Trending Topics in Gastroenterology | GastroAGI

Retatrutide in Type 2 Diabetes: Triple Agonist Delivers Powerful HbA1c and Weight Reduction: The Lancet | June 2026

* Retatrutide is a once-weekly injectable triple hormone receptor agonist targeting GIP, GLP-1, and glucagon receptors. * TRANSCEND-T2D-1 evaluated retatrutide as monotherapy in adults with type 2 diabetes inadequately controlled with diet and exercise alone. * The study included 537 patients with early type 2 diabetes, mean HbA1c of 7.9%, mean diabetes duration of 2.5 years, and mean BMI of 35.8 kg/m². * Retatrutide produced significant HbA1c reductions at all tested doses compared with placebo. * Mean HbA1c reduction at 40 weeks was –1.69% with 4 mg, –1.86% with 9 mg, and –1.94% with 12 mg, compared with –0.81% with placebo. * Weight loss was substantial and dose-related, which is especially relevant because weight reduction is often harder to achieve in patients with type 2 diabetes. * Mean bodyweight reduction was –11.5% with 4 mg, –13.9% with 9 mg, and –15.3% with 12 mg, compared with –2.6% with placebo. * The magnitude of weight loss suggests that retatrutide may become important not only for glycaemic control, but also for obesity-driven metabolic disease. * No severe hypoglycaemia was reported, which is reassuring for a therapy used without insulin or sulfonylureas. * The most common adverse events were gastrointestinal, generally mild to moderate, and tended to reduce over time. * Treatment discontinuation due to adverse events was low, occurring in 2%–5% of retatrutide-treated patients. * The study population had relatively early diabetes and was not on background glucose-lowering therapy, so results may not directly apply to patients with long-standing or insulin-treated diabetes. * Long-term cardiovascular, renal, hepatic, and real-world tolerability data will be important before defining its exact place in therapy. * For gastroenterologists, the key relevance is the broader metabolic impact: powerful weight loss may influence future management of MASLD, obesity-related GI disease, and cardiometabolic risk. Bottom line: Retatrutide produced impressive dual benefits in early type 2 diabetes—nearly 2% HbA1c reduction and up to 15% bodyweight loss over 40 weeks—supporting its potential as a major next-generation metabolic therapy.

