eGastroenterology最新文献

{"title":"eGastroenterology: a new chapter with exciting times ahead!","authors":"Emad M El-Omar, Guoyue Lyu","doi":"10.1136/egastro-2026-100427","DOIUrl":"10.1136/egastro-2026-100427","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100427"},"PeriodicalIF":10.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of metabolic dysfunction-associated steatotic liver disease in the Asia-Pacific region from 1990 to 2023.","authors":"Xiao-Dong Zhou, Qin-Fen Chen, Giovanni Targher, Christopher D Byrne, Luca Valenti, Mark D Muthiah, Seung Up Kim, Daniel Q Huang, Masato Yoneda, Wenhao Li, Yusuf Yilmaz, Herbert Tilg, Vincent Wai-Sun Wong, Ming-Hua Zheng","doi":"10.1136/egastro-2026-100369","DOIUrl":"10.1136/egastro-2026-100369","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing health problem in the Asia-Pacific region, contributing significantly to morbidity and healthcare burden. This study provides a comprehensive analysis of the burden of MASLD across countries and territories in the Asia-Pacific region from 1990 to 2023.</p><p><strong>Methods: </strong>We used the Global Burden of Disease 2023 data set to assess the burden of MASLD in the Asia-Pacific region, calculating age-standardised prevalence, incidence, death and disability-adjusted life year (DALY) rates. Temporal trends, age-specific and sex-specific patterns, and the relationship between MASLD burden and Socio-demographic Index (SDI) were also analysed, along with regional variations driven by ageing, population growth and epidemiological changes.</p><p><strong>Results: </strong>In 2023, MASLD prevalence varied across the Asia-Pacific region, with the highest rates in Oceania (15 360.55 per 100 000), Central Asia (15 201.10 per 100 000), South-East Asia (15 116.91 per 100 000) and East Asia (15 042.06 per 100 000), and lower rates in Australasia (9336.02 per 100 000) and high-income regions (8654.71 per 100 000). Over the past three decades, MASLD prevalence has increased across all regions, with the largest growth in Australasia (29%) and East Asia (27%). In addition, marked regional disparities were observed in age-standardised death and DALY rates, with Central Asia exhibiting the highest health loss across the region. Age-stratified analyses revealed that the highest incidence occurred in individuals aged 20-24 years in 2023. MASLD burden followed an inverse U-shaped pattern with SDI, increasing in regions with lower SDI and decreasing in those above 0.62. Population growth and lifestyle changes were the primary drivers of MASLD in East Asia, while ageing significantly contributed to the rising burden in South Asia.</p><p><strong>Conclusions: </strong>MASLD is increasingly prevalent across the Asia-Pacific region, driven by ageing, population growth and epidemiological changes, with significant regional variations in the disease burden.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100369"},"PeriodicalIF":10.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term and short-term outcomes of curative-intent resection for elderly and younger patients with gallbladder carcinoma: a multicentre propensity score-matched cohort study.","authors":"Yu Pan, Chun-Yue Ye, Peng Zhao, Hai-Su Dai, Yan Jiang, Yu-Cheng Huang, Cheng Chen, Yu-Le Luo, Jun-Jie Ding, Rui Ding, Ping Yue, Fan Huang, Chao Yu, Zhao-Ping Wu, Wei Chen, Jin-Xue Zhou, Wei Guo, Da-Long Yin, Wei Chen, Yi Zhu, Jie Bai, Yan-Qi Zhang, Dong Zhang, Ya-Yun Wang, Yan-Ling Yang, Zhi-Peng Liu, Rui Guo, Zhi-Yu Chen","doi":"10.1136/egastro-2025-100323","DOIUrl":"10.1136/egastro-2025-100323","url":null,"abstract":"<p><strong>Background: </strong>While curative-intent resection for gallbladder cancer (GBC) is being increasingly performed in elderly patients, perioperative morbidity and long-term oncological outcomes in this population remain unclear.</p><p><strong>Methods: </strong>Consecutive patients with GBC who underwent curative-intent resection (2016-2020) were identified from a multicentre database and stratified as elderly (>70 years) or younger (≤70 years). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimise selection bias. The outcomes compared included overall survival (OS), cancer-specific survival (CSS) and short-term outcomes. Logistic regression was used to identify risk factors for major morbidity and Cox regression was used for CSS, with the Fine-Gray competing risk model further applied to account for non-cancer-related death in the analysis of CSS.