Gastroduodenal

Outcome of a FODMAP restriction diet with subsequent blinded reintroduction in functional dyspepsia/postprandial distress syndrome

Van den Houte K, Broeders B, Tóth J, et al. Outcome of a FODMAP restriction diet with subsequent blinded reintroduction in functional dyspepsia/postprandial distress syndrome. Gut 2025; 75(1): 57-64. doi: 10.1136/gutjnl-2024-334156.

Functional dyspepsia (FD) is a common disorder of a likely heterogeneous aetiology. Previous studies have shown two FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), fructans and fructose, can interfere with gastric accommodation. In addition, prior studies demonstrate low-grade immune activation and increased duodenal permeability may be associated with altered enteric function, motility and symptoms as potential mechanisms for FD.

Van den Houte et al. conducted a prospective mechanistic study. Thirty-six patients with FD (33% overlap with irritable bowel syndrome (IBS)) completed a 6-week strict low-FODMAP intervention. Duodenal biopsies to assess mucosal permeability were obtained at baseline and at 6 weeks. Patients who responded underwent blind and randomised reintroduction of individual FODMAPs.

73% of patients achieved significant improvement in symptoms, with reductions in early satiety, postprandial fullness and bloating. Symptom improvement occurred rapidly (within 2 weeks). Quality of life (SF-NDI, Short-Form Nepean Dyspepsia Index), global upper GI symptoms (PAGI-SYM, Patient Assessment of Upper Gastrointestinal Disorders Symptoms Questionnaire), somatisation (PHQ-15, Patient Health Questionnaire - 15-item), and depression scores (PHQ-9, Patient Health Questionnaire-9) also improved significantly. Treatment response was independent of IBS overlap, supporting the use of dietary therapy in FD on its own merit. No significant difference in duodenal mucosal permeability (transepithelial resistance and dextran flux) pre- and post- diet was observed.

Blinded reintroduction in 27 patients revealed a significant increase in symptoms. Mannitol was the most common trigger (23%), followed by fructans, GOS (galacto-oligosaccharides), fructose and sorbitol (~15%). 27% of patients developed symptom recurrence with glucose (control substance), challenging assumptions regarding its neutrality in FD and suggesting altered proximal nutrient sensing.

A low-FODMAP diet could represent a valuable non-pharmacologic option in the FD armamentarium. Further studies are required to determine mechanisms.

Colon

Support cells in the tumour microvasculature promote colorectal cancer metastasis

Wang S, Ye G, Xu X, et al. Pericyte drives the formation of circulating tumour cell-neutrophil clusters to promote colorectal cancer metastasis. Gut 2026; 75(1): 81–93. doi: 10.1136/gutjnl-2024-334618.

Metastasis remains the major cause of death in colorectal cancer (CRC), yet effective strategies to prevent it are lacking. One increasingly recognised driver of metastatic spread is the formation of circulating tumour cell (CTC)–neutrophil clusters in the bloodstream. These clusters enable tumour cells to evade immune attack and seed distant organs more efficiently than single tumour cells. However, where these clusters form and how they are regulated has remained unclear.

In this study, Wang et al. show that CTC–neutrophil clusters form within the blood vessels of primary CRC tumours and that specialised cells supporting tumour blood vessels, known as pericytes, play a central role in this process. Using human tumour samples alongside advanced mouse models and intravital imaging, Wang et al. demonstrate that clusters arise at a “vascular–immune interface”, where tumour cells enter the circulation and interact with neutrophils adherent to inflamed endothelium. Importantly, a higher number of these intravascular clusters was associated with poorer survival and an increased risk of liver metastasis.

The study identifies a subgroup of tumour pericytes with high expression of nicotinamide N-methyltransferase (NNMT), an enzyme involved in cellular metabolism. Tumours enriched with NNMT-positive pericytes showed greater endothelial inflammation, increased neutrophil recruitment and enhanced CTC–neutrophil clustering. 

Notably, genetic or pharmacological inhibition of NNMT specifically in pericytes reduced CTC–neutrophil clusters and suppressed liver metastasis in mouse models. Clinically, a high proportion of NNMT-positive pericyte-covered tumour vessels predicted worse outcomes across CRC stages.

Overall, this work highlights the tumour vasculature as an active driver of metastasis rather than a passive conduit, suggesting pericyte signalling as a potential therapeutic target in CRC.

