Trending Topics in Gastroenterology | GastroAGI

Anal High-Grade Squamous Intraepithelial Lesions (HSIL): BJS | March 2026

Introduction: Anal squamous cell carcinoma is an increasingly common but largely preventable cancer. Most cases arise from persistent high-risk human papillomavirus (HPV) infection, progressing through high-grade squamous intraepithelial lesions (HSIL). This comprehensive review summarizes the current approach to screening, diagnosis, classification, and management of anal HSIL. Why was this review needed? • The incidence of anal cancer is steadily increasing worldwide. • High-risk groups can now be clearly identified for targeted screening. • Classification and management of anal dysplasia have evolved considerably. • High-resolution anoscopy (HRA) has become the cornerstone for diagnosis and treatment. • Recent evidence supports active treatment of HSIL to prevent anal cancer. Key Takeaways: • Persistent high-risk HPV (especially HPV-16 and HPV-18) is the principal cause of anal HSIL and anal squamous cell carcinoma. • High-risk populations include people living with HIV, immunosuppressed patients, men who have sex with men, and transplant recipients. • Low-grade squamous intraepithelial lesions (LSIL) often regress spontaneously, whereas HSIL carries a substantial risk of progression and warrants treatment. • Screening high-risk individuals enables early detection and significantly reduces the risk of invasive anal cancer. • High-resolution anoscopy (HRA) is the preferred diagnostic technique, allowing accurate identification, biopsy, and treatment of precancerous lesions. • Treatment of HSIL is now recommended because it has been shown to reduce progression to invasive anal cancer. • HPV vaccination is expected to substantially reduce the future burden of anal cancer but will not eliminate disease in currently at-risk adults. • Artificial intelligence has the potential to improve HRA interpretation, increase diagnostic accuracy, and shorten the learning curve for clinicians. Clinical Impact: Anal cancer is increasingly viewed as a preventable malignancy. Targeted screening of high-risk populations, timely treatment of HSIL, wider HPV vaccination, and expanding access to high-resolution anoscopy have the potential to dramatically reduce anal cancer incidence over the coming decades. Bottom Line: Anal HSIL is a treatable precancerous condition. Early identification using high-resolution anoscopy, combined with timely treatment and HPV vaccination, represents the most effective strategy for preventing anal squamous cell carcinoma.

Post-Infection DGBI (PI-DGBI): Gut | July 2026

Introduction: Acute infectious gastroenteritis can trigger persistent gastrointestinal symptoms long after the infection has resolved, leading to post-infection disorders of gut-brain interaction (PI-DGBI). This global Rome Foundation study evaluated the prevalence, risk factors, and clinical characteristics of these disorders across 26 countries. Why was this study needed? • The global burden of PI-DGBI has not been well defined. • Risk factors for developing chronic GI symptoms after gastroenteritis remain incompletely understood. • International epidemiological data are needed to guide prevention and management. • PI-DGBI may have distinct clinical and psychological characteristics compared with other DGBIs. • Better recognition may improve long-term patient care. Results: • Approximately 1 in 10 patients with a disorder of gut-brain interaction reported a post-infectious onset, confirming acute gastroenteritis as an important trigger for chronic gastrointestinal disease. • Younger age, male sex, urban residence, anxiety, and higher somatic symptom burden were independently associated with PI-DGBI. • Patients with PI-DGBI experienced greater psychological distress and poorer physical health, with functional dyspepsia, irritable bowel syndrome, and anorectal disorders being the most common clinical presentations. Clinical Impact: This study reinforces that acute gastroenteritis is not always a self-limited illness. A significant proportion of patients develop chronic gut-brain disorders with substantial effects on quality of life. Early recognition, patient education, and multidisciplinary management—including psychological assessment when appropriate—may improve long-term outcomes. Bottom Line: Post-infection disorders of gut-brain interaction are common and clinically significant. Acute gastroenteritis can trigger long-lasting functional gastrointestinal disorders, highlighting the importance of prevention, early diagnosis, and comprehensive long-term care.