</p><p><strong>Results: </strong>Among the 575 patients enrolled, 432 were younger and 143 were elderly. After 1:1 PSM and IPTW, elderly patients had significantly higher 90-day major morbidity rates than younger patients (p=0.029 and p=0.010, respectively), but also demonstrated better CSS in both cohorts (p=0.038 and p<0.001, respectively). OS was significantly longer in elderly patients only after PSM (p<0.001), with no significant difference after IPTW (p=0.684). Multi-adjusted analysis confirmed that advanced age was an independent risk factor for major morbidities (original cohort: OR 1.71 (95% CI 1.12 to 2.59); PSM: OR 1.88 (95% CI 1.08 to 3.30); IPTW: OR 1.83 (95% CI 1.17 to 2.82)) but was associated with longer CSS (original cohort: HR 0.65 (95% CI 0.44 to 0.97); PSM: HR 0.29 (95% CI 0.18 to 0.45); IPTW: HR 0.62 (95% CI 0.42 to 0.90); Fine-Gray model: HR 0.34 (95% CI 0.30 to 0.39)).</p><p><strong>Conclusion: </strong>Despite a higher risk of major postoperative morbidity, advanced age itself might not be considered a contraindication for curative-intent resection. Selected elderly patients with GBC may achieve superior CSS compared to their younger counterparts.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100323"},"PeriodicalIF":10.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-dose taurine supplementation exacerbates alcohol-associated liver disease by inducing gut microbiota dysbiosis and bile acid dysregulation in mice.","authors":"Jingdan Pei, Lixian Chen, Rahul Pushparaj, Panpan Huang, Guihua Pan, Chunbao Sun, Xing Gao, Lihua Zhang, Md Manirujjaman, Chiung-Kuei Huang, Peng-Sheng Ting, Zhongbin Deng, Shaoyu Chen, Xiang Zhang, Vatsalya Vatsalya, Craig J McClain, Wenke Feng","doi":"10.1136/egastro-2025-100321","DOIUrl":"10.1136/egastro-2025-100321","url":null,"abstract":"<p><strong>Background: </strong>β-aminoethanesulfonic acid (taurine) is a conditionally essential amino acid that plays critical roles in bile acid (BA) conjugation, antioxidative defence and metabolic regulation. Previous studies showed that faecal taurine level was reduced in patients with alcohol-associated liver disease (ALD), suggesting that taurine supplementation may have beneficial effects. This study aimed to determine whether oral taurine supplementation prevents the development of ALD in mice and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>A total of 8-week-old male mice were subjected to a chronic-plus-binge ALD model. Taurine was administered orally via the diet for ten days before and during ethanol exposure. Faecal 16S ribosomal RNA metagenomic analysis, liver RNA sequencing and BA profiling were performed.</p><p><strong>Results: </strong>High-dose taurine supplementation (3 g/kg body weight/day) was associated with worsened ethanol-induced liver injury, as indicated by increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic steatosis, apoptosis and inflammation. At the molecular level, high-dose taurine treatment was associated with reduced <i>Cpt1a</i> expression, altered expression of genes involved in fatty acid β-oxidation and lipogenic gene <i>Fasn</i>, and decreased expression of <i>Baat</i>, accompanied by changes in taurine-conjugated BA profiles. These alterations were accompanied by changes in BA composition and intestinal FXR-associated gene expression. Taurine supplementation was also associated with shifts in gut microbial composition, including enrichment of hydrogen sulfide-producing bacteria, increased microbial H₂S production, impaired intestinal barrier-related parameters and increased bacterial translocation to the liver, paralleling enhanced hepatic inflammatory responses. In contrast, low-dose taurine supplementation (0.2 g/kg body weight/day) was associated with improved liver phenotypes, including reduced steatosis, lower serum ALT and AST levels, decreased <i>Fasn</i> expression and enhanced BA conjugation. Collectively, these results indicate a dose-dependent association between taurine supplementation and ALD-related outcomes.</p><p><strong>Conclusions: </strong>Our findings suggest that high-dose taurine supplementation is associated with unfavourable alterations in gut microbiota composition, intestinal barrier integrity, BA metabolism and hepatic taurine-related pathways in ALD, coinciding with exacerbated liver injury. In contrast, low-dose taurine supplementation was associated with improved hepatic outcomes. These results highlight the importance of dose considerations in taurine supplementation and support the concept that taurine may exert divergent effects on ALD depending on the administered dose.