Gut最新文献

{"title":"AlphaMissense versus laboratory-based pathogenicity prediction of 13 novel missense CPA1 variants from pancreatitis cases","authors":"Máté Sándor, Isabelle Scheers, Atsushi Masamune, Heiko Witt, Jessica LaRusch, Jian-Min Chen, Balázs Csaba Németh, Andrea Geisz, Aliye Uc, Miklós Sahin-Tóth","doi":"10.1136/gutjnl-2024-333697","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333697","url":null,"abstract":"We have read with great interest the study by Wang et al 1 in which the authors evaluated the utility of the AlphaMissense prediction programme2 (https://alphamissense.hegelab.org) in the classification of missense CPA1 variants with respect to pathogenicity in chronic pancreatitis. While the AI-driven prediction performed relatively well, the authors highlighted potential shortcomings that can limit its value in clinical practice. Defining the pathogenic potential of CPA1 variants detected in pancreatitis cases can be challenging because the mechanistic basis of disease risk is unrelated to loss of CPA1 function and seems to be determined by mutation-induced misfolding and the ensuing endoplasmic reticulum (ER) stress.3–5 Recently, we used transiently transfected HEK 293T cells to measure the secretion efficiency and induction of BiP mRNA expression, a marker of ER stress, for 50 missense CPA1 variants from pancreatitis cases and healthy controls.6 We found that the best predictor of pathogenicity was loss of secretion (<10% of wild type) irrespective of BiP levels. This data set can serve as a reference for the assignment of clinical significance of novel CPA1 variants. In the present study, we set out to examine what fraction of novel CPA1 variants detected in real-world genetic testing can be classified as pathogenic and whether AlphaMissense can replace …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166206","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":"Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy","authors":"Qiming Zhou, Linhan Lei, Junhong Cheng, Junyou Chen, Yuyang Du, Xuehua Zhang, Qing Li, Chuangen Li, Haijun Deng, Chi Chun Wong, Baoxiong Zhuang, Guoxin Li, Xiaowu Bai","doi":"10.1136/gutjnl-2024-332193","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332193","url":null,"abstract":"Background Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. Objective We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis. Design Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results. Results Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11+ epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer. Conclusion Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160545","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":"Sphincterotomy for biliary sphincter of Oddi disorder and idiopathic acute recurrent pancreatitis: the RESPOnD longitudinal cohort.","authors":"Gregory A Coté, Badih Joseph Elmunzer, Haley Nitchie, Richard S Kwon, Field Willingham, Sachin Wani, Vladimir Kushnir, Amitabh Chak, Vikesh Singh, Georgios I Papachristou, Adam Slivka, Martin Freeman, Srinivas Gaddam, Priya Jamidar, Paul Tarnasky, Shyam Varadarajulu, Lydia D Foster, Peter Cotton","doi":"10.1136/gutjnl-2024-332686","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332686","url":null,"abstract":"<p><strong>Objective: </strong>Sphincter of Oddi disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurisation at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD.</p><p><strong>Design: </strong>Prospective cohort conducted at 14 US centres with 12 months follow-up. Patients undergoing first-time endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy for suspected SOD were eligible: pancreatobiliary-type pain with or without iAP. The primary outcome was defined as the composite of improvement by Patient Global Impression of Change (PGIC), no new or increased opioids and no repeat intervention. Missing data were addressed by hierarchal, multiple imputation scheme.</p><p><strong>Results: </strong>Of 316 screened, 213 were enrolled with 190 (89.2%) of these having a dilated bile duct, abnormal labs, iAP or some combination. By imputation, an average of 122/213 (57.4% (95% CI 50.4% to 64.4%)) improved; response rate was similar for those with complete follow-up (99/161, 61.5% (54.0% to 69.0%)); of these, 118 (73.3%) improved by PGIC alone. Duct size, elevated labs and patient characteristics were not associated with response. AP occurred in 37/213 (17.4%) at a median of 6 months post ERCP and was more likely in those with a history of AP (30.9% vs 2.9%, p<0.0001).</p><p><strong>Conclusion: </strong>Nearly 60% of patients undergoing ERCP for suspected SOD improve, although the contribution of a placebo response is unknown. Contrary to prevailing belief, duct size and labs are poor response predictors. AP recurrence was common and like observations from prior non-intervention cohorts, suggesting no benefit of sphincterotomy in mitigating future AP episodes.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":23.