FMT in IBS: Gastroenterology | July 2026

Introduction: Gut microbiota alterations have been implicated in the pathogenesis of irritable bowel syndrome (IBS), making fecal microbiota transplantation (FMT) a promising therapeutic strategy. However, clinical trials have reported conflicting results. This updated meta-analysis evaluated the efficacy and safety of FMT in patients with IBS. Why was this study needed? • Previous FMT trials in IBS have reported inconsistent outcomes. • The role of gut microbiota modulation in IBS remains uncertain. • Larger pooled analyses are needed to clarify the true efficacy of FMT. • Variability in donor selection, FMT protocols, and patient populations has limited interpretation. • Clear evidence is required before recommending FMT in routine IBS practice. Results: • FMT did not significantly improve IBS symptoms compared with placebo in the primary intention-to-treat analysis. • Although some patients who completed treatment appeared to benefit, the overall quality of evidence was very low, with substantial variation across studies. • FMT was generally safe, with adverse events comparable to placebo, but current evidence does not support its routine use for IBS. Clinical Impact: This comprehensive meta-analysis suggests that FMT should not be routinely offered for IBS outside clinical trials. Future research should focus on identifying the patients most likely to benefit and standardizing donor selection, stool preparation, and treatment protocols. Bottom Line: Current evidence does not demonstrate a clear clinical benefit of FMT for IBS. While the procedure appears safe, its routine use cannot be recommended until higher-quality, standardized clinical trials identify the appropriate patients and optimal treatment strategies.

Laparoscopic vs Open Adhesiolysis for Bowel Obstruction: JAMA Surgery | June 2026

Introduction: Laparoscopic adhesiolysis offers several short-term advantages over open surgery for adhesive small bowel obstruction (ASBO). However, its long-term impact on recurrence, quality of life, and incisional hernia remains uncertain. The LASSO trial provides the first randomized evidence comparing these two approaches. Why was this study needed? • Long-term outcomes after laparoscopic adhesiolysis have not been well established. • Previous studies have largely focused on short-term recovery. • Whether laparoscopy reduces recurrent bowel obstruction remains unclear. • Evidence from randomized controlled trials has been lacking. • Long-term patient-centered outcomes are important when selecting the surgical approach. Results: • Recurrence of small bowel obstruction was similar after laparoscopic and open adhesiolysis over 1.5 years of follow-up. • Quality of life and incisional hernia rates did not differ between the two surgical approaches. • The study found no long-term advantage of laparoscopy over open adhesiolysis. Clinical Impact: While laparoscopy may still provide short-term benefits in carefully selected patients, surgeons should not expect improved long-term outcomes regarding recurrence, quality of life, or incisional hernia. The choice of approach should therefore be guided by patient characteristics, surgeon expertise, and intraoperative findings. Bottom Line: The LASSO trial—the first randomized study in this field—demonstrates that laparoscopic adhesiolysis offers no significant long-term advantage over open surgery for adhesive small bowel obstruction. Short-term benefits remain important, but long-term outcomes are comparable.

DPP-4 Inhibition Targets the Gut–Brain Axis in Parkinson's Disease: Gut | July 2026

Introduction: Growing evidence suggests that Parkinson's disease (PD) may originate in the gut, with pathological α-synuclein spreading to the brain through the vagus nerve. This study investigated whether sitagliptin, a widely used DPP-4 inhibitor for diabetes, could interrupt this gut–brain disease pathway. Why was this study needed? Although DPP-4 inhibitors have shown neuroprotective signals in previous studies, the underlying mechanisms remain unclear. Understanding whether these drugs can modify gut inflammation, α-synuclein propagation, and gut microbiota could open new opportunities for drug repurposing in PD. What did the study show? • Sitagliptin reduced intestinal inflammation by suppressing TLR2-mediated immune activation. • Treatment significantly decreased α-synuclein accumulation in the gut, vagus nerve, and brain. • Neuronal loss in the medulla and midbrain was reduced, with corresponding improvement in motor function. • Sitagliptin favorably altered the gut microbiome toward a profile associated with reduced PD pathology. • The neuroprotective effects persisted even after GLP-1 receptor blockade, suggesting mechanisms independent of GLP-1 signaling. • The findings identify the gut–brain axis as a potential therapeutic target for DPP-4 inhibitors. Clinical Impact: This study supports the concept of repurposing DPP-4 inhibitors as disease-modifying therapies for Parkinson's disease. By targeting gut inflammation, α-synuclein propagation, and microbiome dysbiosis, these agents may offer benefits beyond glucose control, although human clinical trials are needed. Take-Home Message: Sitagliptin attenuated gut inflammation, reduced α-synuclein spread from the gut to the brain, and improved neurological outcomes in a Parkinson's disease model. These findings highlight DPP-4 inhibitors as promising candidates for gut–brain axis–targeted therapy in Parkinson's disease.

