Digestion[JOURNAL]
Sun
200 papers
Colonization of <italic>Streptococcus pyogenes</italic> Is Associated with Functional Dyspepsia and Exacerbates Functional Dyspepsia in Mice by Inhibiting the RhoA/ROCK1 Pathway through the Skin-Gut Axis.
Lin Y, Wang C, Fang M … +5 more , You H, Li J, Huang S, Xu C, Wang L
Digestion · 2025 Jun · PMID 40545790 · Publisher ↗
INTRODUCTION: We investigated the importance of skin microbiota in functional dyspepsia (FD) based on the skin-gut axis theory and revealed potential mechanisms. This study also validates recent popular FD treatments. ME...
INTRODUCTION: We investigated the importance of skin microbiota in functional dyspepsia (FD) based on the skin-gut axis theory and revealed potential mechanisms. This study also validates recent popular FD treatments. METHODS: We used mendelian randomization (MR) to analyze 418 gut bacteria and 145 skin bacteria, identifying key symbionts in FD development. Bibliometric keyword analysis was conducted on current FD therapies. Finally, we used a mouse model of FD to assess body weight, food intake, gastric residue rate, small intestine transit rate, and fecal water content after interventions with skin-gut symbionts and treatment methods. Hematoxylin-eosin staining observed gastric antrum tissue morphology. RhoA and ROCK1 protein and mRNA levels in gastric antrum tissue were detected by western blot and real-time PCR. Fluorescence immunoassay observed ROCK1 and vesicular acetylcholine transporter (VAChT) protein expression. RESULTS: Streptococcus has a causal relationship with FD. Bibliometric analysis highlighted electroacupuncture as a research hotspot. Skin Streptococcus colonization reduced food intake, body weight, small intestine transit rate, and increased gastric residue rate in FD mice, decreasing RhoA, ROCK1, and VAChT protein and mRNA levels. Antibiotics reversed these effects. Electroacupuncture improved weight, appetite, gastrointestinal motility, and RhoA, ROCK1, and VAChT protein, and mRNA levels in FD mice. CONCLUSION: The study confirmed the pathogenic role of skin Streptococcus in FD and the therapeutic value of electroacupuncture at Tianshu acupoint, potentially via RhoA/ROCK1 signaling pathway regulation.
Clinicopathological and Endoscopic Features of Non-Ampullary Duodenal Epithelial Tumors with Gastrointestinal Mixed Phenotype.
Yamamoto M, Akazawa Y, Suzuki N … +17 more , Ueyama H, Nakamura S, Uemura Y, Iwano T, Uchida R, Utsunomiya H, Abe D, Oki S, Ikeda A, Takeda T, Ueda K, Hojo M, Hashiguchi T, Hashimoto T, Mine S, Yao T, Nagahara A
Digestion · 2026 · PMID 40544828 · Full text
UNLABELLED: <p>Introduction: Non-ampullary duodenal epithelial tumors with a gastrointestinal mixed phenotype (mixed-type NADETs) have not been thoroughly analyzed. We aimed to elucidate the clinicopathological and endos...
UNLABELLED: <p>Introduction: Non-ampullary duodenal epithelial tumors with a gastrointestinal mixed phenotype (mixed-type NADETs) have not been thoroughly analyzed. We aimed to elucidate the clinicopathological and endoscopic characteristics of mixed-type NADETs. METHODS: A total of 229 NADETs from 218 patients collected from February 2010 to December 2023 were analyzed. Based on immunohistochemistry for MUC5AC, MUC6, MUC2, and CD10, the NADETs were classified into gastric phenotype (GP), gastric predominant mixed phenotype (GPP), intestinal predominant mixed phenotype (IPP), and intestinal phenotype (IP). RESULTS: Among the 229 NADETs, there were 20, 22, 69, and 118 lesions classified as GP, GPP, IPP, and IP, respectively. Tumor location (first/second/third) was GP = 13/7/0, GPP = 12/8/2, IPP = 13/52/4, and IP = 16/94/8 (p < 0.01). Mean tumor sizes of GP, GPP, IPP, and IP were 14.7/18.5/10.9/10.3 mm (p < 0.01), respectively. The ratio of category 4/5 by Vienna classification was 50.0, 68.2, 13.0, and 2.5% (p < 0.01), respectively. In the comparisons between GP vs. GPP and IP vs. IPP, white opaque substance was significantly less frequently observed in GP than in GPP (p < 0.05), the ratio of category 4/5 was significantly higher in IPP than in IP (p < 0.01), but no significant differences were observed in tumor location, coloration, macroscopic type, and endoscopic findings including magnifying endoscopy with narrow-band imaging. CONCLUSION: Mixed-type NADETs (GPP and IPP) exhibited similar endoscopic and clinicopathological characteristics to their predominant phenotypes, and may have a higher malignant potential than the pure phenotypes. </p>.