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145555","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":"Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease","authors":"Sungho Bea, Hwa Yeon Ko, Jae Hyun Bae, Young Min Cho, Yoosoo Chang, Seungho Ryu, Christopher D Byrne, Ju-Young Shin","doi":"10.1136/gutjnl-2024-332687","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332687","url":null,"abstract":"Objective To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Design This population-based cohort study was conducted using a nationwide healthcare claims database (2014–2022) of Korea. We included individuals with MASLD (aged ≥40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs. Results After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80–0.94); female: HR 0.62 (95% CI 0.55–0.69)). Conclusions In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA. No data are available. The corresponding author will provide data from this study upon request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144320","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":"Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021","authors":"Pojsakorn Danpanichkul, Kanokphong Suparan, Primrose Tothanarungroj, Disatorn Dejvajara, Krittameth Rakwong, Yanfang Pang, Romelia Barba, Jerapas Thongpiya, Michael B Fallon, Denise Harnois, Rashid N Lui, Michael B Wallace, Ju Dong Yang, Lewis R Roberts, Karn Wijarnpreecha","doi":"10.1136/gutjnl-2024-333227","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333227","url":null,"abstract":"Background Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. Objective We aimed to assess the global, regional and national burden of gastrointestinal cancers. Designs Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI). Results In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer. Conclusions Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers—most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases. Data are available in a public, open access repository. Data from the Global Burden of Disease (GBD) study in 2021 can be accessed using the Global Health Data Exchange (GHDx) query tool (<http://ghdx.healthdata.org/gbd-results-tool>) which the Institute for Health Metrics and Evaluation maintains. The GBD data do not require licensing for non-commercial use.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144318","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":"Cholesterol’s new tricks propel MASH-HCC: impact in immunotherapy","authors":"Carmen Garcia-Ruiz, Sandra Torres, Jose C Fernandez-Checa","doi":"10.1136/gutjnl-2024-332766","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332766","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the end-stage of chronic liver diseases, including metabolic-associated steatohepatitis (MASH), an advanced form of metabolic dysfunction-associated steatotic liver disease. The incidence of MASH-driven HCC is expected to continue rising throughout the world due to its association with the obesity and type 2 diabetes epidemic.1 HCC has a poor prognosis with frequent recurrence and intrahepatic metastasis and effective treatment options, such as local ablative therapies, resection or transplantation are mainly limited to early disease stages.1 Unfortunately, the therapeutic armamentarium for HCC is limited, ineffective and subject to secondary or acquired chemoresistance indicating the urgent need to understand the molecular mechanisms leading to MASH-HCC that will allow the identification of new therapeutic targets for the treatment of MASH-HCC development. Although targeting programmed death-ligand 1/programmed cell death protein-1 (PD-1) in the tumour immune microenvironment (TIME) with immune checkpoint inhibitors has shown promising results in different cancer types, the impact of this approach in HCC is somewhat less effective, particularly in MASH-driven HCC tumours which harbour a unique TIME with an accumulation of an exhausted T-cell subsets (CD8+ PD-1+) contributing to the refractory response to anti-PD-1 therapy.2 Since the description that the type rather than the amount of fat drives the transition from steatosis to MASH,3 cholesterol has emerged as a crucial player in MASH pathogenesis and MASH-driven HCC development in part through the generation of bile acids (BAs) via the alternative pathway in which mitochondrial cholesterol is metabolised to the oxysterol 27-hydroxycholesterol to fuel BAs synthesis.4 Previous studies demonstrated that de novo cholesterol synthesis in the mevalonate pathway propels MASH progression5 with a crucial role of squalene epoxidase (SLQE) in MASH-HCC development whose expression is associated with poor outcome in patients with MASH-HCC. …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144270","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":"Incorporating all the evidence: the role of EGJ-CI in GERD diagnosis","authors":"Humayra Dervin, Rami Sweis","doi":"10.1136/gutjnl-2023-331362","DOIUrl":"https://doi.org/10.1136/gutjnl-2023-331362","url":null,"abstract":"We have read with interest the recent paper by Gyawali et al .1 The authors deserve commendation for their efforts in developing an update to the Lyon Consensus 2.0, a substantial undertaking involving expert contributors worldwide to establish criteria for diagnosing gastro-esophageal reflux disease (GERD). They have introduced new normal values for existing parameters, such as mean nocturnal baseline impedance (MNBI), ambulatory pH monitoring whilst on proton pump inhibitors (PPIs) and prolonged wireless pH monitoring. Notably, the EGJ contractile integral (EGJ-CI) serves as a measure of …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138222","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":"Where are we with gastric cancer screening in Europe in 2024?","authors":"Mārcis Leja","doi":"10.1136/gutjnl-2024-332705","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332705","url":null,"abstract":"The absolute number of annual cases of gastric cancer in Europe is rising. The Council of the European Union has recommended implementation of gastric cancer screening for countries or regions with a high gastric cancer incidence and death rates. However, as of 2024 no organised gastric cancer screening programme has been launched in Europe. There are several ways to decrease gastric cancer burden, but the screen and treat strategy for Helicobacter pylori (H. pylori ) seems to be the most appropriate for Europe. It has to be noted that increased use of antibiotics would be associated with this strategy. Only