, the gut vascular barrier (GVB) represents a second critical checkpoint that regulates what passes from the intestinal mucosa into the systemic circulation. The vascular barrier consists of intestinal endothelial cells, pericytes, basement membrane components, and immune signaling pathways that tightly control vascular permeability. Under normal conditions, this barrier prevents bacteria, endotoxins, and inflammatory molecules from entering the bloodstream while allowing selective transport of nutrients and immune mediators. Disruption of the gut vascular barrier has been increasingly recognized in several gastrointestinal disorders. In conditions such as inflammatory bowel disease, liver cirrhosis, and metabolic diseases , increased vascular permeability may allow bacterial products and inflammatory mediators to translocate into the portal circulation. This process can contribute to systemic inflammation, liver injury, and disease progression . Recent research highlights that the epithelial and vascular barriers function as a coordinated defense system . When epithelial integrity is compromised, the vascular barrier acts as a secondary protective filter. However, when both barriers fail, microbial translocation and immune activation can occur. Understanding the biology of the gut vascular barrier is opening new avenues for therapeutic strategies aimed at restoring intestinal barrier integrity and preventing systemic inflammation in gastrointestinal diseases .

Gastrointestinal (GI) care plays a critical role in the long-term management of patients after liver transplantation. Successful outcomes depend on maintaining adequate immunosuppression to prevent graft rejection while minimizing complications related to immunosuppressive medications and the altered immune state. The most commonly used immunosuppressive agents include calcineurin inhibitors (tacrolimus or cyclosporine), corticosteroids, and antimetabolites such as mycophenolate mofetil . While these drugs are essential for graft survival, they frequently have gastrointestinal side effects , including nausea, diarrhea, mucosal injury, and an increased risk of infections. In addition, prolonged immunosuppression predisposes patients to opportunistic infections such as cytomegalovirus, Clostridioides difficile, and other enteric pathogens. Liver transplant recipients may also develop inflammatory and structural GI disorders , including peptic ulcer disease, biliary complications, post-transplant lymphoproliferative disorders, and malignancies of the gastrointestinal tract. Medication-related diarrhea and malabsorption can further complicate nutritional status and drug absorption. Importantly, gastrointestinal diseases can directly influence graft function and immunosuppressive drug levels . Conditions such as severe diarrhea or intestinal inflammation may alter drug absorption, potentially leading to under-immunosuppression and risk of rejection or, conversely, drug toxicity. Optimal care therefore requires close collaboration between hepatologists, gastroenterologists, transplant surgeons, and infectious disease specialists to recognize complications early, adjust immunosuppressive therapy appropriately, and maintain both graft health and overall gastrointestinal function.

Modern cirrhosis care is increasingly proactive: identify clinically significant portal hypertension (CSPH) non-invasively , start disease-modifying therapies early , and prevent first or recurrent decompensation (ascites, variceal bleeding, encephalopathy). 1) Risk stratification using non-invasive portal hypertension assessment Guideline frameworks (Baveno VII) emphasize transient elastography plus platelets to classify risk without HVPG in many patients: LSM ≥25 kPa “rules in” CSPH , while LSM ≤15 kPa with platelets ≥150×10⁹/L “rules out” CSPH in appropriate settings, helping decide who needs NSBBs and who can avoid unnecessary interventions. Refinements and sequential algorithms (e.g., combining Baveno criteria with other scores) aim to improve accuracy, especially for “grey-zone” patients. 2) Disease-modifying therapies to prevent first and recurrent decompensation The major paradigm shift: non-selective beta-blockers (NSBBs), particularly carvedilol in appropriate patients, are not just ‘anti-bleed’ drugs—they can reduce decompensation risk in compensated cirrhosis with CSPH. Alongside NSBBs, “disease modification” also means aggressively treating the driver (HBV/HCV cure, alcohol cessation, MASLD risk reduction) and systematically preventing triggers (infection, AKI, varices) using guideline-concordant pathways. 3) Translating evidence into real-world strategy A practical approach is: (i) confirm/estimate CSPH using TE+platelets, (ii) start NSBBs when CSPH is present and there are no contraindications, (iii) pair with etiology treatment and complication-prevention bundles , and (iv) reassess risk over time as liver stiffness and platelets change.