Timing and Predictors for Vonoprazan Dose Escalation in Refractory Gastroesophageal Reflux Disease: A Long-Term Observational Study.
Shinozaki S, Sakamoto H, Osawa H … +3 more , Yano T, Lazaridis N, Yamamoto H
Digestion · 2026 · PMID 40527300 · Publisher ↗
INTRODUCTION: Vonoprazan (VPZ) therapy has become one of the standard treatments for gastroesophageal reflux disease (GERD). When GERD symptoms persist despite the maintenance dose therapy (10 mg daily), dose escalation...
INTRODUCTION: Vonoprazan (VPZ) therapy has become one of the standard treatments for gastroesophageal reflux disease (GERD). When GERD symptoms persist despite the maintenance dose therapy (10 mg daily), dose escalation to 20 mg daily is generally recommended. This study aims to clarify the proper timing and predictors for dose escalation of VPZ therapy in patients with refractory GERD treated with the maintenance dose. METHODS: This retrospective observational study included 257 patients with symptomatic GERD. Data from medical records, including endoscopic findings and Izumo scale scores, were analyzed. RESULTS: The mean follow-up period was 3.3 years. Throughout the follow-up period, VPZ dose escalation (from 10 to 20 mg daily) was required in 56 of 257 patients (22%). Kaplan-Meier analysis showed cumulative dose-escalation-free rates at 6 months, 1 year, and 2 years were 87%, 81%, and 78%, respectively. Predictive factors for VPZ dose escalation were analyzed using a Cox proportional-hazards regression model. Multivariate analysis revealed that pre-existing epigastric pain was a significant positive predictor for dose escalation, whereas pre-existing constipation was identified as a significant negative predictor. Kaplan-Meier analysis indicated that the 1-year dose-escalation-free rates were 69% in patients with epigastric pain compared to 88% in those without (p = 0.001). GERD symptom scores showed a significant improvement 1 month after dose escalation. CONCLUSION: The incidence of refractory GERD requiring VPZ dose escalation is relatively low. Epigastric pain prior to VPZ initiation independently predicts the need for dose escalation. VPZ dose escalation effectively improves GERD symptoms.
Texture and Colour Enhancement Imaging versus White Light Endoscopy for Detection of Dysplasia within Barrett's Oesophagus: A Pilot Study.
Young E, Philpott H, Singh R
Digestion · 2026 · PMID 40523357 · Full text
UNLABELLED: <p>Introduction: Oesophageal cancer is a leading global health issue, with increasing prevalence of oesophageal adenocarcinoma and its precursor lesion, Barrett's oesophagus (BE). Despite the opportunity to t...
UNLABELLED: <p>Introduction: Oesophageal cancer is a leading global health issue, with increasing prevalence of oesophageal adenocarcinoma and its precursor lesion, Barrett's oesophagus (BE). Despite the opportunity to treat dysplasia prior to adenocarcinoma development, rates of missed advanced dysplasia at BE surveillance remain high. This pilot study aimed to assess whether Texture and Colour Enhancement Imaging (TXI), a new advanced mucosal imaging modality, improves dysplasia detection during BE surveillance compared to white light endoscopy (WLE). METHODS: Patients undergoing endoscopy for BE assessment or surveillance at a single centre were included for analysis. Patients were randomized in a 1:1 ratio to examination with WLE then TXI or vice versa, followed by narrow-band imaging (NBI). Targeted biopsies were taken from any suspicious areas and 4-quadrant surveillance biopsies were taken at 1 cm intervals in the entire BE segment. RESULTS: A total of 50 patients were included in the study, with 27 suspicious lesions seen in 22 patients. A total 93.3% (n = 14/15) of high-grade dysplasia or early adenocarcinoma was detected as endoscopically visible lesions on TXI and NBI. However, 4 such lesions were not detected on WLE. On per-patient analysis, the sensitivity and NPV of TXI in combination with magnified NBI were both 100% with specificity of 84.6%, surpassing all PIVI thresholds for dysplasia diagnosis in BE. CONCLUSION: This pilot study demonstrates the feasibility of TXI as a potential addition to the armamentarium of advanced mucosal imaging available to proceduralists surveilling BE. Further large multi-centre studies would be required to make statistical comparisons with existing imaging modalities. </p>.