MLCK1 Targeting Separates ICI Colitis from Antitumor Immunity : Gut | May 2026

Introduction Immune Checkpoint Inhibitors have transformed cancer treatment across multiple malignancies, but immune-related adverse events remain major limitations to durable therapy. Among these toxicities, Immune Checkpoint Inhibitor Colitis is particularly important because it frequently necessitates immunosuppression, treatment interruption or permanent discontinuation of anticancer therapy. Problem Statement Current approaches to immune checkpoint inhibitor colitis broadly suppress immune activity and may compromise antitumor efficacy. Mechanism-specific strategies capable of controlling intestinal toxicity without impairing anticancer immunity remain an unmet clinical need. Summary This mechanistic translational study identifies long myosin light chain kinase 1 (MLCK1) as a central regulator of immune checkpoint inhibitor-induced intestinal barrier dysfunction and demonstrates that targeting this pathway can suppress colitis without reducing antitumor immune activity. Using single-cell RNA sequencing and spatial transcriptomics from human biopsy samples, the investigators demonstrated profound disruption of intestinal tight junction integrity in checkpoint inhibitor colitis. Similar findings were reproduced in murine models designed to closely mimic human immune-mediated colitis. The study showed that immune checkpoint blockade activates an MLCK1-dependent epithelial leak pathway, resulting in impaired intestinal barrier function and enhanced gut permeability. This barrier disruption emerged as a key initiating event driving intestinal inflammation. Mechanistically, tumour necrosis factor released by activated CD4+ and CD8+ T cells was identified as a major upstream trigger of MLCK1 activation. The resulting epithelial tight junction disruption amplified intestinal inflammation and promoted clinically significant colitis. Importantly, genetic deletion of MLCK preserved tight junction architecture and substantially reduced inflammation in murine models, directly confirming MLCK1 as a functional disease driver rather than merely a downstream inflammatory marker. A major translational advance was the identification of Epicatechin as a pharmacologic inhibitor capable of disrupting MLCK1-FKBP8 interaction. This intervention prevented MLCK1 recruitment to the perijunctional actomyosin ring and preserved epithelial barrier integrity. Most importantly, epicatechin-mediated barrier restoration ameliorated checkpoint inhibitor colitis without compromising antitumor efficacy in melanoma and colorectal cancer models. This uncoupling of intestinal toxicity from anticancer immunity represents the study’s most clinically significant finding. The work fundamentally shifts the conceptual framework for immune checkpoint inhibitor colitis. Rather than viewing toxicity solely as uncontrolled systemic immune activation, the study positions epithelial barrier dysfunction as a critical mechanistic amplifier of intestinal inflammation. Clinically, the findings are highly relevant because current management strategies rely predominantly on corticosteroids and systemic immunosuppressants, which may attenuate anticancer immune responses and increase infectious complications. Barrier-directed therapy could therefore represent an entirely new therapeutic paradigm in immune-related adverse event management, focusing on preservation of epithelial integrity rather than broad immune suppression. The study also reinforces the increasingly recognized role of intestinal barrier biology in systemic inflammatory and immune-mediated diseases. Tight junction regulation appears to function as a critical checkpoint controlling mucosal immune amplification during checkpoint inhibitor therapy. Another important implication is the potential role of intestinal permeability biomarkers in predicting or monitoring immune-mediated gastrointestinal toxicity. Early detection of barrier dysfunction could eventually support preemptive intervention strategies. From an oncologic perspective, the ability to maintain effective immunotherapy while minimizing gastrointestinal toxicity could substantially improve treatment durability and patient outcomes across multiple cancer types. Although further clinical validation remains necessary, the findings provide one of the clearest mechanistic demonstrations to date that immune-related toxicity and antitumor efficacy may be biologically separable. Overall, this study identifies MLCK1-mediated epithelial barrier dysfunction as a key driver of immune checkpoint inhibitor colitis and demonstrates that targeted barrier restoration can suppress intestinal inflammation without impairing anticancer immunity, establishing a promising new direction for toxicity-specific immunotherapy management.