Neurogastroenterology

Global prevalence and gastrointestinal symptom burden after cholecystectomy

Konings B, Balsiger L, Hreinsson J, et al. Global prevalence and gastrointestinal symptom burden of individuals with a history of cholecystectomy. Gut 2026; 75: 65–71. doi:10.1136/gutjnl-2024-334531

Cholecystectomy is one of the most commonly performed surgical procedures worldwide and is traditionally considered curative for symptomatic gallstone disease. However, many patients report persistent or new gastrointestinal symptoms after surgery, often compatible with disorders of gut–brain interaction (DGBI). Despite this, the global prevalence of cholecystectomy and its association with chronic GI symptom burden have not been well characterised.

Konings et al. performed a large, population-based cross-sectional analysis using data from the Rome Foundation Global Epidemiology Study, including 54,127 participants across 26 countries. Participants self-reported a history of cholecystectomy and completed validated Rome IV questionnaires to assess symptoms compatible with DGBI throughout the gastrointestinal tract. Logistic regression models were used to compare symptom prevalence between individuals with and without cholecystectomy, adjusting for demographic and psychological confounders.

The global prevalence of a history of cholecystectomy was 5.0%, with marked geographic variation, ranging from 1.9% in Asia to 9.9% in North America. Individuals with prior cholecystectomy were significantly more likely to meet diagnostic criteria for any DGBI, with particularly strong associations for gastroduodenal, anorectal, oesophageal, and bowel disorders. Symptoms such as diarrhoea, faecal urgency, bloating, abdominal pain, and faecal incontinence were notably more frequent and severe in the cholecystectomy group. These individuals also reported greater medication use and as a result, higher healthcare utilisation. 

Although causality cannot be inferred from this cross-sectional design, this study highlights a substantial and under-recognised symptom burden following cholecystectomy. These findings support the need for improved patient selection, better preoperative recognition of DGBI, and more comprehensive postoperative counselling regarding the long-term gastrointestinal effects of cholecystectomy.

Pancreas

Glycaemic control is a modifiable risk factor for pancreatic cancer development in patients with diabetes: a population-based cohort study

Tan J, Mao X, Lui D, et al. Glycaemic control is a modifiable risk factor for pancreatic cancer development in patients with diabetes: a population-based cohort study. Gut 2025; 75(1): 94-104. doi: 10.1136/gutjnl-2025-335837.

Pancreatic cancer (PC) carries a very poor prognosis, largely due to late symptom onset, the absence of effective early detection strategies, and limited surgical eligibility at diagnosis. Preventive strategies have therefore attracted considerable interest, particularly optimal glycaemic control in patients with diabetes, given the approximately two-fold increased risk of PC in this population. However, existing research in this area has been limited, often constrained by confounding factors, inadequate statistical power, and insufficient consideration of reverse causality.

Tan et al. investigated the association between glycaemic control and PC development in patients with type 2 diabetes (T2D) using a retrospective cohort design including 458,311 individuals from Hong Kong. To address inconsistencies in prior studies, Tan et al. applied strict inclusion criteria, enrolling only patients with T2D of at least three years’ duration (to minimise reverse causality related to new-onset diabetes, as recommended by the European Society for Medical Oncology) who were receiving antidiabetic medication and monitoring. Patients with suspected type 1 diabetes, prior PC, immunoglobulin G4–related disease, or a history of pancreatectomy were excluded.

Over a median follow-up of 10 years, optimal glycaemic control (defined as a time-weighted HbA1c (haemoglobin A1C) < 7%) was associated with a 57% reduction in PC incidence and a 65% reduction in PC-related mortality compared with suboptimal control. This protective association was consistent across subgroups defined by age, sex, body mass index, comorbidities, diabetes severity, and medication use, with attenuation observed only among statin and insulin users.

Combined control of HbA1c and fasting glucose was associated with the lowest PC risk and may therefore represent an additional onco-preventive strategy in patients with T2D. Further prospective multicentre studies are warranted to confirm these findings and establish this PC preventative strategy.

IBD

Smoking affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota

Miyauchi E, Taida T, Uchiyama K, et al. Smoking affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota. Gut 2026; 75: 46-56. doi: 10.1136/gutjnl-2025-334922.

Cigarette smoking is a well-established environmental modifier of inflammatory bowel disease (IBD), known to increase the risk of flares in Crohn’s disease (CD) while paradoxically conferring protection in ulcerative colitis (UC). The biological mechanisms driving these divergent effects remain unclear. In this study, Miyauchi et al. hypothesised that smoking differentially influences UC and CD pathogenesis through alterations in the gut microbiome.