Role of Endoscopy in Achalasia.
Kawami N, Hoshikawa Y, Momma E … +2 more , Hoshino S, Iwakiri K
Digestion · 2026 · PMID 40523354 · Publisher ↗
BACKGROUND: Esophagogastroduodenoscopy is often performed as an initial examination in patients with symptoms such as dysphagia or chest pain, which may suggest esophageal motility disorders. However, its current role is...
BACKGROUND: Esophagogastroduodenoscopy is often performed as an initial examination in patients with symptoms such as dysphagia or chest pain, which may suggest esophageal motility disorders. However, its current role is largely limited to ruling out organic diseases. SUMMARY: High-resolution manometry (the gold standard for diagnosing primary esophageal motility disorders such as achalasia) along with esophagography is extremely useful for diagnosis. In recent years, however, several new endoscopic findings - esophageal rosette, gingko leaf sign, champagne glass sign, corona appearance, and pinstripe pattern - have been reported, making it increasingly possible to strongly suspect achalasia through endoscopy. Additionally, the presence of multiple annular contractions, spiral (corkscrew) contractions, or narrowing (poor distensibility) in the esophageal body during endoscopy may suggest abnormal motility of the esophageal body. KEY MESSAGES: When performing endoscopic examinations in patients with symptoms such as dysphagia or chest pain, it is important to consider the possibility of esophageal motility disorders. Careful endoscopic observation may allow for the suspicion of such disorders during the examination itself.
Esophageal Hypervigilance and Visceral Anxiety Are Involved in Esophageal Symptom Perception in Patients with Systemic Sclerosis.
Hoshikawa Y, Suzuki M, Momma E … +5 more , Hoshino S, Kawami N, Kuwana M, Iwakiri K, Atsukawa M
Digestion · 2026 · PMID 40517755 · Publisher ↗
INTRODUCTION: Systemic sclerosis (SSc) causes esophageal motility disorders. However, esophageal symptom severity often does not correlate with the physiological findings of high-resolution manometry (HRM) in patients wi...
INTRODUCTION: Systemic sclerosis (SSc) causes esophageal motility disorders. However, esophageal symptom severity often does not correlate with the physiological findings of high-resolution manometry (HRM) in patients with SSc. Esophageal hypervigilance and visceral anxiety play a relevant role in symptom perception in patients with gastroesophageal reflux disease and esophageal motility disorders. Therefore, the present study examined the effects of anxiety and hypervigilance, along with HRM findings, on esophageal symptom severity in patients with SSc. METHODS: We reviewed the clinical data of consecutive patients with SSc who underwent HRM and were assessed using the esophageal hypervigilance and anxiety scale (EHAS) at our hospital between January 2022 and February 2025. Predictors for the Eckardt symptom score (ESS) and gastroesophageal reflux disease questionnaire (GerdQ) were investigated. RESULTS: This study included 51 patients with SSc. Significant differences were observed in EHAS scores between patients with ESS >3 and those with ESS ≤3 (34.0 [24.0-42.0] vs. 13.0 [1.0-24.0], p = 0.003), but not in HRM findings. The EHAS score accounted for 38.2% of the variance in the ESS score. Significant differences were also observed in the EHAS score between patients with GerdQ ≥8 and those with GerdQ <8 (26.0 [14.3-32.5] vs. 13.0 [0-22.0], p = 0.011). The combined factors of the EHAS score and absent contractility accounted for 17.3% of the variance in the GerdQ score. CONCLUSION: Esophageal hypervigilance and anxiety may be involved in esophageal symptom severity, particularly dysphagia severity, in patients with SSc. Further studies involving interventions targeting these conditions, such as cognitive behavioral therapy, are warranted.
Cost-Effective Endoscopic Screening Strategies for Asymptomatic Gastric Cancer.
