Introduction

The intestinal epithelium maintains host-microbiota homeostasis, with inflammation-associated pathological shifts in intestinal epithelial cell (IEC) subtypes. RNA N6-methyladenosine (m6A) modifications have been implicated in intestinal homeostasis; however, the underlying mechanisms remain poorly understood。

Aims & Methods

This study investigates the role of m6A methyltransferase METTL3 in regulating IEC subtype dynamics and epithelial-immune crosstalk during intestinal inflammation.
Tamoxifen was administered to the transgenic mice (Mettl3^flox/floxCdx2-Cre^ERT2) to induce intestine-specific Mettl3 knockout. Dextran sodium sulfate (DSS)-induced colitis was established, with body weight, disease activity index (DAI), and colon length monitored. Single-cell RNA sequencing (scRNA-seq) of colonic epithelium, combined with m6A-seq and RNA-seq, identified METTL3-dependent epitranscriptomic and transcriptional networks. Mouse colon organoids were used for functional validation.

Results

METTL3 is enriched in intestinal stem cells and transit-amplifying cells (TACs) and upregulated in human/murine inflammatory bowel disease. Mettl3 knockout mice exhibited exacerbated DSS colitis, marked by severe weight loss, elevated DAI, and colon shortening. scRNA-seq revealed METTL3 ablation depleted epithelial lineages (TACs, goblet cells, enterocytes) while amplifying immune infiltration (macrophages, neutrophils, T cells). METTL3 loss compromised the multipotency of TACs, particularly causing a blockade in goblet cell lineage commitment. Furthermore, it boosted TNF expression and amplified the signaling from IECs to neutrophils. Mechanistically, METTL3 induced m6A modifications on Slc39a8 mRNA, thereby regulating its expression. Slc39a8 knockdown in mouse colon organoids recapitulated METTL3 deficiency in impairing self-renewal.

Conclusion

Our work establishes METTL3 as a dual guardian of intestinal homeostasis, preserving epithelial regeneration and calibrating epithelial-immune dialogue by regulating Slc39a8 expression through m6A modification.

Introduction

A small-scale study modeled the cost-effectiveness of colorectal cancer (CRC) screening, incorporating productivity factors.

Aims & Methods

Using real-world data, this research aimed to evaluate the cost-utility of Taiwan's CRC screening program, factoring in potential lifetime productivity savings. After interlinkages among databases of the Taiwan Cancer Registry, National Mortality Registry, Taiwan CRC Screening Database, and National Health Insurance claim records, we estimated lifetime survival functions for stage-specific subcohorts using a rolling extrapolation algorithm after stratified by sex and age from 2004 to 2017. We multiplied the survival rates with average utility values of EQ-5D collected from CRC cases at National Cheng Kung University Hospital, to sum up quality-adjusted life expectancy (QALE). We multiplied monthly medical costs and insured salaries by survival probabilities. We summed them over a lifetime for both the index and age-, sex-, and calendar-year matched reference subcohorts for comparison. Lifetime productivity (LP) was assessed only up to age 65. After weighing different stage distributions, we calculated the differences in total QALE loss, lifetime medical expenditures (LME), and LP between screened versus non-screened groups. Finally, we estimated the costs associated with implementing fecal immunochemical testing (FIT) in Taiwan's CRC screening program. We applied a 3% annual discount and an exchange rate of 30.58 New Taiwan Dollars per U.S. Dollar (USD) at the end of 2018.

Results

We enrolled 77,169 CRC patients aged 50–74 in the study. After weighted by different stage distribution, a screen-detected CRC case would save 2.6 (95% CI, 2.3–2.9) and 2.5 (95% CI, 2.1–2.6) QALYs for women and men, respectively, accompanied by 7,000 USD (95% CI, 4,000–10,000) and 8,000 USD (95% CI, 6,000–10,000) in LME, and 17,000 USD (95% CI, 16,000–19,000) and 23,000 USD (95% CI, 22,000–25,000) in LP. For every 100,000 persons screened, the program spent 682,000 USD for FIT, 1,051,000 USD and 1,987,000 USD for men and women, respectively, for colonoscopy, 61,000 USD and 133,000 USD for surveillance colonoscopy and 9,000 USD and 15,000 USD for treating complications. The incremental cost-utility ratio (ICUR) of 6,650 and 6,230 USD per QALY for women and men, respectively, would become 120 and -2970 USD per QALY after accounting for lifetime productivity.

Conclusion

After considering lifetime productivity, Taiwan's CRC screening program would be close to being cost-saving. Future corroboration studies are warranted.