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100321"},"PeriodicalIF":10.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12970067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise and dietary interventions ameliorate MASLD via the hepatic PPARγ-miR-802-Psmd2 axis.","authors":"Yingying Liu, Jingjing Liu, Ping Song, Lin Sun, Zhiqiang Fang, Zhensheng Yue, Juanli Duan, Fei He, Lin Wang","doi":"10.1136/egastro-2025-100334","DOIUrl":"10.1136/egastro-2025-100334","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs critically regulate metabolic dysfunction-associated steatotic liver disease (MASLD) progression and intervention. Lifestyle modifications, particularly exercise and time-restricted feeding (TRF), emerge as effective non-pharmacological strategies.</p><p><strong>Methods: </strong>MiR-802 expression was quantified in plasma exosomes and hepatic tissues of MASLD mouse models using quantitative PCR and sequencing. In vivo and in vitro gain-of-function and loss-of-function experiments assessed its regulatory effects on hepatic lipotoxicity, complemented by bioinformatic predictions and luciferase-based validation of upstream transcription factors and downstream targets. Functional crosstalk between miR-802 and its regulatory network was examined under lipotoxic conditions. Therapeutic interventions, including exercise and TRF, were implemented in high-fat diet fed mice, with subsequent evaluation of miR-802 expression dynamics.</p><p><strong>Results: </strong>Here, we show elevated miR-802 levels in plasma exosomes and livers of MASLD mice, with its inhibition reducing hepatocyte lipotoxicity. Mechanistically, peroxisome proliferator-activated receptor gamma (PPARγ) promotes miR-802 transcription, whereas miR-802 suppresses the proteasome 26S subunit ubiquitin receptor, non-ATPase 2 (Psmd2). Genetic and pharmacological modulation of PPARγ downregulates miR-802 and ameliorates MASLD. Notably, both exercise and TRF reduce hepatic PPARγ and miR-802 expression and improve MASLD via the PPARγ-miR-802-Psmd2 axis, revealing lifestyle modification-mediated epigenetic regulation in MASLD pathophysiology.</p><p><strong>Conclusion: </strong>This study reveals the PPARγ-miR-802-Psmd2 axis as a central regulatory mechanism in MASLD pathogenesis and innovatively links lifestyle interventions (exercise and TRF) to therapeutic effects via this pathway.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100334"},"PeriodicalIF":10.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloidogenic phenotypical variation affects post-transplant outcome of hereditary transthyretin amyloidosis: a retrospective study.","authors":"Henryk E Wilczek, Marie Tranäng, Teresa Coelho, Bo-Göran Ericzon","doi":"10.1136/egastro-2025-100243","DOIUrl":"10.1136/egastro-2025-100243","url":null,"abstract":"<p><strong>Background: </strong>Liver transplantation (LTx) was once the standard of care for hereditary transthyretin amyloidosis (ATTRv), but transthyretin (TTR) stabilising and silencing therapies have supplanted it globally, partly because these therapies work in both hereditary and wild-type ATTR, avoids surgical risks and may improve outcomes across a wider patient population. LTx is now reserved for selected ATTRv cases where drug access or efficacy is limited. The Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR) was established in 1993 to analyse the outcome of LTx for ATTRv to support the international transplant society with selection criteria as the indication is rare at most centres.</p><p><strong>Methods: </strong>FAPWTR has, to date, secured data from over 30 years of follow-up. The registry holds data on 2267 patients who had LTx with various TTR variants from 82 centres in 21 countries. All patients studied presented with symptoms of polyneuropathy before LTx. The patient's pre-LTx phenotype was classified according to whether or not the heart and/or the kidney presented symptoms suggestive of amyloidotic involvement as reported by the submitting centre. The present study aims to evaluate the effect of these four different phenotypes on outcome as well as the mortality and morbidity in patients who had LTx with ATTRv.