Recent advances in focal liver lesion (FLL) care are less about “new gadgets” and more about doing the right test for the right patient , earlier—while linking imaging to risk factors, surveillance, and treatment pathways. 1) Risk-factor modification now sits upfront. In practice, the highest-yield “FLL intervention” is often reducing background liver risk—addressing MASLD/obesity, diabetes, alcohol, and viral hepatitis —because these drive progression to cirrhosis and HCC, which changes how every lesion is interpreted and managed. 2) Surveillance is becoming more tailored. Major guidance emphasizes risk-based surveillance (not population-wide), and increased use of standardized imaging systems to reduce ambiguity, especially in at-risk livers. 3) Imaging progress: standardization + higher confidence characterization. LI-RADS continues to anchor communication and decision-making for lesions in patients at risk for HCC, improving consistency across centers. Contrast-enhanced ultrasound (CEUS) and hepatobiliary contrast MRI are increasingly used to “rescue” indeterminate lesions and reduce unnecessary biopsies—while recognizing atypical patterns and pitfalls. 4) Therapy is more stage- and context-specific. For malignant lesions, management is increasingly framed around multidisciplinary pathways and appropriate selection among ablation, resection, and transarterial/systemic options , rather than one default approach.

GLP-1 receptor agonists (GLP-1 RAs), widely used for type 2 diabetes and obesity , are increasingly being studied in patients with inflammatory bowel disease (IBD). Real-world evidence suggests that these agents are generally safe in IBD , with no consistent signal of increased disease flares. In patients with metabolic comorbidities, GLP-1 RAs improve weight, glycemic control, and cardiometabolic risk factors , which are increasingly relevant in modern IBD populations. Beyond metabolic benefits, emerging experimental and translational data suggest that GLP-1 signaling may exert anti-inflammatory effects within the gut. Potential mechanisms include improved intestinal barrier integrity, modulation of immune responses, and effects on the gut microbiome . These observations have generated interest in whether GLP-1 RAs could have disease-modifying effects in IBD, particularly when combined with biologic therapies. However, robust prospective clinical trials in IBD populations are still limited. Endoscopically, clinicians should be aware that GLP-1 RAs delay gastric emptying , which may influence pre-procedure fasting and sedation planning for upper GI endoscopy. Nutritional considerations are particularly important. While weight loss may benefit obese patients, GLP-1 therapy can also reduce appetite and caloric intake, potentially worsening protein-energy malnutrition or sarcopenia , which already affect many IBD patients. Overall, GLP-1 RAs appear clinically safe and metabolically beneficial , but their potential anti-inflammatory and disease-modifying roles in IBD remain an active area of research .

1) Clinical safety in IBD: what we can say today Across recent observational cohorts and systematic reviews, GLP-1 receptor agonists (GLP-1 RAs) have generally not been associated with higher rates of IBD exacerbation , and several datasets even link GLP-1 RA exposure to lower steroid use, fewer hospitalizations, and fewer surgeries in IBD patients with metabolic comorbidity. Practical cautions remain: GI adverse effects (nausea, early satiety, constipation/diarrhea), dehydration risk during flares, and rare pancreatitis signals highlighted by regulators and post-marketing surveillance. 2) Metabolic effects and the “IBD activity” question For IBD patients with obesity/diabetes, GLP-1 RAs reliably improve weight and metabolic markers (HbA1c, lipids) in available real-world data. The key clinical message: weight benefit is consistent; disease-modifying benefit is plausible but not yet proven in prospective IBD-specific trials . 3) Endoscopic considerations GLP-1 RAs delay gastric emptying , which can influence fasting, bowel prep tolerance, and procedural planning (especially sedation/aspiration risk discussions in upper endoscopy). Programs are increasingly building standardized peri-procedure instructions into endoscopy pathways. 4) Emerging anti-inflammatory and barrier effects: why the hype exists Preclinical and translational literature suggests GLP-1 signaling may reduce intestinal inflammation, support epithelial barrier integrity, and modulate immune-metabolic pathways and the microbiome —biologically aligning with IBD pathophysiology. 5) Combination therapy with biologics: where this could go The “next step” is prospective trials testing GLP-1–based therapy as an adjunct to biologics/small molecules , aiming for dual targets: metabolic risk + intestinal inflammation. At present, this remains an active research direction rather than standard care . 6) Nutritional and body-composition considerations: the underappreciated part IBD patients can be “overweight but under-nourished.” GLP-1–driven appetite suppression can unintentionally worsen: protein–energy intake , sarcopenia/low lean mass , micronutrient deficits (iron, B12, vitamin D), especially during active disease. Current studies often report weight but lack granular nutrition and body-composition outcomes , so clinicians should proactively monitor dietary protein, hydration, electrolytes, and muscle mass/function , not just the scale.