Ishibashi F, Okusa K
Digestion · 2025 · PMID 40472817 · Publisher ↗
BACKGROUND: In Japan, biennial esophagogastroduodenoscopy (EGD) screening for gastric cancer (GC) has been implemented for adults aged ≥50 years as part of a population-based screening program. This approach has facilita...
BACKGROUND: In Japan, biennial esophagogastroduodenoscopy (EGD) screening for gastric cancer (GC) has been implemented for adults aged ≥50 years as part of a population-based screening program. This approach has facilitated early GC detection and demonstrated individual-level benefits. However, due to a generational decline in Helicobacter pylori infection, a reduction in the long-term effectiveness of this strategy is anticipated. Given the allocation of national resources, a cost-effectiveness evaluation is essential. SUMMARY: As GC prevalence declines in the target population, the cost-effectiveness of existing screening practices may diminish. Mathematical simulation models are commonly employed to assess the comparative effectiveness and cost-effectiveness of various cancer screening strategies. Microsimulation models, which track individual-level outcomes, are utilized to evaluate person-level effects. By contrast, macrosimulation models - such as Markov and decision tree models - are used to assess population-level outcomes. KEY MESSAGES: Nine studies have compared different EGD screening strategies. These studies support the effectiveness of biennial screening in high-risk countries. In low- to intermediate-risk countries - and among lower risk populations within high-risk countries - extending the screening interval to ≥3 years appears reasonable. Additionally, strategies incorporating risk stratification using alternative modalities, such as serological tests, are more cost-effective. Continued discussion is necessary to optimize the EGD screening approach.
Regulation of Colonic Motility by Cystathionine γ-Lyase Neuron Remodeling.
Liang S, Fang H, Jia G … +1 more , Liu Y
Digestion · 2025 · PMID 40451150 · Publisher ↗
INTRODUCTION: Colitis is a colonic inflammatory reaction induced by various factors, such as pathogenic microorganisms, physical and chemical factors, and food allergens. At present, the mechanism of colonic motility dis...
INTRODUCTION: Colitis is a colonic inflammatory reaction induced by various factors, such as pathogenic microorganisms, physical and chemical factors, and food allergens. At present, the mechanism of colonic motility disorder in colitis remains unclear. The aim of the present study was to investigate the relationship between the expression of cystathionine γ-lyase (CSE) in neurons from colonic tissue and colonic motility disorders in colitis. METHODS: A model of colitis was established in rats. The disease activity index (DAI) was determined in the colitis model and control rats, and the number of fecal droppings was recorded for 7 days. Organ bath recordings, immunohistochemistry, immunocytochemistry, and Western blotting were performed on rat colonic samples and in neurons of the myenteric plexus of the enteric nervous system (ENS) in order to investigate the relationship between the expression of CSE and colonic motility disorder in colitis. RESULTS: In the colitis model, colonic motility and the number of fecal pellets were reduced. In addition, treatment with acetylcholine increased the contractile activity of colonic strips in both groups. Treatment with inhibitors of hydrogen sulfide (HS)-producing enzymes significantly increased the area under the curve of longitudinal muscle strips in the colitis group. CSE was expressed in the mucosa, submucosa, circular muscle, longitudinal muscle cells, and myenteric plexus. The expression of CSE in neurons of the myenteric plexus of the ENS was upregulated in the colitis group. CONCLUSION: These findings suggest that upregulation of endogenous HS synthetase and increased HS production may account for decreased colonic motility.
Endoscopic Treatment of Achalasia.
Latorre G, Bechara R
Digestion · 2025 · PMID 40435992 · Publisher ↗
BACKGROUND: Achalasia is the most common major esophageal motility disorder, characterized by impaired lower esophageal sphincter relaxation and absent or ineffective peristalsis. Peroral endoscopic myotomy (POEM), pneum...