Gut Microbiota-Driven NETosis Promotes Endometriosis : Gut | May 2026

Introduction Endometriosis is a chronic inflammatory gynecological disease characterized by ectopic implantation of endometrial tissue and associated with pelvic pain, infertility and impaired quality of life. Although immune dysregulation and gut microbiota alterations have both been implicated in disease pathogenesis, the mechanistic link between intestinal dysbiosis and peritoneal lesion formation has remained poorly understood. Problem Statement The causal mechanisms through which gut microbiota influence peritoneal inflammation and lesion progression in endometriosis remain unclear, particularly regarding microbial translocation, neutrophil activation and the role of Neutrophil Extracellular Traps. Summary This translational study identifies a novel gut–peritoneum axis in endometriosis whereby translocated gut microbiota trigger NETosis and promote lesion development through activation of a distinct proinflammatory neutrophil population. Using single-cell RNA sequencing of peritoneal immune cells, the investigators identified a membrane metalloendopeptidase-positive neutrophil subset enriched in endometriosis and primed for NET formation. These neutrophils released extracellular traps in response to bacterial lipopolysaccharide stimulation, directly enhancing endometrial cell proliferation, migration and lesion establishment. Mechanistically, NETs acted not merely as inflammatory byproducts but as active structural and signaling platforms that facilitated ectopic endometrial implantation and persistence. Importantly, inhibition of NETosis or enzymatic degradation of NETs markedly suppressed endometriosis progression in murine models, highlighting NETosis as a functionally relevant disease driver rather than an epiphenomenon. A major strength of the study was the integration of microbiome source-tracking analyses with functional experimental validation. Faecal microbiota transplantation from patients with endometriosis disrupted intestinal barrier integrity in mice and promoted microbial translocation into the peritoneal cavity. Among translocating organisms, Pseudomonas aeruginosa emerged as a particularly important pathogenic driver. GFP-tagged bacterial experiments demonstrated migration of Pseudomonas into peritoneal lesions, where bacterial lipopolysaccharides triggered NETosis and amplified inflammatory lesion development. These findings significantly expand the emerging concept of microbiota-driven extraintestinal inflammatory disease. Rather than acting indirectly through systemic metabolites alone, gut microorganisms may physically translocate across impaired intestinal barriers into distant compartments, directly driving local immune activation. The work also positions NETosis as a central mechanistic bridge linking microbial dysbiosis, innate immunity and ectopic tissue remodeling in endometriosis. Similar NET-mediated pathways are increasingly recognized across inflammatory, autoimmune and cancer-related conditions, suggesting broader relevance of this inflammatory circuitry. Clinically, the study opens several potentially important therapeutic avenues. Strategies targeting intestinal permeability, selective microbial modulation, Pseudomonas suppression or NETosis inhibition may eventually emerge as novel disease-modifying approaches in endometriosis management. The findings are particularly interesting because they move beyond traditional hormone-centric models of endometriosis pathogenesis. While estrogen signaling remains fundamental, the disease increasingly appears to involve complex immune-microbiome interactions capable of sustaining chronic inflammatory lesion progression. From a translational perspective, the study additionally reinforces the growing importance of cross-disciplinary convergence between gastroenterology, microbiome science, immunology and reproductive medicine. The gut–peritoneum axis described here resembles broader gut-organ inflammatory networks increasingly implicated across systemic diseases. The identification of a disease-associated neutrophil subset also raises the possibility of future biomarker development using immune phenotyping or microbial signatures for disease stratification and therapeutic monitoring. Overall, this study defines a novel gut microbiota–NETosis pathway in endometriosis, demonstrating that translocated gut-derived Pseudomonas activates proinflammatory neutrophils and drives lesion progression through pathogenic NET formation. The findings establish the gut–peritoneum immune axis as a potentially important therapeutic target in endometriosis.

High-Quality Colonoscopic Surveillance Reveals Distinct Neoplasia Patterns in Lynch Syndrome : Gut | May 2026

Introduction Lynch Syndrome remains the most common inherited colorectal cancer predisposition syndrome and is associated with markedly elevated lifetime risk of Colorectal Cancer. High-quality colonoscopic surveillance is central to cancer prevention and early detection in Lynch syndrome, yet much of the historical evidence guiding surveillance intervals and risk stratification derives from cohorts with variable colonoscopy quality standards. Problem Statement Reliable genotype-specific neoplasia detection data from modern high-quality surveillance programs remain limited. Understanding lesion characteristics and risk factors within optimized surveillance settings is essential for refining precision surveillance strategies in Lynch syndrome. Summary This tertiary-center study evaluated nearly 1,000 surveillance colonoscopies performed in patients with Lynch syndrome under exceptionally high-quality colonoscopy standards. The cohort achieved excellent procedural metrics, including very high caecal intubation and bowel preparation adequacy rates, providing a robust framework for accurate neoplasia detection analysis. The study demonstrated a substantial adenoma burden, with adenomas detected in nearly one-third of surveillance procedures. Importantly, most adenomas were located in the proximal colon, reinforcing the well-established right-sided predominance of neoplasia in Lynch syndrome and highlighting the necessity of meticulous proximal colonic examination during surveillance. A notable finding was the predominance of non-advanced and flat adenomas. Flat morphology can make lesions more difficult to detect, emphasizing the importance of optimized withdrawal technique, adequate inspection time and enhanced endoscopic vigilance in hereditary cancer surveillance programs. Despite lower adenoma detection rates in carriers of MLH1 Mutation, this subgroup accounted for half of all colorectal cancers identified. This suggests that carcinogenesis in MLH1-associated Lynch syndrome may proceed more rapidly or through biologically aggressive pathways, potentially narrowing the window for adenoma detection before malignant transformation. Conversely, higher serrated lesion detection rates were observed among MSH6 and PMS2 carriers, suggesting important genotype-specific differences in neoplastic pathways. These findings support the emerging concept that Lynch syndrome is not a single biologic entity but rather a spectrum of molecularly distinct syndromes with differing carcinogenic trajectories. Several clinical factors influenced neoplasia detection. Older age and elevated body mass index were associated with higher adenoma detection rates, while male sex and non-white ethnicity were associated with increased colorectal cancer detection. These observations may help refine individualized surveillance intensity and risk stratification approaches. The study is particularly important because it evaluates surveillance outcomes under modern quality benchmarks. Historically reported interval cancer rates and lesion detection patterns may have been confounded by suboptimal bowel preparation, incomplete examinations or inconsistent withdrawal practices. This work demonstrates that even within high-quality surveillance systems, substantial neoplastic burden persists in Lynch syndrome patients. Clinically, the findings strongly support continued emphasis on colonoscopy quality metrics within hereditary cancer surveillance programs. High-definition imaging, careful proximal inspection and detection of subtle flat lesions remain critical. The data additionally strengthen the rationale for genotype-tailored surveillance protocols rather than uniform surveillance intervals across all mismatch repair gene carriers. The observation that MLH1 carriers developed disproportionate colorectal cancer burden despite lower adenoma detection may eventually justify even more intensive surveillance strategies or adjunctive preventive approaches in selected high-risk genotypes. Overall, this study demonstrates that patients with Lynch syndrome continue to harbor substantial colorectal neoplastic burden despite high-quality surveillance. The findings highlight distinct genotype-specific phenotypes, proximal and flat lesion predominance, and the importance of precision surveillance strategies guided by both colonoscopy quality and underlying mismatch repair genotype biology.