Precision medicine aims to move inflammatory bowel disease (IBD) management from a “one-size-fits-all” approach to individualized care based on genetics, microbiome profiles, immune signatures, and environmental exposures. Emerging research from pre-clinical and longitudinal cohorts suggests that genetic susceptibility markers, microbiome alterations, and immune pathway signatures may help identify individuals at increased risk of developing IBD before clinical disease becomes apparent. However, translating these findings into reliable predictive tools for routine practice remains challenging. In established IBD, precision medicine holds promise for guiding treatment selection and sequencing of biologic or small-molecule therapies . Biomarkers such as C-reactive protein, fecal calprotectin, pharmacokinetic drug monitoring, and emerging molecular signatures may help predict therapeutic response or loss of response. Early work in transcriptomics and microbiome profiling also suggests the potential to identify patients who may respond better to anti-TNF, anti-integrin, or IL-23–targeted therapies . Precision approaches may eventually help determine when therapy can be safely de-escalated in patients achieving deep remission. Despite these advances, several barriers remain. Current biomarkers lack sufficient accuracy, accessibility, and cost-effectiveness for routine individualized decision-making. In addition, most clinical trials still rely on population-based treatment algorithms rather than stratified patient groups. Future progress will depend on integrating multi-omics data, real-world registries, and AI-driven analytics to create clinically usable predictive models. While precision medicine in IBD is advancing rapidly, true individualized therapy remains an evolving goal rather than a current reality.

Perianal fistulas are a common and challenging complication of Crohn’s disease (CD), often requiring a coordinated medical and surgical approach . A key initial step is differentiating Crohn’s-related fistulas from cryptoglandular fistulas . Crohn’s fistulas typically occur in younger patients with known luminal disease and may present as multiple, complex tracts with associated rectal inflammation , whereas cryptoglandular fistulas are usually single, simple tracts arising from infected anal glands without underlying intestinal inflammation. Imaging with pelvic MRI or endoscopic ultrasound plays a central role in defining fistula anatomy and guiding management. Seton placement remains an important early intervention in Crohn’s perianal disease. Setons help maintain drainage, prevent abscess formation, and reduce sepsis while medical therapy is initiated. They are particularly useful in complex fistulas or when active infection is present , but are generally considered a temporary measure rather than definitive therapy . While anti-TNF agents (e.g., infliximab) remain the cornerstone of medical treatment, a significant proportion of patients have persistent or recurrent disease. For refractory cases, emerging options include other biologics such as ustekinumab or vedolizumab , mesenchymal stem cell therapy (e.g., darvadstrocel) , and advanced surgical approaches such as fistula plugs or advancement flaps. Optimal management requires multidisciplinary care , combining accurate imaging, appropriate use of setons, biologic therapy, and newer regenerative treatments to improve healing and reduce recurrence in perianal Crohn’s disease.

Dieulafoy’s lesions and Mallory–Weiss tears are important but often underrecognized causes of acute upper gastrointestinal bleeding. Mallory–Weiss tears occur due to longitudinal mucosal lacerations at the gastroesophageal junction, typically triggered by forceful retching, vomiting, or coughing , leading to a sudden rise in intra-abdominal pressure. In contrast, Dieulafoy’s lesions arise from an abnormally large submucosal artery that erodes through a small mucosal defect, most commonly in the proximal stomach, causing potentially severe bleeding despite minimal mucosal injury. Endoscopy plays a central role in both diagnosis and treatment . For Mallory–Weiss tears, bleeding often stops spontaneously, but persistent bleeding may require endoscopic injection therapy, hemoclips, or thermal coagulation . Dieulafoy’s lesions typically require active endoscopic hemostasis because of the risk of recurrent bleeding. Effective treatment modalities include mechanical therapy (hemoclips or band ligation) and thermal or injection therapies . Current evidence suggests that mechanical methods provide durable hemostasis , particularly for Dieulafoy’s lesions, and are increasingly preferred in modern endoscopic practice.