Bedside Ultrasound Outperforms Abdominal X-Ray in Neonatal Necrotizing Enterocolitis: Frontiers in Pediatrics | July 2026

Introduction: Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal emergencies in neonates. Early identification of infants requiring surgical intervention is critical but remains challenging. This study compared bedside abdominal ultrasonography (US) with abdominal radiography (AXR) in predicting the need for surgery. Why was this study needed? Abdominal radiography has traditionally been the first-line imaging modality for NEC, but it has limited sensitivity in detecting bowel ischemia and perforation. Bedside ultrasound may provide additional information to improve surgical decision-making. What did the study show? • The study included 509 neonates with NEC, including 88 who required surgery. • Bedside ultrasound predicted the need for surgery significantly better than abdominal radiography. • Combining ultrasound with radiography further improved classification of patients at borderline risk. • Complex peritoneal fluid was the strongest ultrasound predictor of surgical intervention. • All imaging models demonstrated good calibration, supporting their clinical reliability. • Ultrasound provided valuable real-time assessment of bowel viability and intra-abdominal complications beyond conventional X-ray findings. Clinical Impact: Bedside abdominal ultrasound should be incorporated into the routine assessment of neonates with NEC, particularly when the need for surgery is uncertain. Combining ultrasound with radiography can improve risk stratification and facilitate earlier surgical consultation. Take-Home Message: Bedside abdominal ultrasound is superior to abdominal radiography in identifying neonates with NEC who require surgery. Used alongside conventional X-rays, it enhances clinical decision-making and may enable more timely surgical intervention.

Common Drugs and Clostridioides difficile Infection: Gut | July 2026

Introduction: Antibiotic exposure is the best-established risk factor for Clostridioides difficile infection (CDI). However, the contribution of many commonly prescribed non-antibiotic medications has remained uncertain. This large Swedish population-based study evaluated the association between a wide range of medications and the risk of developing CDI. Why was this study needed? As polypharmacy becomes increasingly common, especially among older adults, understanding which medications influence CDI risk is essential for preventing avoidable infections and promoting safer prescribing practices. What did the study show? • Lincosamides (particularly clindamycin) carried the highest risk of CDI, followed by broad-spectrum penicillins, cephalosporins, and trimethoprim-sulfamethoxazole. • Tetracyclines were not associated with an increased CDI risk. • Among non-antibiotic medications, antidiarrheals showed the strongest association with CDI. • Corticosteroids and proton pump inhibitors (PPIs) were independently associated with increased CDI risk. • Higher CDI risk was also observed with H2-receptor antagonists, antidepressants, nervous system drugs, constipation medications, and beta-blockers. • Lipid-lowering agents (mainly statins) and aspirin were associated with a modest reduction in CDI risk. • Nonsteroidal anti-inflammatory drugs (NSAIDs) were not associated with an increased CDI risk. Clinical Impact: Beyond antibiotic stewardship, clinicians should regularly review non-antibiotic medications that may increase CDI risk, particularly in elderly patients, hospitalized individuals, and those receiving multiple medications. Judicious use of PPIs, corticosteroids, and antidiarrheals may help reduce preventable CDI. Take-Home Message: CDI risk extends beyond antibiotics. Careful medication review—including PPIs, corticosteroids, antidiarrheals, and other commonly prescribed drugs—should become an integral part of CDI prevention, especially in patients with multiple risk factors or polypharmacy.

Seated Anorectal Manometry Better Predicts Balloon Expulsion Success: AJG |June 2026

• Dyssynergic defecation is commonly evaluated using anorectal manometry, traditionally performed in the left lateral decubitus position. • However, defecation normally occurs in the seated position, raising questions about whether conventional testing accurately reflects real-world anorectal function. • This study evaluated 384 adults undergoing high-resolution anorectal manometry and compared bear-down patterns in both lateral and seated positions. • A small but clinically important subgroup of patients demonstrated dyssynergic patterns in the lateral position that normalised when tested while seated. • Approximately 4% of patients showed normalisation of dyssynergia in the seated position. • These patients had a dramatically higher likelihood of successfully completing the balloon expulsion test (BET), one of the most important physiological markers of normal evacuation. • Normalisation in the seated position was strongly associated with successful balloon expulsion within one minute. • The findings suggest that some patients may be incorrectly classified as having dyssynergic defecation when assessed only in the traditional lateral position. • Seated testing may better reproduce physiological defecation mechanics and pelvic floor behaviour. • This has important implications for diagnostic accuracy, particularly when anorectal manometry findings and balloon expulsion test results appear discordant. • Incorporating seated assessment into routine anorectal physiology testing may improve identification of clinically relevant evacuation disorders. • The study supports a growing movement toward more physiologic testing conditions during anorectal function evaluation. Bottom line: High-resolution anorectal manometry performed in the seated position may provide a more accurate assessment of defecatory function than traditional lateral testing, with normalisation of dyssynergic patterns strongly predicting successful balloon expulsion.