Gut–Testis Axis and Male Reproductive Health : Int J Mol Sci | May 2026

Introduction Emerging evidence suggests that the gut microbiome may play a central regulatory role in male reproductive physiology through a proposed “gut–testis axis.” This concept integrates microbial metabolism, systemic inflammation, endocrine signalling and immune regulation as interconnected determinants of spermatogenesis and sperm quality. With idiopathic infertility accounting for a substantial proportion of male infertility cases, understanding microbiome-mediated reproductive dysfunction has become an important translational research priority. Problem Statement Although associations between diet, metabolic disease and impaired fertility are increasingly recognised, the mechanistic pathways linking gut microbial dysbiosis to testicular dysfunction remain incompletely understood. Existing human studies are largely observational, and causal relationships between microbiome alterations and reproductive impairment require further validation. Summary This comprehensive review synthesises current mechanistic, translational and clinical evidence linking gut microbial dysbiosis to impaired male reproductive health. The authors propose that disruption of intestinal microbial homeostasis contributes to infertility through multiple converging pathways involving endocrine dysfunction, oxidative stress, inflammation, barrier disruption and altered microbial metabolite production. Central to this framework is the concept that beneficial commensal bacteria, particularly short-chain fatty acid (SCFA)-producing taxa such as Bifidobacterium, Lactobacillus and Faecalibacterium, maintain intestinal integrity, regulate immune homeostasis and support metabolic signalling. SCFAs, especially butyrate, appear critical for preserving blood–testis barrier integrity, Sertoli cell maturation and seminiferous tubule development. Germ-free animal models demonstrated impaired gonadotropin production, increased blood–testis barrier permeability and defective spermatogenesis, all of which improved following colonisation with butyrate-producing organisms. The review further highlights amino acid-derived microbial metabolites, particularly L-citrulline, as regulators of testicular homeostasis and nitric oxide signalling. Dysbiosis-associated depletion of L-citrulline impaired Sertoli cell function, promoted oxidative stress and disrupted spermatogenesis in experimental models. Restoration of these pathways through dietary supplementation improved sperm quality and DNA repair responses, supporting a direct microbiota–metabolism–testis connection. Conversely, expansion of proinflammatory pathobionts and endotoxin-producing Gram-negative bacteria was strongly linked to reproductive dysfunction. Lipopolysaccharide-mediated activation of Toll-like receptor pathways in Leydig cells, Sertoli cells and spermatozoa induced inflammatory cytokine production, oxidative stress and apoptosis. These processes impaired testosterone synthesis, disrupted hypothalamic–pituitary–gonadal axis regulation and reduced sperm motility, viability and fertilisation capacity. Several fecal microbiota transplantation studies provided important causal evidence for the gut–testis axis. Transfer of dysbiotic microbiota from high-fat diet, alcohol exposure or metabolic syndrome models into healthy animals reproduced impaired spermatogenesis, reduced sperm motility, mitochondrial dysfunction and inflammatory activation within reproductive tissues. In contrast, microbiota-restorative interventions including high-fibre diets, alginate oligosaccharides, probiotics and microbiota transplantation from healthy donors improved microbial composition, enhanced antioxidant pathways, restored retinoid and bile acid metabolism, and improved sperm quality. Human evidence remains relatively limited but supports similar trends. Western dietary patterns rich in saturated fats, processed foods and refined sugars were consistently associated with poorer semen parameters, while omega-3 fatty acids, fruits and vegetables correlated with improved sperm morphology and motility. Men with metabolic disorders and testosterone deficiency exhibited enrichment of proinflammatory and endotoxin-producing taxa alongside reduced beneficial SCFA-producing organisms. Several microbial taxa, including Prevotella and Ruminiclostridium, demonstrated associations with abnormal sperm parameters and systemic inflammatory profiles. Importantly, the review emphasises major limitations in the field, including heterogeneity in microbiome profiling techniques, lack of longitudinal studies, substantial confounding variables and incomplete mechanistic understanding of how microbial metabolites influence testicular physiology. Despite these limitations, the accumulating evidence strongly supports the gut microbiome as a promising therapeutic target for male infertility and reproductive dysfunction.