Gastric antral vascular ectasia (GAVE) remains a common cause of chronic, transfusion-dependent iron deficiency anemia, yet the evidence base for therapy is fragmented and methodologically limited . Much of the published literature consists of small single-center cohorts, heterogeneous case definitions (classic “watermelon” vs diffuse patterns), variable endpoints (hemoglobin rise, transfusion reduction, endoscopic eradication), and short follow-up—making head-to-head comparisons and firm guideline-level conclusions difficult. Recurrence is common across modalities, so long-term outcomes matter as much as immediate hemostasis. Argon plasma coagulation (APC) is widely used because it is accessible, familiar, and relatively inexpensive. Its main limitations are the frequent need for multiple sessions , variable durability, and reduced effectiveness in diffuse or severe disease , with risks that include mucosal injury, ulceration, and (rarely) deeper thermal damage. Radiofrequency ablation (RFA) has gained attention as an alternative that can deliver more uniform superficial ablation over broader areas, potentially improving outcomes in diffuse GAVE or APC-refractory cases. In practice, RFA may offer faster improvement in transfusion requirements for selected patients, but it typically involves higher device cost, specific equipment availability, and operator experience. Adverse events remain uncommon but can include post-procedure pain, superficial ulceration, and bleeding. Decision-making should integrate contextual factors : severity of anemia/transfusion burden, GAVE pattern and extent, comorbidities (cirrhosis/portal HTN, CKD, cardiovascular disease), anticoagulation/antiplatelet needs, anesthesia tolerance, access to repeat procedures, local expertise, and patient preference. A practical approach is to start with APC in typical cases, and escalate to RFA when disease is diffuse, rapidly recurrent, or inadequately controlled despite optimized APC sessions—while planning follow-up around anemia response and recurrence risk.

Malignant upper gastrointestinal (UGI) bleeding is a challenging clinical problem commonly encountered in patients with gastric, esophageal, or duodenal malignancies . Unlike peptic ulcer bleeding, hemorrhage from malignant lesions is often diffuse, friable, and recurrent , making durable hemostasis difficult. Traditional endoscopic approaches—such as injection therapy, thermal cautery, and mechanical clips —have been widely used but often provide only temporary control. Current evidence highlights that endoscopic therapy remains a crucial first-line intervention in the management of malignant UGI bleeding, particularly for achieving rapid hemostasis in acute settings . Successful endoscopic control stabilizes patients, reduces transfusion requirements, and creates an opportunity for subsequent definitive oncologic treatments such as radiotherapy, chemotherapy, or surgery . Recent advances in endoscopic hemostasis have expanded the therapeutic options beyond conventional techniques. Topical hemostatic powders (e.g., mineral or polymer-based sprays) have emerged as effective tools for diffuse tumor bleeding, as they can rapidly cover large bleeding surfaces without the need for precise targeting. Additionally, over-the-scope clips (OTSC) and newer mechanical devices may provide more durable mechanical compression in selected focal bleeding lesions. In clinical practice, the optimal method depends on bleeding characteristics and tumor morphology . Diffuse oozing from friable tumor surfaces may respond best to hemostatic powders , while focal arterial bleeding may still require mechanical clipping or advanced devices. Overall, modern management emphasizes a multimodal strategy , integrating endoscopic therapy with oncologic treatment and supportive care to achieve effective control of malignant UGI bleeding.

Food intolerance is commonly reported by patients with irritable bowel syndrome (IBS), yet the mechanisms underlying these reactions are complex and often differ from classical food allergies. Emerging evidence presented at the meeting highlights the important role of psychological stress in amplifying food-related symptoms in IBS . Stress can influence gastrointestinal function through the brain–gut axis , altering gut motility, intestinal permeability, and immune responses. Under conditions of chronic or acute stress, the intestinal barrier may become more permeable, allowing food antigens to interact with mucosal immune cells . This interaction can trigger a localized immune response involving mast cells, eosinophils, and other inflammatory mediators in the gut mucosa. Activation of these immune pathways can sensitize enteric nerves, leading to visceral hypersensitivity , a hallmark feature of IBS. As a result, normal digestive processes or exposure to certain foods may produce exaggerated pain, bloating, or discomfort. Importantly, this process does not necessarily represent a true IgE-mediated food allergy but rather a stress-modulated immune response to dietary antigens . Clinical observations suggest that stress can therefore lower the threshold for symptom generation after food ingestion , explaining why patients often report fluctuating food intolerances depending on their stress levels. These insights emphasize that IBS management should not focus solely on dietary restriction. A comprehensive approach that includes stress reduction strategies, behavioral therapies, and modulation of gut–brain signaling may be essential to reduce food-related symptoms and improve patient outcomes.