organised population-based cancer screening is recommended in the European Union, therefore gastric cancer screening also is expected to fulfil the criteria of an organised screening programme. In this respect, several aspects of screening organisation need to be considered before full implementation of gastric cancer prevention in Europe; the age range of the target group, test types, H. pylori eradication regimens and surveillance strategies are among them. Currently, ongoing projects (GISTAR, EUROHELICAN, TOGAS and EUCanScreen) are expected to provide the missing evidence. Feedback from the decision-makers and the potential target groups, including vulnerable populations, will be important to planning the programme. This paper provides an overview of the recent decisions of the European authorities, the progress towards gastric cancer implementation in Europe and expected challenges. Finally, a potential algorithm for gastric cancer screening in Europe is proposed.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138307","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":"MED12 loss activates endogenous retroelements to sensitise immunotherapy in pancreatic cancer","authors":"Yingying Tang, Shijie Tang, Wenjuan Yang, Zhengyan Zhang, Teng Wang, Yuyun Wu, Junyi Xu, Christian Pilarsky, Massimiliano Mazzone, Lei-Wei Wang, Yongwei Sun, Ruijun Tian, Yujie Tang, Yu Wang, Chaochen Wang, Jing Xue","doi":"10.1136/gutjnl-2024-332350","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332350","url":null,"abstract":"Objective Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by its lethality and limited treatment options, including the utilisation of checkpoint blockade (ICB) immunotherapy. Epigenetic dysregulation is a defining feature of tumourigenesis that is implicated in immune surveillance, but remains elusive in PDAC. Design To identify the factors that modulate immune surveillance, we employed in vivo epigenetic-focused CRISPR-Cas9 screen in mouse PDAC tumour models engrafted in either immunocompetent or immunodeficient mice. Results Here, we identified MED12 as a top hit, emerging as a potent negative modulator of immune tumour microenviroment (TME) in PDAC. Loss of Med12 significantly promoted infiltration and cytotoxicity of immune cells including CD8+ T cells, natural killer (NK) and NK1.1+ T cells in tumours, thereby heightening the sensitivity of ICB treatment in a mouse model of PDAC. Mechanistically, MED12 stabilised heterochromatin protein HP1A to repress H3K9me3-marked endogenous retroelements. The derepression of retrotransposons induced by MED12 loss triggered cytosolic nucleic acid sensing and subsequent activation of type I interferon pathways, ultimately leading to robust inflamed TME . Moreover, we uncovered a negative correlation between MED12 expression and immune resposne pathways, retrotransposon levels as well as the prognosis of patients with PDAC undergoing ICB therapy. Conclusion In summary, our findings underscore the pivotal role of MED12 in remodelling immnue TME through the epigenetic silencing of retrotransposons, offering a potential therapeutic target for enhancing tumour immunogenicity and overcoming immunotherapy resistance in PDAC. Data are available on reasonable request. All genomic sequencing data involved in this study have been deposited in the Gene Expression Omnibus database with the accession code GSE242098.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100846","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":"Breast milk components modulate gut microbiota to increase susceptibility to atopic dermatitis in early life","authors":"Ruiqi Zhang, Jinfeng Wang","doi":"10.1136/gutjnl-2024-333235","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333235","url":null,"abstract":"The colonisation and assembly of the neonatal microbiota is essential for the development and maturation of the immune system, and the early life from birth to 2 years of age is regarded as a crucial window period. Abnormal microbial colonisation and reduced gut microbiota diversity during this period are linked to the subsequent development of immune-mediated diseases. Dysbiosis of intestinal microbiota in early life can promote dysfunction of the CD4+ T-cell population,1 impacting the development of the child’s immune system and increasing the risk of atopic diseases. Atopic diseases are excessive IgE-mediated immune responses that commonly affect the nose, eyes, skin and lungs. Of these, atopic dermatitis (AD), a chronic and recurring inflammatory skin disease, affects at least 10%–20% of children, often starting in infancy and continuing into adulthood.2 The factors influencing AD are complex. Researchers have conducted meta-analyses of the various factors correlating to the onset of AD in terms of external exposures, individual factors, mechanisms and other diseases, and proposed that factors related to microbiota and infant feeding may play a role in influencing the development of AD, including exclusive breast feeding or formula feeding, duration of breast feeding and timing of food introduction (figure 1 and online supplemental table S1). Some studies have reported that infants exclusively breastfed for more than 3–4 months are less likely to develop AD, especially in the first 4 months of life.3 However, the relationship between breast feeding and AD is controversial. In the Copenhagen longitudinal birth cohort, there was no significant association between the duration of exclusive breast feeding and the development of sensitisation in the first 6 years of life.4 A similar result was also found in Riyadh, where no associations were demonstrable between full or ever breast feeding …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100878","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}