Gut Microbiota Diet Index Linked to Lower Mortality and Slower Biological Aging : J Nutr Health Aging | Jun 2026

Introduction The intestinal microbiome has emerged as a major regulator of metabolic health, inflammation and healthy aging. Dietary patterns strongly influence microbial diversity and metabolite production, with fiber-rich and plant-based diets generally promoting beneficial microbial ecosystems. The Dietary Index for Gut Microbiota (DI-GM) was developed to quantify the impact of habitual diet on gut microbial health and has previously been associated with favorable metabolic outcomes in selected disease populations. Problem Statement Although microbiota-supportive dietary patterns may influence longevity, the relationship between DI-GM and premature mortality in the general population has not previously been established. Furthermore, whether biological aging mediates the association between gut microbiota–oriented dietary patterns and survival outcomes remains unclear. Summary This large longitudinal NHANES-based cohort study evaluated more than 15,000 U.S. adults and demonstrated a strong inverse relationship between DI-GM scores and both premature and all-cause mortality. Each one-point increase in DI-GM was associated with approximately 9% lower premature mortality risk and 10% lower overall mortality risk after multivariable adjustment. Individuals with the highest DI-GM scores had substantially lower mortality risk compared with those with the poorest microbiota-associated dietary patterns. Kaplan–Meier analyses and smooth curve modeling further demonstrated a consistent linear relationship between higher DI-GM scores and improved survival outcomes across multiple demographic subgroups. Importantly, the study identified biological aging as a major mediator of this protective association. Measures including PhenoAge acceleration, Klemera–Doubal biological age acceleration and homeostatic dysregulation partially explained the relationship between DI-GM and mortality. Among these, PhenoAge acceleration demonstrated the strongest mediating effect, accounting for more than one-third of the association with premature mortality. Higher DI-GM scores were consistently associated with lower biological age acceleration and reduced physiologic dysregulation. Mechanistically, diets associated with higher DI-GM scores emphasized fiber-rich plant foods, whole grains, legumes, fermented dairy products, tea and coffee while minimizing processed meats, refined grains and high-fat dietary patterns. These dietary profiles likely promote short-chain fatty acid production, improved metabolic homeostasis and reduced chronic inflammation through favorable modulation of gut microbial diversity. Conversely, lower-quality diets may increase production of harmful microbial metabolites such as trimethylamine N-oxide, which has been linked to cardiovascular disease and mortality. Overall, this study strengthens the concept that microbiota-oriented dietary patterns may influence longevity partly through modulation of biological aging processes. The findings support growing interest in gut microbiome–targeted nutritional strategies as scalable public health interventions for promoting healthy aging and reducing premature mortality.