Introduction

Polypectomy is a common endoscopic procedure with cold snare and hot snare techniques being widely used. Hot snare polypectomy involves cautery, which may increase the risk of thermal injury and related complications. Cold snare polypectomy has a well-established safety and efficacy profile for small colonic polyps, however, comparative data on the clinical outcomes of these two methods for gastric polyps remains limited.

Aims & Methods

A retrospective analysis was conducted on 161 consecutive gastric polypectomies for polyps under 10mm, comprising a sample of 41 patients that underwent cold snare polypectomy and 120 patients that underwent hot polypectomy over a period of 5 years.

Results

The mean polyp size differed significantly between groups, being smaller in the cold snare group (5.20 ± 1.18 mm vs 6.34 ± 1.49 mm; p < 0.001). The Charlson Comorbidity Index averaged 3 points, with no significant differences between the groups regarding the use of anticoagulant or antiplatelet therapy. Statistically significant differences were observed in both the location and histological type of the polyps between the two techniques (p = 0.003 ; p < 0.001). Cold snare polypectomy was more frequently used for polyps located in the fundus and for fundic gland polyps, whereas hot snare polypectomy was more commonly utilized for polyps located in the cardia and antrum. Submucosal injection with gelofusine and adrenaline were more frequently associated with the hot snare technique (p = 0.001). Regarding clinical outcomes, intra-procedural bleeding occurred in 16.1% of cases and was successfully managed endoscopically in all instances, mainly with clips (76.9%). No cases of delayed bleeding or perforation were observed. There were no significant differences between the groups concerning complete histological resection or polyp recurrence.

Conclusion

Cold snare polypectomy demonstrated comparable safety and efficacy to hot snare polypectomy in the resection of small gastric polyps, possibly representing a preferable approach to avoid thermal injury and related complications.

Introduction

Colonoscopy is the gold standard investigation in the lower gastrointestinal tract. However, 75% of patients can experience pain or discomfort with moderate sedation. The application of robotic technology promises to advance and overcome difficulties faced including better utilisation of rooms for advanced procedures and to achieve a complete colonoscopy in patients where pain and technical challenges inhibit progression.

Aims & Methods

This pilot study, the first at a UK NHS Hospital between January 2023 to April 2025 with an expert endoscopist performing the robotic colonoscopy with the Endotics system. This is a disposable soft robot which employs expand and contract movement to self-propel along the bowel. Patients with failed previous standard colonoscopy along with index diagnostic procedures deemed potentially difficult were recruited. Procedures were performed outside the endoscopy unit similar to an outpatient clinical room.

Results

112 patients were recruited (50M:62F), mean-age 56.3 years over 27 months. The commonest indications for robotic colonoscopy were rectal bleeding (36.9%), failed standard colonoscopy (22.6%) and change in bowel habit (17.2%). 23 patients had failed previous standard colonoscopy with 16 patients achieving completion with subsequent robotic colonoscopy (70% improvement). Average caecal intubation time 36.63 minutes with average total procedure time 48.74 minutes.

Conclusion

Robotic colonoscopy provides a safe and effective method in improving comfort and completion-rates, including previously failed colonoscopy. Direct visualisation, biopsy and polypectomy is still possible with robotic colonoscopy. This study has demonstrated a viable alternative to conventional colonoscopy. With no sedation it allows procedures to be conducted outside the traditional endoscopy unit such as outpatients. The study highlights a learning curve to reduce caecal intubation time. The study is expanding with further endoscopists being trained in robotic endoscopy with a view to expand the service available to patients.

Introduction

Lynch syndrome is a hereditary cancer predisposition syndrome associated with a significantly increased risk of colorectal cancer (CRC). Despite regular colonoscopic surveillance, patients remain at considerable risk of developing CRC. Surgical resection has long been the cornerstone of curative treatment, but it often comes with substantial morbidity. Endoscopic en-bloc resection techniques such as endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (eFTR) may offer effective, organ-sparing alternatives for early invasive cancers, but data on their safety and oncological outcomes in Lynch syndrome patients are lacking.

Aims & Methods

We conducted a multicenter, multinational retrospective case series including Lynch syndrome patients with confirmed pathogenic variants in MLH1, MSH2, MSH6, PMS2, or EPCAM deletions who underwent endoscopic en-bloc resection for malignant colorectal lesions between 2010 and 2024. Clinical, procedural, histological, and follow-up data were collected from medical records. The primary outcome was the rate of curative endoscopic resection, defined as radical resection without the need for surgery and no locoregional recurrence or distant metastasis at 6 months. Secondary outcomes included locoregional recurrence or distant metastasis at 24 and 60 months, along with the number of additional resections performed.