</p><p><strong>Results: </strong>Between 1990 and 2012, before pharmacotherapy became generally available as a treatment option, 1762 patients underwent isolated LTx. Overall, 25-year survival after LTx was 32.4%. Median survival time was 20.4 years. Cardiac and cardiorenal phenotypes were poor prognostic factors, while renal phenotype was not. The cardiac phenotype had statistically significantly worse survival compared with all other phenotypes. Median survival for the cardiac, cardiorenal and polyneuropathy-only phenotype were 15.2, 20.8 and 22.7 years, respectively. Age at transplant, disease duration and modified body mass index had a statistically significant impact on survival. Deterioration of autonomic neuropathy occurred earlier than deterioration of peripheral neuropathy and deterioration of extraneurological symptoms and may be an important marker for additional pharmacological treatment in LTx recipients with disease progression.</p><p><strong>Conclusion: </strong>The FAPWTR provides a useful tool to study late effects of LTx as a disease-modifying therapy for ATTRv and may be important for comparison and evaluation of the long-term effects of the various novel pharmacotherapies used today.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100243"},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12878299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced fibre-fermenting capacity of gut microbes in multiple sclerosis may result in prebiotic dietary fibre β-fructan promoting inflammation and CNS damage.","authors":"Stephanie L Tollenaar, Reihane Khorasaniha, Juan Jovel, Ismaila Ba, Athalia Voisin, Richard Miller, Hana Olof, Ramsha Mahmood, Ruth Ann Marrie, Erin Strachan, Luisa P Soares, Christopher Cheng, Jonathan Janveaux, Deenaz Zaidi, Charles N Bernstein, Christine Bonner, Amit Bar-Or, Emmanuelle Waubant, E Ann Yeh, Morag Graham, Douglas L Arnold, Julia O'Mahony, Brenda L Banwell, Feng Zhu, Ali I Mirza, Soheila Karimi-Abdolrezaee, Sue Tsai, Helen Tremlett, Kevin McGregor, Benjamin P Willing, Heather Armstrong","doi":"10.1136/egastro-2025-100296","DOIUrl":"10.1136/egastro-2025-100296","url":null,"abstract":"<p><strong>Background: </strong>Some people with multiple sclerosis display changes in their gut microbiota with separate evidence suggesting that symptoms may worsen following a high-fibre diet. We hypothesised that in people with multiple sclerosis whose gut microbiota are less able to efficiently ferment dietary fibres, unfermented β-fructans induce inflammation.</p><p><strong>Methods: </strong>Diet data (n=48 individuals with multiple sclerosis, n=78 unaffected controls) and stool microbiome data (n=31 individuals with multiple sclerosis, n=61 unaffected controls) were previously collected from participants. Daily fibre subtype intakes were calculated and compared with faecal shotgun metagenomic sequencing in paediatric onset multiple sclerosis and unaffected persons. Response to unfermented β-fructans was examined in a germ-free experimental autoimmune encephalomyelitis (EAE) mouse model (unable to ferment fibres). Mice were fed β-fructans or control fibre diet beginning at symptom onset (day 14). EAE scores and weights were recorded daily. Intestinal and central nervous system tissues were collected at two endpoints to examine inflammatory responses and demyelinating lesions.</p><p><strong>Results: </strong>Individuals with paediatric onset multiple sclerosis consumed less β-fructans (2.4 g/day±0.3 SD; p<0.05) than unaffected participants (3.6 g/day±0.4), which coincided with differences in the gut microbiota including lower fibre fermenting enzymes. Mice exposed to unfermented β-fructans sustained worsened EAE symptoms (day 20-28; p<0.05), immune activation in the gut and immune activation plus demyelinating lesions in the spinal cord compared with mice on control diet.</p><p><strong>Conclusions: </strong>The gut microbiota of individuals with paediatric-onset multiple sclerosis showed reduced fibre fermenting properties, and our animal findings suggest that unfermented β-fructans can worsen demyelination and promote gut-brain axis immune activation. Lower β-fructan consumption was observed among participants with paediatric-onset multiple sclerosis. Future longitudinal studies are warranted to confirm the findings uncovered in this manuscript.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100296"},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12829359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Regulatory T cells in liver metastases: emerging and divergent roles in tumour progression.","authors":"","doi":"10.1136/egastro-2025-100257corr1","DOIUrl":"https://doi.org/10.1136/egastro-2025-100257corr1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1136/egastro-2025-100257.].