Plant-Based Hospital Menus Maintain Nutritional Adequacy : Frontline Gastroenterol | May 2026

Introduction Healthcare systems are increasingly recognizing the environmental impact of hospital food services, particularly the high carbon footprint associated with meat-heavy diets. At the same time, maintaining adequate nutritional quality for hospitalized patients remains essential, especially in acute care settings where malnutrition and increased metabolic demands are common. Problem Statement Concerns persist that reducing meat-based meals in hospital settings could compromise protein intake and overall nutritional adequacy. Evidence evaluating whether plant-based or meat-free hospital menus can maintain comparable nutritional standards remains limited. Summary This comparative nutrient analysis evaluated whether meat-free and plant-based alternatives could replace traditional meat-based hospital meals without compromising nutritional quality. The original inpatient menu consisted predominantly of meat-containing meals, with a substantial proportion derived from ruminant meats such as beef and lamb, which are associated with high environmental burden. The redesigned menu significantly reduced ruminant meat offerings and incorporated plant-based protein sources including legumes, dairy and eggs. Importantly, the alternative menu maintained comparable caloric, protein and fat content relative to the original menu, demonstrating that nutritionally balanced hospital meals can be achieved with substantially lower meat dependence. In addition, the plant-forward menu provided higher fibre content and modestly lower salt levels, potentially offering additional cardiometabolic benefits. The findings challenge the perception that meat reduction in hospital nutrition necessarily compromises protein adequacy or meal quality. Beyond nutrition, the study emphasizes the broader sustainability responsibilities of healthcare systems such as the NHS, which serve millions of meals annually and exert major influence on food procurement practices. The authors propose that environmentally conscious menu redesign can be implemented using currently available catering infrastructure without sacrificing patient nutritional standards. Although clinical outcomes and patient acceptability were not assessed, the study provides important proof-of-concept evidence supporting sustainable hospital nutrition strategies that align environmental stewardship with nutritional adequacy in modern healthcare systems.

Barriers to Prescription Therapy Persist in Chronic Idiopathic Constipation Care : Gastro Hep Advances | May 2026

Introduction Chronic idiopathic constipation (CIC) is one of the most common disorders of gut–brain interaction and is associated with substantial impairment in quality of life, healthcare utilization and economic burden. Although multiple effective prescription therapies are now available, real-world management of CIC continues to rely heavily on lifestyle modification and over-the-counter treatments. Problem Statement Despite evolving treatment options and updated clinical guidelines, limited real-world data exist regarding treatment decision-making, barriers to therapy access, patient perceptions and financial burden in CIC care. Understanding the disconnect between healthcare provider practices and patient experiences is essential for improving long-term disease management and treatment accessibility. Summary This large US real-world survey highlights important gaps between physician treatment strategies and patient experiences in chronic idiopathic constipation management. Most healthcare professionals reported following guideline-based escalation from lifestyle and dietary modification to over-the-counter agents and eventually prescription medications. However, a substantial proportion of patients who had never received prescription therapy were still considered clinically eligible for such treatment, suggesting underutilization of advanced therapies. Physicians prioritized long-term efficacy and improvement in quality of life when selecting treatment strategies, whereas patients emphasized symptom relief, affordability and treatment safety. Notably, patients frequently identified difficulty obtaining specialist appointments, limited awareness of available prescription medications and inadequate insurance coverage as major barriers to care. In contrast, physicians viewed medication cost and insurance authorization complexity as the primary prescribing obstacles. The study also demonstrated persistent reliance on lifestyle interventions despite relatively modest patient-perceived efficacy. Among prescription agents, linaclotide was generally viewed most favorably by clinicians, although overall patient satisfaction with available prescription therapies was high. Importantly, direct healthcare costs—including physician visits and medication co-payments—remained a meaningful financial burden. Overall, the study underscores that access limitations, insurance barriers and inadequate patient awareness continue to significantly influence CIC management despite the availability of effective pharmacologic therapies.