Results

A total of 38 patients (mean age 61.3 ± 15 years, 50% female) underwent 17 ESDs, 19 eFTRs, 1 endoscopic intermuscular dissection (EID), and 1 hybrid procedure (Combined ESD + eFTR). The R0 resection rate was 89% (34/38). Thirteen (34%) patients underwent additional surgery, with 12 cases due to T1CRC with high risk features (including all 4 cases with R1 resection) and 1 case due to perforation. In 25 patients (66%), curative treatment was achieved through endoscopic resection alone. Of these, 18 completed at least 6-months of follow-up, all of whom were disease-free. At 24 months, endoscopy was performed in nine patients, all of whom remained disease-free. Two patients completed 60-months of follow-up with no recurrences.

Conclusion

This is the first and largest case series of patients with Lynch syndrome treated with en bloc endoscopic resection. In 7 out of 10 patients, curative treatment was achieved through endoscopic resection alone without exposing patients to the morbidity of oncological surgery. These findings suggest that ESD and eFTR are safe and could serve as minimally invasive alternatives to surgery for selected patients, warranting further prospective evaluation.

Introduction

Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by disrupted interactions between the gut microbiota and the host immune system, notably associated with the depletion of spermidine-producing Blautia species. Here, we investigated whether restoring this microbial–metabolite axis could rebalance intestinal immunity via spermidine-driven signaling pathways in regulatory B cells (Bregs).

Aims & Methods

We assessed the therapeutic potential of live Blautia coccoides in a dextran sulfate sodium (DSS)-induced colitis mouse model, comparing it to treatments with heat-killed Blautia, exogenous spermidine, and a spermidine synthesis-deficient Blautia mutant (ΔSPDS). Daily oral treatments were initiated during colitis induction. Disease progression was evaluated using clinical scoring, histopathological analysis, and intestinal permeability assays. Spermidine levels in fecal and tissue samples were quantified, while Breg populations and STAT3 activation were analyzed by flow cytometry and phospho-specific staining. To explore clinical relevance, we performed spatial transcriptomics on UC patient biopsies and ex vivo stimulation of PBMCs from anti-TNF-refractory UC patients with Blautia-derived metabolites.

Results

Live Blautia treatment significantly improved both clinical and histological outcomes, including reduced mucosal ulceration, decreased inflammatory infiltration, and restored expression of tight junction proteins. In contrast, heat-killed bacteria provided no therapeutic benefit. Intestinal permeability assays confirmed the recovery of barrier integrity following Blautia or spermidine administration, an effect absent in ΔSPDS-treated mice. Early in treatment, local spermidine levels were restored, coinciding with a progressive expansion of IL-10-producing Bregs exhibiting robust STAT3 phosphorylation. These immunological responses were absent in both ΔSPDS-treated and STAT3-deficient mice. Cytokine profiling revealed a shift toward an anti-inflammatory environment, with decreased TNF-α and IL-6 and elevated IL-10 levels in colonic tissues. Spatial transcriptomics identified microanatomical niches where Blautia co-localized with STAT3-activated Bregs and increased IL-10 transcripts. Furthermore, ex vivo stimulation of PBMCs from refractory UC patients with Blautia metabolites promoted Breg differentiation and restored their ability to suppress TNF-α release, reinforcing the role of microbial-derived metabolites in regulating immune homeostasis.

Conclusion

Our findings establish Blautia as a critical regulator of intestinal immunity, acting through a spermidine–STAT3–Breg axis to repair immune–epithelial dysfunction in UC. This comprehensive validation—from bacterial genetics and animal models to human tissue analyses—supports the development of targeted probiotic or precision microbiota-based therapies aimed at replenishing spermidine-producing Blautia in patients with refractory UC.

References

1. Solitano V, et al. Shaping the future of inflammatory bowel disease: a global research agenda for better management and public health response. Nat Rev Gastroenterol Hepatol. 2025 Apr 22.
2. Guo X, et al. Gut microbiota and epigenetic inheritance: implications for the development of IBD. Gut Microbes. 2025 Dec;17(1):2490207.
3. Guggeis MA,et al. Microbiota-derived metabolites in inflammatory bowel disease. Semin Immunopathol. 2025 Mar 4;47(1):19.
4. Sun M, et al. Regulatory immune cells in regulation of intestinal inflammatory response to microbiota. Mucosal Immunol. 2015 Sep;8(5):969-978.
5. Taylor H, et al. Autoimmunity in inflammatory bowel disease: a holobiont perspective. Curr Opin Immunol. 2025 Apr 18;94:102557.
6. Maerz JK, et al.. Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses. Front Immunol.2020 Jan 24;10:3093.