Targeted drug delivery is an important emerging strategy in inflammatory bowel disease (IBD), aimed at improving therapeutic efficacy while minimizing systemic toxicity. One innovative approach discussed at the meeting was “glycocaging,” a strategy in which drugs are chemically “caged” with specific carbohydrate (glyco) moieties that remain inactive until they reach the gastrointestinal tract and are selectively activated by enzymes produced by the gut microbiome. The rationale for glycocaging lies in the unique metabolic capabilities of intestinal microbes. The gut microbiota expresses a diverse array of carbohydrate-active enzymes (CAZymes) capable of degrading complex glycans. By attaching a glycan “cage” to a therapeutic molecule, the drug can remain inactive during systemic circulation and become activated only when microbial enzymes in the colon cleave the glycan , thereby releasing the active drug precisely at the site of inflammation. This approach offers several advantages for IBD therapy. First, it allows site-specific drug activation within the colon , which is particularly relevant for diseases such as ulcerative colitis and colonic Crohn’s disease. Second, it reduces systemic exposure , thereby potentially lowering adverse effects commonly associated with immunosuppressive or anti-inflammatory drugs. Third, glycocaging can improve the pharmacokinetic profile of drugs , protecting them from premature metabolism before reaching the gut. Importantly, advances in metagenomic sequencing now allow researchers to map the enzymatic capabilities of the gut microbiome in detail. By analyzing microbial gene clusters encoding carbohydrate-degrading enzymes, scientists can design glycan cages that are selectively cleaved by specific microbial communities. This enables a microbiome-guided drug design strategy , tailoring drug activation to microbial functions present in the diseased gut. Overall, glycocaging represents a promising intersection of microbiome science, medicinal chemistry, and precision drug delivery , potentially enabling more targeted and safer therapies for patients with IBD.

Live bacterial therapeutics (LBTs) represent a rapidly evolving frontier in colorectal cancer (CRC) research, using engineered or naturally occurring bacteria as diagnostic and therapeutic tools within the gut environment. These “living medicines” exploit the natural ability of bacteria to colonize the gastrointestinal tract and interact with tumor-associated microenvironments. Several major LBT strategies are under investigation. Fecal Microbiota Transplantation (FMT) aims to reshape the gut microbiome and potentially influence CRC risk or treatment response. However, variability in donor microbiota and limited reproducibility make it less suitable as a precise diagnostic or therapeutic platform. Engineered probiotics , typically based on well-characterized strains such as E. coli Nissle or Lactobacillus , offer improved safety and manufacturing control but may show limited long-term colonization in the colon. Engineered native bacteria , derived from host-adapted commensals, may achieve better engraftment and persistence but introduce challenges related to personalization and regulatory standardization. Finally, synthetic genetic circuit engineering enables bacteria to detect tumor-related signals and respond with programmed outputs, though maintaining stability and predictability in vivo remains a key challenge. For CRC detection , engineered bacteria can sense tumor-associated cues—such as inflammatory metabolites, hypoxia, or tumor-specific molecular signals—and convert them into measurable outputs. Clinically feasible outputs include stool-based biomarkers or urinary reporter molecules , enabling non-invasive detection or disease monitoring. In therapeutic applications, bacteria can deliver payloads such as immunomodulatory molecules, cytotoxic proteins, or enzymes that convert inactive prodrugs into active anticancer agents locally within tumors. Controlled release strategies—such as quorum-sensing lysis circuits or inducible promoters —ensure targeted delivery. For clinical translation, safety remains paramount. Key biocontainment strategies include genetic kill switches, antibiotic sensitivity safeguards, auxotrophic strains dependent on specific nutrients, and mechanisms to prevent horizontal gene transfer. Together, these approaches position LBTs as a promising future platform for precision detection and treatment of colorectal cancer .