BACKGROUND: Achalasia is the most common major esophageal motility disorder, characterized by impaired lower esophageal sphincter relaxation and absent or ineffective peristalsis. Peroral endoscopic myotomy (POEM), pneumatic dilation, and botulinum toxin injection are the main endoscopic therapies available. This review highlights recent advances, technical variations, and updated evidence on the efficacy and safety of POEM. SUMMARY: POEM has emerged as a highly effective and minimally invasive treatment for achalasia, with randomized controlled trials demonstrating excellent long-term clinical success and durability. Its safety profile and capacity for a tailored myotomy offer distinct advantages over alternative therapies. However, gastroesophageal reflux disease (GERD) remains a key concern. Ongoing efforts are focused on optimizing procedural techniques, including myotomy length and orientation, sling fiber preservation, and the addition of fundoplication. Additionally, training protocols, patient selection criteria, and strategies to prevent and predict GERD are critical areas of development. Future research should aim to refine follow-up strategies and define objective measures of success to enhance the safety, efficacy, and accessibility of POEM. KEY MESSAGES: Endoscopic treatments of achalasia, particularly POEM, offer effective and durable outcomes. Optimizing technique, refining training, and managing GERD are essential for improving safety and long-term success.
Steatotic Liver Disease Subtypes and Their Association with Colorectal Cancer Risk in Korea: A Nationwide Population-Based Study.
Moon SY, Son M, Lee JY … +2 more , Kang YW, Koh M
Digestion · 2025 · PMID 40435943 · Publisher ↗
INTRODUCTION: A recent Delphi consensus proposed a new classification system for steatotic liver disease (SLD), replacing the previous terminology, non-alcoholic fatty liver disease. This study aimed to examine the assoc...
INTRODUCTION: A recent Delphi consensus proposed a new classification system for steatotic liver disease (SLD), replacing the previous terminology, non-alcoholic fatty liver disease. This study aimed to examine the association between SLD subtypes and the risk of developing colorectal cancer (CRC). METHODS: We used the Korean National Health Insurance Service database to identify participants who underwent health screenings in 2009 and 2010 and retrospectively analyzed their data through to 2019. The participants were grouped into four categories: no SLD, metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-related liver disease (ALD). Hepatic steatosis was defined as a fatty liver index ≥30. The primary outcome was the occurrence of newly diagnosed CRC according to the SLD classification. RESULTS: This analysis included 242,275 participants. The adjusted hazard ratios for CRC incidence were 1.17 (95% confidence interval [CI]: 1.10-1.25) for MASLD, 1.45 (95% CI: 1.28-1.65) for MetALD, and 1.78 (95% CI: 1.48-2.14) for ALD, with no SLD as the reference group. All results were statistically significant (p < 0.001). CONCLUSION: Individuals in Korea with MASLD, MetALD, or ALD are at an increased risk of developing CRC.
High-Fat Diet-Induced Gut Microbiota Disruption Promotes Colorectal Cancer Lymphatic Metastasis via Propionate/GPR41 Signaling.
Wang J, Tan Q, Ni M … +6 more , Chen F, Yang J, Wang G, Zhao X, Zhang X, Zhang S
Digestion · 2025 · PMID 40435940 · Publisher ↗
INTRODUCTION: High-fat diets (HFDs) are known to affect the gut microbiome structure and potentially promote the development and metastasis of colorectal cancer (CRC). This study aims to elucidate the molecular mechanism...
INTRODUCTION: High-fat diets (HFDs) are known to affect the gut microbiome structure and potentially promote the development and metastasis of colorectal cancer (CRC). This study aims to elucidate the molecular mechanisms through which gut microbiome dysbiosis, mediated by the propionate/GPR41 signaling pathway, promotes lymphangiogenesis and lymph node (LN) metastasis in CRC, providing new insights for CRC treatment. METHODS: Microbial diversity and composition in rectal cancer were compared between CRC patients and healthy controls using 16S rRNA sequencing. Key genes related to short-chain fatty acid metabolism, HFD, and gut microbiota were identified. In vitro assays assessed CRC cell proliferation, migration, invasion, and lymphangiogenesis. A CRC mouse model on an HFD was used to measure fecal propionate levels and analyze GPR41 expression in tumors. In vivo fluorescence imaging was employed to track cancer cell migration and lymph node metastasis. RESULTS: HFD-induced microbial dysbiosis led to a significant reduction in SCFA-producing bacteria and an increase in proinflammatory species. This dysbiosis contributed to the suppression of propionate's protective effects. Propionate inhibited CRC cell proliferation, migration, and invasion under HFD conditions by activating the GPR41 pathway. Silencing GPR41 reversed these inhibitory effects, highlighting the key role of GPR41 in mediating propionate's antitumor effects. In vivo experiments further confirmed that propionate suppressed HFD-enhanced CRC lymphatic metastasis through the GPR41 signaling pathway, linking microbial dysbiosis with the modulation of cancer progression. CONCLUSION: This study reveals that HFD promotes CRC lymphangiogenesis and LN metastasis through gut microbiota dysbiosis and suppression of the propionate-activated GPR41 signaling pathway. These findings highlight the therapeutic potential of targeting the propionate/GPR41 axis, offering a promising strategy for developing novel anticancer therapies.