The microbiota of faecal, intestinal lavage, and saliva samples from UC and CD patients who were current smokers, ex-smokers, or never-smokers was profiled using 16S ribosomal RNA (rRNA) sequencing and gas chromatography–tandem mass spectrometry. Active smoking in UC was associated with increased faecal concentrations of short-chain fatty acids and aromatic compounds, as well as enrichment of oral commensals such as Streptococcus and Haemophilus, indicating ectopic colonisation of the colonic mucosa.

Mechanistic experiments demonstrated that aromatic compounds, including hydroquinone, promoted the growth of oral commensals in vitro. In mice, oral administration of hydroquinone altered luminal and mucosal microbiota composition and enhanced colonic mucosal colonisation by gavaged Streptococcus, suggesting that smoking-associated metabolites facilitate oral bacterial translocation into the colon in UC. Oral bacterial strains enriched in smokers were then administered to germ-free mice, with Streptococcus mitis demonstrating induction of colonic Th1 (T helper 1 cell) and IFN-γ-producing (interferon gamma) CD8 (cluster of differentiation) T cells. Notably, S. mitis administration ameliorated oxazolone-induced colitis, a Th2 (T helper 2 cell)-mediated model of UC, while exacerbating TNBS (trinitrobenzene sulfonic acid)-induced colitis, a Th1-mediated model of CD. 

Collectively, these data suggest that smoking-associated gut metabolites promote ectopic colonisation by oral commensals which drive Th1-skewed colonic immune responses, providing a mechanistic explanation for the divergent effects of smoking in UC and CD.

Endoscopy

Endoscopic or surgical gastroenterostomy for malignant gastric outlet obstruction: a randomised trial

Bang J, Puri R, Lakhtakia S, et al. Endoscopic or surgical gastroenterostomy for malignant gastric outlet obstruction: a randomised trial. Gut 2026; 75: 24-32. doi: 10.1136/gutjnl-2025-336339.

Pancreatobiliary, gastric and duodenal neoplasia can all contribute towards malignant gastric outlet obstruction (GOO), which in turn can lead to nausea, vomiting, poor nutritional status and subsequent consequences on the effectiveness of oncological treatment. Surgical gastrojejunostomy (SGJ) has been the traditional form of treatment, but the emergence of Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has resulted in a less invasive method. This randomised multicentre (USA, Germany and India) superiority trial aimed to establish whether EUS-GE has clinical and health economic benefit over SGJ.

Seventy-four patients with symptomatic malignant GOO were randomised to receive either EUS-GE (n=38) or SGJ (n=36). The primary endpoint was a composite of oral nutritional intake post intervention (using a clinical score), need for reintervention or supplemental nutrition, or procedure related adverse events over six months or until death. EUS-GE significantly outperformed SGJ for the primary outcome, with a lower incidence of composite failure (7.9% vs. 38.9%; risk difference –31.0%, p=0.002). 

Other clinical benefits of EUS-GE demonstrated during the study include quicker progression to a solid diet (median 2 vs. 5 days), reduced hospital stay (median 3 vs. 9 days), improved health-related quality of life, and lower treatment costs (mean approximately US$34,000 vs. US$51,000).

This study demonstrates EUS-GE achieves safe and effective palliation for gastric outlet obstruction but better recovery, patient experience and efficiency in comparison to SGJ, and would suggest EUS-GE should be adopted as the preferred palliative intervention for malignant gastric outlet obstruction.

Reviewers

• Dr Anahita Sharma, ST6 Gastroenterology Registrar, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK
• Dr Mirashini Swaminathan, Gastroenterology Specialist Registrar, NHS University Hospitals of Liverpool Group, Liverpool, UK
• Dr Daniela Toumazi, CT2 Internal Medicine Trainee, Broomfield Hospital, Mid and South Essex NHS Trust, Chelmsford, UK
• Dr David Gomez, ST4 Gastroenterology, Royal Free London NHS Foundation Trust, London, UK
• Dr John P Thomas, Chain-Florey Clinical Research Fellow, MRC Laboratory of Medical Sciences & Imperial College London, London, UK
• Dr Vinoth Nadesalingam, Consultant Gastroenterologist, Bart’s Health NHS Trust, London, UK

BSG GUT Highlights is edited by Dr Philip J Smith, Honorary Consultant Luminal Gastroenterologist, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Mount Vernon, Liverpool, UK. Dr Smith is the Digital and Education Editor of GUT, Editor in chief of Frontline Gastroenterology and Associate Editor of BMJ Open Gastroenterology.

Funding

The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests: None declared.

Provenance and peer review: Not commissioned; internally peer reviewed.