</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100257corr1"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12815015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Massive hepatic necrosis-associated acute liver failure.","authors":"Tao Lin, Chenhao Tong, Roman Liebe, Honglei Weng","doi":"10.1136/egastro-2025-100217","DOIUrl":"10.1136/egastro-2025-100217","url":null,"abstract":"<p><p>Massive hepatic necrosis (MHN), characterised by extensive loss of hepatocytes, represents the most severe pathological lesion in acute liver failure (ALF). MHN-associated ALF primarily occurs in patients with acute viral hepatitis A, B or E infections. Additionally, MHN-associated ALF can develop in patients with autoimmune hepatitis or in those taking idiosyncratic drugs. MHN-associated ALF is associated with significantly higher mortality than that caused by other aetiologies. In contrast to other forms of ALF, liver regeneration following MHN depends on liver progenitor cells (LPCs)-the smallest cholangiocytes localising in the canal of Hering and terminal biliary branches. These cells play key roles in determining the clinical outcome of patients with MHN-associated ALF. This paper reviews the pathophysiology of MHN-associated ALF and recent advances in LPC biology.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 1","pages":"e100217"},"PeriodicalIF":10.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12815235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of machine learning in the discovery of antimicrobial peptides: exploring their potential for ulcerative colitis therapy.","authors":"Hui Miao, Ziwei Wang, Shihu Chen, Jiaqi Wang, Hongyue Ma, Yifan Liu, Hui Yang, Ziyi Guo, Jiamei Wang, Pengfei Cui","doi":"10.1136/egastro-2025-100253","DOIUrl":"10.1136/egastro-2025-100253","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease with complex aetiology and limited treatment options. Antimicrobial peptides (AMPs), as endogenous immune effectors, have recently emerged as promising therapeutic agents in UC. However, systematic identification and functional evaluation of AMPs remain underexplored. We aimed to discover novel AMPs with potential therapeutic efficacy in UC by leveraging machine learning-based prediction and validating their impact in an experimental colitis model.</p><p><strong>Methods: </strong>We established a machine learning-driven pipeline to predict candidate AMPs based on their structural and functional features. Top-ranked peptides were synthesised and subjected to in vitro antibacterial assays and proteolytic stability tests. Their therapeutic potential was evaluated using a dextran sulfate sodium (DSS)-induced colitis mouse model, assessing clinical indicators, histopathology, inflammatory markers and gut microbiota alterations. Metagenomic and metabolomic analyses provided insights into microbial community dynamics and metabolic pathways. To probe the role of gut microbes in AMP-mediated gut homeostasis, we conducted <i>Akkermansia (A.) muciniphila</i> replenishment experiments.</p><p><strong>Results: </strong>Several AMPs identified by machine learning exhibited potent antimicrobial activity and resistance to proteolytic degradation. In vivo, AMP administration ameliorated DSS-induced colitis symptoms, including body weight loss, Disease Activity Index and histological damage. Treatment also modulated the gut microbiome, increasing the abundance of <i>A. muciniphila</i> and restoring microbial balance. Functional metagenomic profiling revealed enrichment of genes involved in mucosal barrier protection and immunoregulation. These findings were supported by improved inflammatory cytokine profiles and enhanced epithelial integrity.</p><p><strong>Conclusions: </strong>Our findings demonstrate that machine learning-guided discovery of AMPs is a viable approach to identify promising therapeutic agents for UC. By integrating multi-omics analyses, we reveal potential microbiota-mediated mechanisms underlying AMP efficacy. These insights provide a strong foundation for advancing AMP-based strategies in UC management.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 4","pages":"e100253"},"PeriodicalIF":0.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}