Introduction

A well-established association exists between dietary fibre intake and overall health, with fibre recognised as a therapeutic intervention for a number of gastrointestinal disorders, including irritable bowel syndrome and chronic constipation.^1,2 A diet rich in dietary fibre is endorsed by guidance from United European Gastroenterology and the European Society of Clinical Nutrition and Metabolism, however only 9% of the UK population consumes the recommended amount of 30g/day of fibre.^3-5
Providing patients with clear and specific dietary recommendations is likely to enhance compliance, leading to improved health outcomes.⁶ While doctors often provide generalised advice to patients to increase their fibre intake, little is known about their specific or detailed knowledge of fibre-rich foods and the methods they use to counsel patients on dietary modifications.

Aims & Methods

This study aimed to assess how well doctors identified food as high fibre sources, their confidence in providing fibre-related advice, and how frequently they engage in such discussions.
A cross-sectional survey targeting hospital doctors in the UK was conducted via a questionnaire in April 2025 using the Qualtrics platform. The survey captured demographic data, clinical practices, knowledge, and confidence levels in fibre-related counselling. All responses were anonymous. Participants were asked to rate the amount of dietary fibre in a representative selection of 8 foods from different food categories. Food was classified as high fibre (≥6g/100g), medium fibre (3-5g/100g), and low/no fibre food (<3g/100g). All nutritional information was obtained from the British Nutrition Foundation.⁷

Results

Seventy-one responses were collected, 1 was incomplete, leaving 70 for analysis. Most doctors worked in either gastrointestinal surgery (46%) or internal medical (41%) specialties. The largest group of respondents stated that they were required to provide dietary advice to patients at least each week (49%).
Many respondents could not identify that high fibre food sources such as bran flakes (49%) and wholemeal toast (56%) had more than 6g/100g of fibre. Some respondents also wrongly classified low/no fibre food to be high fibre sources (apple [30%], banana [29%], and salads [40%]). No respondent was able to correctly identify the correct fibre category for all 8 foods.
Sixty percent of respondents stated a lack of confidence in providing dietary advice regarding fibre intake to patients and 61% did not feel confident in altering a patient’s daily fibre intake based on their clinical condition.

Conclusion

Many doctors cannot accurately categorise food which are high, medium and low/no fibre food sources. Most doctors do not feel confident in providing fibre advice to patients. This is likely to impact patient understanding and successful adherence to fibre rich diets. Easily accessible resources and dedicated teaching on fibre intake should be provided to doctors in allied specialties as this has the potential to improve patient care.

References

1. Barber TM, Kabisch S, Pfeiffer AFH, Weickert MO. The Health Benefits of Dietary Fibre. Nutrients [Internet]. 2020 Oct 21;12(10):3209. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7589116/
2. Yang J. Effect of dietary fiber on constipation: A meta-analysis. World Journal of Gastroenterology [Internet]. 2012;18(48):7378. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544045/
3. Food and Drink Federation . Action on Fibre [Internet]. The Food & Drink Federation. 2022 [cited 2025 Apr 25]. Available from: https://www.fdf.org.uk/fdf/our-work/our-campaigns/action-on-fibre/
4. Hooper B, Spiro A, Stanner S. 30 g of Fibre a day: an Achievable recommendation? Nutrition Bulletin [Internet]. 2015 May 19;40(2):118–29. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/nbu.12141
5. Gressier M, Frost G. Minor Changes in Fibre Intake in the UK Population between 2008/2009 and 2016/2017. European Journal of Clinical Nutrition [Internet]. 2021 May 13;76(2). Available from: https://www.nature.com/articles/s41430-021-00933-2
6. McKeown NM, Fahey GC, Slavin J, van der Kamp JW. Fibre Intake for Optimal health: How Can Healthcare Professionals Support People to Reach Dietary recommendations? BMJ [Internet]. 2022 Jul 20;378:e054370. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298262/
7. BRITISH NUTRITION FOUNDATION. Fibre - Nutrition Information - British Nutrition Foundation [Internet]. British Nutrition Foundation. 2023. Available from: https://www.nutrition.org.uk/nutritional-information/fibre/