Serrated Polyposis Syndrome Requires Improved Detection and Personalized Surveillance : Endoscopy | May 2026

Introduction Serrated polyposis syndrome (SPS) is now recognized as the most common colorectal polyposis syndrome and an important precursor condition for colorectal cancer (CRC). The syndrome is characterized by multiple serrated colorectal lesions, including sessile serrated lesions and traditional serrated adenomas, which contribute substantially to colorectal carcinogenesis through the serrated neoplasia pathway. Problem Statement Despite its clinical importance, SPS remains significantly underdiagnosed because serrated lesions are frequently subtle, flat and historically misclassified during colonoscopy. In addition, uncertainty persists regarding optimal endoscopic resection techniques and long-term surveillance strategies, with most current recommendations still based on expert opinion rather than high-quality prospective evidence. Summary This review provides a contemporary overview of the evolving understanding and management of serrated polyposis syndrome, emphasizing the central role of improved endoscopic detection in reducing colorectal cancer risk. Advances in high-definition colonoscopy, chromoendoscopy, prolonged withdrawal times and refined lesion classification systems have substantially improved recognition of serrated lesions, particularly sessile serrated lesions that often present with indistinct borders and mucus caps. The review reinforces cold snare polypectomy as the preferred technique for most small nondysplastic serrated lesions because of its favorable safety profile and effective complete resection rates. For larger or dysplastic lesions, endoscopic mucosal resection remains the preferred strategy, although comparative evidence regarding cold, hot and underwater techniques specifically for serrated lesions remains limited. The article also highlights the growing shift toward individualized surveillance strategies in SPS. Although annual colonoscopy following colon clearance remains guideline standard, emerging evidence suggests that selected low-risk patients may safely undergo biennial surveillance, potentially reducing procedural burden without compromising cancer prevention. Overall, the review underscores that serrated neoplasia represents a major but still incompletely understood pathway in colorectal carcinogenesis and calls for further research to optimize detection, resection and surveillance strategies aimed at reducing interval and preventable colorectal cancers.

Persistent Diet–Microbiome–Epithelial Abnormalities Continue During Crohn’s Disease Remission : Gastroenterology | May 2026

Introduction Modern biologic therapies have significantly improved remission rates in Crohn’s disease (CD), primarily through suppression of mucosal immune activation. However, despite clinical and endoscopic remission, many patients continue to experience recurrent disease flares, suggesting that deeper pathogenic mechanisms may persist even under effective immune-targeted treatment. Problem Statement Current treatment paradigms in CD focus heavily on immune suppression, yet little is known about the residual dietary, microbial, metabolic and epithelial abnormalities that remain during remission. Understanding these persistent nonimmune perturbations may explain the relapsing nature of CD and identify adjunct therapeutic targets beyond biologic therapy alone. Summary This comprehensive multiomics study demonstrates that substantial abnormalities in diet, gut microbiota, metabolome and ileal epithelial biology persist in Crohn’s disease despite effective clinical remission and advanced biologic therapy. Patients in remission showed marked suppression of adaptive T-cell and innate granulocyte pathways, reflecting strong immune inhibition, yet simultaneously exhibited persistent activation of epithelial antibacterial pathways including DUOX2, CEACAM6 and REG family genes. Increased goblet-cell and mucin glycosylation signatures were also observed, potentially representing a compensatory epithelial response to ongoing microbial disruption. Importantly, remission was still characterized by persistent dysbiosis, reduced microbial diversity and metabolomic abnormalities similar to those observed in active disease. Dietary analysis revealed sustained unhealthy dietary patterns during remission, particularly higher intake of ultra processed foods and lower consumption of fiber, vegetables and micronutrients. Exposure to ultra processed foods correlated strongly with microbial dysbiosis and negatively correlated with genes involved in mucin glycosylation and epithelial barrier maintenance, whereas Mediterranean dietary adherence showed favorable associations. Notably, higher epithelial antibacterial and mucus-related signatures, greater dysbiosis and increased ultra processed food exposure were associated with subsequent clinical flare risk. Overall, the study supports a major conceptual shift in CD management by demonstrating that immune suppression alone may not fully normalize gut biology and that adjunctive strategies targeting the diet–epithelium–microbiome axis could be essential for achieving deeper and more durable remission states.