Biodegradable Stents for the Treatment of Refractory Benign Esophageal Strictures: Systematic Review and Meta-Analysis.
Tyč D, Vaněčková N, Hanuš J … +1 more , Selke Krulichová I
Digestion · 2025 · PMID 40425006 · Full text
UNLABELLED: <p>Introduction: Refractory benign esophageal strictures (RBES) pose significant clinical challenges. Biodegradable (BD) stents have emerged as alternatives to traditional stenting methods, offering the possi...
UNLABELLED: <p>Introduction: Refractory benign esophageal strictures (RBES) pose significant clinical challenges. Biodegradable (BD) stents have emerged as alternatives to traditional stenting methods, offering the possibility of reducing the need for multiple procedures. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of BD stents in the treatment of RBES. METHODS: The PubMed, Web of Science, Scopus, Cochrane, and Science Direct databases were searched according to the PRISMA statement. Studies that focused on the clinical outcomes of BD stents used in adult patients with RBES were included. Data on technical success and complication rates were analyzed using random-effects models. Efficacy data were analyzed using Kaplan-Meier analysis. RESULTS: The review included 15 studies with 241 BD stent implantations. The technical success rates were consistently high in all studies. The median time to restenosis was 21 weeks, with survival rates of 38.4% at 26 weeks and 27.0% at 52 weeks. The rate of complications requiring intervention was relatively low, but significant hyperplasia and pain occurred in 16.4% and 8.8% of the cases, respectively. Significant heterogeneity was observed in hyperplasia-related outcomes, which required a detailed subgroup analysis to investigate the underlying causes. CONCLUSION: BD stents provide acceptable results in terms of efficacy and safety for the treatment of RBES. However, the evidence is limited owing to the lack of randomized controlled trials and comparative studies. Future research should focus on these areas to strengthen the clinical evidence regarding BD stents. </p>.
Identification of <italic>GALNT12</italic> as a Novel Potential Diagnostic and Prognostic Marker for Esophageal Squamous Cell Carcinoma by Integrated Bioinformatics Analysis.
Chen Z, Kang L, Yang Z … +4 more , Cai Y, Yu S, Li P, Song J
Digestion · 2025 May · PMID 40334654 · Publisher ↗
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is a highly fatal cancer with unclear molecular underpinnings. This study utilized bioinformatics to uncover key genes and pathways associated with ESCC and to iden...
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is a highly fatal cancer with unclear molecular underpinnings. This study utilized bioinformatics to uncover key genes and pathways associated with ESCC and to identify prognostic markers. METHODS: We identified the differentially expressed genes (DEGs) using three datasets (GSE53625, GSE67269, and GSE23400-GPL96). Meanwhile, weighted gene co-expression network analysis (WGCNA) constructed gene co-expression networks based on the GSE23400-GLP97 dataset. Machine-learning algorithms further identified the most critical genes. Additionally, we validated the expression and diagnostic potential of the hub genes using the GSE161533 and GSE38129 datasets. Survival analysis and Gene Set Enrichment Analysis (GSEA) revealed the prognostic value and potential functions of the hub genes, respectively. RESULTS: The study identified 240 DGEs (103 upregulated and 137 downregulated). Concurrently, WGCNA pinpointed 209 genes associated with ESCC. Subsequently, machine-learning algorithms identify four hub genes, including KIF14, GALNT12, MGLL, and EMP1. Moreover, their expression differences and potential as diagnostic biomarkers for ESCC were validated. Survival analysis indicated that elevated GALNT12 expression was associated with a poor prognosis for ESCC patients. GSEA delineated the involvement of GALNT12 in critical biological pathways. CONCLUSION: Our results identified GALNT12 as a novel potential diagnostic and prognostic marker for ESCC.
Investigation of Recognition Areas by Explainable Artificial Intelligence for Colonoscopy Images of Irritable Bowel Syndrome.
