Gut最新文献

{"title":"Gastrointestinal microbiota and inflammasomes interplay in health and disease: a gut feeling","authors":"Roberto De Luca, Valentina Arrè, Stefano Nardone, Sandra Incerpi, Gianluigi Giannelli, Pankaj Trivedi, Eleni Anastasiadou, Roberto Negro","doi":"10.1136/gutjnl-2025-334938","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334938","url":null,"abstract":"The intricate interplay between the gut microbiota and the GI tract has garnered significant attention, as growing evidence has identified the inflammasome as a crucial yet underexplored master regulator in microbiota-driven diseases. Triggered by a variety of dangers, inflammasomes are supramolecular complexes that regulate immune response. A large number of bacterial-derived inducers have been characterised so far. Although structurally divergent, threats are neutralised by the inflammasome, which is then classified into three families: (1) nucleotide-binding oligomerisation domain, leucine-rich repeat-containing proteins, (2) absent in melanoma 2-like receptors and (3) pyrin. An unbalanced microbiota composition, expressed by a dysbiotic phenotype, might therefore induce undesired inflammasome activation, altering the local host homeostasis. Recent studies on the ‘microbiota-inflammasome axis’ have uncovered unexpected roles for inflammasome signalling in various types of GI cancer and IBD. Additionally, beyond local gut functions, microbiota influences stress responses and neurological health through aberrant secretion of inflammasome-processed cytokines, linking gut-derived signals to systemic diseases via the vagus nerve and the hypothalamic-pituitary-adrenal axis. Besides the standard experimental approaches, this complex network of interactions is now being addressed by Artificial intelligence, which emphasises the profound impact of the gut microbiota on GI health, cancer progression and brain function, opening new avenues for therapeutic intervention in GI diseases, cancer and neurological disorders. Ultimately, microbiota-inflammasome interactions manage a regulatory framework that influences inflammation, cancer progression and systemic diseases, positioning it as both a mediator and a promising therapeutic target in GI malignancies and systemic diseases of the central nervous system.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"58 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A black liver","authors":"Huang Xing","doi":"10.1136/gutjnl-2025-335607","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335607","url":null,"abstract":"A 72-year-old man diagnosed with rectal adenocarcinoma underwent laparoscopic radical resection with prophylactic loop ileostomy in our department. Following the surgery, the patient completed four cycles of adjuvant chemotherapy with the XELOX regimen (capecitabine plus oxaliplatin) in accordance with the current treatment guidelines. During the scheduled stoma reversal procedure, intraoperative exploration revealed an unexpected finding of black discolouration of the liver surface (figure 1). Figure 1 During the scheduled stoma reversal procedure, intraoperative exploration reveals an unexpected finding of black discolouration of the liver surface. What is the most likely diagnosis? For further assessment, a screenshot of the liver from the video recording of the previous surgery was retrieved for comparison (figure 2A). In addition to …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"50 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway","authors":"BMJ Publishing Group Ltd and British Society of Gastroenterology","doi":"10.1136/gutjnl-2017-313778corr1","DOIUrl":"https://doi.org/10.1136/gutjnl-2017-313778corr1","url":null,"abstract":"Li M, Xu C, Shi J, et al . et al Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway. Gut 2018;67:2169–80. This article has …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"19 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commensal Bacteroides T6SS alleviate GI-aGVHD via mediating gut microbiota composition and bile acids metabolism","authors":"Pengfei Li, Qiyi Lei, Xinghao Yu, Ying Shen, Yiyin Chen, Chang Hou, Bo Hu, Yanfang Cui, Zhihua Liu, Yi Qin, Haiyan Liu, Dandan Lin, Yang Xu, Depei Wu","doi":"10.1136/gutjnl-2024-334565","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334565","url":null,"abstract":"Background Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is one of the main complications of patients undergoing allogenic haematopoietic stem cell transplantation (allo-HSCT). A deeper understanding of the mechanisms of sustaining intestinal homeostasis is essential. Objective Here, we investigated micro-organisms and microbial metabolites that were crucial for intestinal homeostasis in the context of GI-aGVHD management. Design We profiled the gut microbiota, immune indices and gut metabolism of 71 patients undergoing allo-HSCT. Initially, we set up a mouse aGVHD model to confirm the effect of Bacteroides fragilis type VI secretion system (T6SS) on aGVHD progression. Subsequently, we applied 16S amplicon sequencing and metabolic profiling to reveal the function of B. fragilis T6SS on microbial structure intestinal and metabolome. Finally, the mediation package was used to validate our findings in clinical samples. Results A higher abundance of Bacteroides spp contributes to reducing the incidence of GI-aGVHD, and the T6SS is required for Bacteroides spp protection on aGVHD. T6SS-mediated antagonism regulates the structure and composition of gut microbiota, affecting the entire gut metabolome, particularly the bile acids metabolism, subsequently reducing inflammation response in the intestine and protecting intestinal barrier integrity. Notably, accumulating primary bile acids such as chenodeoxycholic acid exacerbated aGVHD by enhancing the activation of T cells. Mediation analysis further validated that T6SS affects the incidence of GI-aGVHD through its effect on primary bile acid metabolism. Conclusions T6SS in commensal bacteria could modulate bile acid metabolism, potentially impacting aGVHD outcomes and offering a novel target for therapeutic interventions. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"347 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the definition of gastro-oesophageal junctional zone: an immunohistochemical study using resected mucosal specimens","authors":"Kazuhiro Ota, Ken-ichi Mukaisho, Yuto Shimamura, Tetsuo Ushiku, Mitsuaki Ishida, Shun Sasaki, Taro Iwatsubo, Noriaki Sugawara, Akitoshi Hakoda, Hiroki Nishikawa, Kazuhide Higuchi, Mitsuhiro Fujishiro, Takuji Gotoda, Michio Kaminishi, Kentaro Sugano","doi":"10.1136/gutjnl-2025-335666","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335666","url":null,"abstract":"In 2022, the gastro-oesophageal junctional zone (GOJZ) was proposed at the International Consensus Conference in Kyoto as the area extending 1 cm proximally and 1 cm distally from the gastro-oesophageal junction (GOJ), defined by the distal end of the palisade vessels (DEPV).1 2 The definition of GOJ remains a matter of debate. In the globally recognised GOJ cancer classification, a Siewert type II tumour is an adenocarcinoma located 1 cm above to 2 cm below the GOJ, representing a ‘true carcinoma of the cardia’.3 Although the distribution of cardiac glands should determine GOJZ, distinction between native cardiac glands and metaplastic changes at the GOJZ remains a histological challenge due to conventional H&E staining limitations. The previous studies failed to differentiate between pyloric/pseudopyloric metaplasia and cardiac or oxyntocardiac glands, as they did not use immunohistochemical stainings of pepsinogen I (PPGI). This was a single-centre retrospective study that analysed GOJ mucosal specimens that had been resected via endoscopic submucosal dissection for treating refractory gastro-oesophageal reflux disease (GORD) (online supplemental material 1).4 Only those cases where the palisade vessel was identifiable in more than half of the specimens were included, resulting in an analysis of 11 cases comprising 120 slices from 51 patients who underwent endoscopic mucosal resection. Mucosal specimens containing the GOJZ were analysed to identify cardiac glands, parietal cells, and chief cells or pyloric/pseudopyloric metaplastic glands, using immunohistochemical staining for MUC6, H+/K+-ATPase and PPGI (online supplemental material 2). The distances from the DEPV to the proximal and distal edges of the cardiac glands, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"56 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin lesions and chest pain in a patient with Crohn’s disease","authors":"Ouwais Alkhateb, Racha Ftouni, Ossama Abbas, Fadi H Mourad","doi":"10.1136/gutjnl-2025-335547","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335547","url":null,"abstract":"A male patient aged 28 years with an 8-year history of ileal Crohn’s disease was started on combination therapy with infliximab and azathioprine 12 months ago. He was maintained on infliximab at a dose of 5 mg/kg administered every 8 weeks, and achieved sustained clinical remission. After receiving his sixth dose of infliximab, the patient developed intensely pruritic, erythematous papules and pustules on the palms and soles, associated with desquamation (figure 1A,B). This was followed by acneiform eruptions on the back (figure 1C), and subsequently, similar lesions appeared on the face, scalp and postauricular areas. Concurrently, he reported acute-onset, rapidly progressing chest pain predominantly localised to the sternoclavicular and sternocostal joints. Physical examination revealed marked tenderness over the costochondral joints. A comprehensive cardiac workup—including ECG, serum troponin levels and stress echocardiography—was unremarkable. However, chest MRI demonstrated bone marrow oedema at …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"78 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rare cause of long-segment colitis","authors":"Tien Yew Chern, Saiumaeswar Yogakanthi, William Chiang, Mustafa Mohamedrashed, Sophie Hale, Basil D’Souza, Neil Strugnell, Mayur Garg","doi":"10.1136/gutjnl-2025-335552","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335552","url":null,"abstract":"A 65-year-old previously well man presented with 3 weeks of generalised abdominal pain and diarrhoea up to three times per day after overseas travel. White cell count (9.6×106/L) and C-reactive protein (196 mg/L) were raised; however, comprehensive stool testing was negative for viral, bacterial and parasitic causes. Faecal calprotectin was <5 µg/g. CT demonstrated a long segment of circumferential bowel wall thickening and oedema from the rectosigmoid to the splenic flexure with normal enhancement of the mesenteric arteries (figure 1). Figure 1 Radiological, endoscopic and histological findings. (A) CT showing diffusely thickened rectosigmoid and descending colon with associated mesenteric stranding. (B) Endoscopic view of the sigmoid colon with pale, oedematous and friable mucosa with telangiectasia. (C) The histology showed marked myointimal hyperplasia of the submucosal veins. The lack of an internal elastic lamina …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"33 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: ‘Perspective on enhancing CRC risk prediction’ by Zheng and Wang","authors":"Craig Mowat","doi":"10.1136/gutjnl-2025-335774","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335774","url":null,"abstract":"We are very grateful for the interest in our paper on improving colorectal cancer (CRC) risk prediction in symptomatic patients attending primary care1 expressed by Doctors Zheng and Wang,2 and they highlight some interesting points which we address in the Discussion. To date, the generalisability of Faecal Immunochemical Test (FIT)-based research conducted on a specific FIT analyser has been questioned because the stool collection devices used by analyser manufacturers are not standardised and contain different buffer fluid/antibodies which …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"55 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold snare endoscopic resection for large colon polyps: a randomised trial","authors":"Heiko Pohl, Douglas K Rex, Jeremy Barber, Matthew T Moyer, B Joseph Elmunzer, Amit Rastogi, Stuart R Gordon, Eugene Zolotarevsky, John M Levenick, Harry R Aslanian, Mazen Elatrache, Daniel von Renteln, Michael B Wallace, Bhaumik Brahmbhatt, Rajesh N Keswani, Nikhil A Kumta, Douglas K Pleskow, Zachary L Smith, Mouhanna K Abu Ghanimeh, Stephen Simmer, Omid Sanaei, Todd A Mackenzie, Cyrus Piraka","doi":"10.1136/gutjnl-2025-335075","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335075","url":null,"abstract":"Background Complications of endoscopic mucosal resection (EMR) of large colorectal polyps remain a concern. Objective We aimed to compare safety and efficacy of cold EMR (without electrocautery) to hot EMR (with electrocautery) of large colorectal polyps. Design In this multicentre randomised trial, patients with any large (≥20 mm) non-pedunculated colon polyp were assigned to cold or hot EMR (primary intervention), and to submucosal injection with a viscous or non-viscous solution (secondary intervention) following a 2×2 design. The primary outcome was the rate of severe adverse events (SAEs). The secondary outcome was polyp recurrence. In this study, we report results of the primary intervention. Results 660 patients were randomised and analysed. An SAE was observed in 2.1% of patients in the cold EMR group and in 4.3% in the hot EMR group (p=0.10) (per protocol analysis 1.4 vs 5.0%, p=0.017) with fewer perforations following cold EMR (0%) compared with hot EMR (1.6%, p=0.028). Postprocedure bleeding did not differ (1.5% vs 2.2%, p=0.57). The effect of cold resection was independent of the type of submucosal injection solution, polyp size or antithrombotic medications. Recurrence was detected in 27.6% and 13.6% in the cold and hot EMR groups, respectively (p<0.001). Recurrence was not significantly different for 20–29 mm polyps (18.6% vs 13.4%, p=0.24) and for sessile serrated polyps (14.1% vs 8.5%, p=0.33). Conclusion Universal application of cold EMR did not significantly lower SAEs (unless cold EMR could be completed) and doubled the recurrence rate compared with hot EMR. Trial registration details ClinicalTrials.gov, number: [NCT03865537][1]. No data are available. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03865537&atom=%2Fgutjnl%2Fearly%2F2025%2F05%2F19%2Fgutjnl-2025-335075.atom","PeriodicalId":12825,"journal":{"name":"Gut","volume":"18 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-protein diets alleviate tumour growth and drug resistance by promoting AKT aggregation and turnover","authors":"Lang Bu, Yi Zhang, Yaqing Su, Xueji Wu, Bing Gao, Lei Wang, Wei Xie, Qiwei Jiang, Jianping Guo","doi":"10.1136/gutjnl-2024-334630","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334630","url":null,"abstract":"Background Despite the long-standing recommendations of high-protein diets for patients with cancer, the precise mechanisms of this dietary approach in benefiting tumour suppression and enhancing sensitivity to chemotherapy remain elusive. Objective To investigate the effect and underlying mechanism of high-protein diets in promoting cancer drug resistance. Characterisation of AKT regulation in this setting will provide new strategies to combat liver cancer. Design The role of high-protein diets in cancer drug resistance was analysed in cells and in syngeneic mouse models. In vivo and in vitro kinase and ubiquitination assays were employed to detect AKT phosphorylation and ubiquitination modifications. Clustered regularly interspaced short palindromic repeats (CRISPR)-based screen was used to identify the E3 ligase for AKT. Generation of Akt1T72E knock-in mice and Traf5 knockout mice was employed. Results High-protein diets repress tumour growth and sensitise tumour to chemotherapies. Specifically, S6K1 directly phosphorylates AKT, leading to acute inactivation and long-term instability of AKT protein. S6K1 promotes AKT aggregation and facilitates its interaction with TRAF5, resulting in AKT degradation in response to amino acid stimuli. Traf5 knockout mice exhibit high AKT protein levels, insulin resistance and counteracting protein diet-induced tumour repression. While a reversible phenomenon has been observed in the constitutive phosphor-mimetic Akt1T72E knock-in mice, which manifest retarded liver tumourigenesis in C-Myc transgenic mice. Conclusions Our results highlight a fine-tuned regulation of AKT by S6K1-mediated phosphorylation and TRAF5-dictated ubiquitination and degradation, offering a strategy for integrating chemotherapy with high-protein diets to enhance cancer treatment efficacy. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"6 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}