DOTATATE PET in Poorly Differentiated Extrapulmonary NEC: JNM | June 2026

• Somatostatin receptor (SSTR) imaging with ⁶⁸Ga-DOTATATE PET is a cornerstone for well-differentiated neuroendocrine tumors, but its role in poorly differentiated neuroendocrine carcinoma (NEC) has remained uncertain. • Previous retrospective studies suggested that up to 40% of NECs might demonstrate strong somatostatin receptor expression, raising interest in peptide receptor radionuclide therapy (PRRT) for these patients. • This prospective study was designed to provide a more accurate assessment by evaluating an unselected cohort of metastatic extrapulmonary NEC patients. • Thirty patients with metastatic extrapulmonary NEC underwent ⁶⁸Ga-DOTATATE PET, and most also underwent ¹⁸F-FDG PET. • Primary tumor sites included pancreas, colorectum, uterus, and cancers of unknown primary origin. • Histologies included both small-cell and large-cell neuroendocrine carcinoma. • The key finding was that uniform, high-level somatostatin receptor expression was uncommon. • Only 13% of patients demonstrated strong, homogeneous DOTATATE uptake consistent with high SSTR expression. • The vast majority of tumors showed either: Absent SSTR expression Patchy/heterogeneous receptor expression Predominantly FDG-avid biology • These findings suggest that most poorly differentiated NECs retain aggressive glycolytic behavior rather than the receptor-rich phenotype typically seen in well-differentiated NETs. • The study challenges previous reports that may have overestimated SSTR positivity because of selection bias or inclusion of tumors with lower Ki-67 indices. • Clinically, this means that routine DOTATATE PET scanning is unlikely to identify large numbers of poorly differentiated NEC patients suitable for PRRT. • However, a small subset of NEC patients may still demonstrate strong receptor expression and could remain candidates for receptor-targeted therapies. • Dual-tracer imaging with FDG PET and DOTATATE PET may be particularly useful when considering individualized treatment strategies. • The findings reinforce the biological distinction between well-differentiated NETs and poorly differentiated NECs. Bottom line: Strong and uniform somatostatin receptor expression is present in only a small minority of patients with metastatic extrapulmonary poorly differentiated NEC. Most NECs remain predominantly FDG-avid tumors, limiting the routine applicability of DOTATATE-based imaging and PRRT in this population.

F. prausnitzii Counters CRC Progression : Gastroenterology | Jun 2026

Introduction: The gut microbiome plays a central role in colorectal cancer (CRC) development, influencing inflammation, metabolism, immune responses, and tumor behavior. While several microbial species have been implicated in CRC, the mechanisms through which beneficial and harmful bacteria interact with the host to promote or suppress tumor progression remain incompletely understood. Deciphering these host–microbe metabolic interactions may reveal novel biomarkers and therapeutic strategies for CRC prevention and treatment. Problem Statement: Although enterotoxigenic Bacteroides fragilis has been consistently associated with colorectal carcinogenesis, the protective mechanisms exerted by beneficial commensal organisms are less clearly defined. Understanding how microbial metabolites influence tumor biology and counteract pro-carcinogenic bacterial pathways is essential for developing microbiome-based interventions in CRC. Summary: This comprehensive multi-omics study identified a key antagonistic relationship between Faecalibacterium prausnitzii, a beneficial gut commensal, and enterotoxigenic Bacteroides fragilis in CRC. The investigators demonstrated that F. prausnitzii metabolizes dietary tryptophan into picolinic acid (PIA), a bioactive metabolite that suppresses tumor-promoting effects induced by B. fragilis. Mechanistic analyses revealed that enterotoxigenic B. fragilis enhances the expression of genes linked to aggressive tumor behavior and recurrence, whereas PIA counteracts these effects by promoting tumor cell apoptosis and downregulating these oncogenic pathways. Importantly, the findings were validated across independent patient cohorts, organoid systems, and animal models, strengthening the biological relevance of this pathway. The study further showed that a tryptophan-rich diet increased circulating PIA levels, highlighting a potential nutritional approach to modulate host–microbe interactions and reduce CRC progression. These findings define a novel microbe–metabolite–host regulatory axis, namely the F. prausnitzii–PIA pathway, as a natural defense mechanism against B. fragilis-driven carcinogenesis. The work provides compelling evidence that microbiome-targeted therapies, dietary interventions, and strategies aimed at restoring beneficial microbial communities may become important components of future CRC prevention and treatment paradigms.