Mihara H, Mihara H, Kuraishi S … +3 more , Fujinami H, Ando T, Yasuda I
Digestion · 2025 · PMID 40300572 · Full text
UNLABELLED: <p>Introduction: Irritable bowel syndrome (IBS) is a condition in which gastroenterological endoscopists cannot detect anomalies using colonoscopy, yet an artificial intelligence (AI) developed for IBS colono...
UNLABELLED: <p>Introduction: Irritable bowel syndrome (IBS) is a condition in which gastroenterological endoscopists cannot detect anomalies using colonoscopy, yet an artificial intelligence (AI) developed for IBS colonoscopy images has been able to distinguish between IBS and healthy individuals with high accuracy. However, it was unclear which areas the AI identified as abnormal. The aim of this study was to elucidate how AI identifies regions typical of IBS by constructing an additional explainable AI (XAI). METHODS: Colonoscopy images of healthy individuals, patients with constipation-predominant IBS, and patients with diarrhea-predominant IBS, which are available in a repository (<ext-link ext-link-type="doi" xlink:href="https://doi.org/10.5061/dryad.9s4mw6mkp" xmlns:xlink="http://www.w3.org/1999/xlink">https://doi.org/10.5061/dryad.9s4mw6mkp</ext-link>), were used. After setting up a Python environment on a local PC, the XAI models for the three groups were developed. Images not used in the AI construction were then evaluated using XAI. XAI-generated images were independently assessed by two evaluators, H.M. and S.K., to record and reconcile the characteristic differences among the three groups. RESULTS: Images correctly identified as those of healthy individuals by XAI were evaluated as characteristics over the entire image. By contrast, for IBS, only parts of the images were evaluated as characteristic regions. For diarrhea-predominant IBS, regions characterized by clear vascular boundaries, homogeneity or erythematous tones, or narrow and somewhat dark-appearing sections of the intestinal tract were identified. For constipation-predominant IBS, regions characterized by unclear vascular boundaries, faded tones, or dark sections where the end was not visible were identified. CONCLUSION: An XAI for IBS was collaboratively developed by endoscopists and clinical engineers, enabling the visualization of regions characteristic of IBS and healthy individuals. The real-time display of XAI is expected to further advance the elucidation of IBS pathophysiology. </p>.
Metagenomics Study Suggests the Role of Vitamins and Gut Microbiome in Autism Spectrum Disorder.
Komijani M, Mahdi ES, Komijani M … +1 more , Alaghmand A
Digestion · 2025 · PMID 40300566 · Publisher ↗
INTRODUCTION: Autism is a neurological disability that often appears after the age of three in children, also known as an autism spectrum disorder (ASD). Several studies have examined the influence of some environmental...
INTRODUCTION: Autism is a neurological disability that often appears after the age of three in children, also known as an autism spectrum disorder (ASD). Several studies have examined the influence of some environmental factors, and many parameters related to the behavior of autistic patients have been measured in order to find ways to reduce ASD. This study investigates the relationship between ASD and serum levels of vitamin D3, B12, folic acid, and the gut microbiome. METHODS: The serum levels of vitamin D3, B12, and folic acid in ASD patients were measured by the ELISA method and compared to healthy groups. DNA was extracted from stool samples of ASD patients and the control group, and then the gut microbiome was investigated via a metagenomics approach. Metagenomics sequencing was performed to analyze the 16S rRNA gene sequencing for phylum and sub phylum level microbiome. RESULT: The result showed no significant change in the VitD3 and folate levels of ASD patients compared to the control group (p = 0.157 and p = 0.0505, respectively). There was a significant difference in the VitB12 level between control healthy individuals and ASD patients, in which the serum VitB12 concentration was significantly lower than the control group (p = 0.0001). Our results regarding gut metagenomics showed that the abundance of the Actinobacteria by the phylum level was significantly higher in the ASD patients compared to the control group (p = 0.0013). The abundance of the Firmicutes by the phylum level was significantly lower in the ASD patients compared to the control group (p = 0.0016). The abundance of Bifidobacteriaceae, and Ruminococcaceae by the family level was significantly higher in the ASD patients compared to the control group (p = 0.0004 and p = 0.0489, respectively). Our results indicated less species richness in the ASD patients compared to the control group. CONCLUSION: Patients with ASD have lower serum levels of vitamin B12 and different gut microbiome compared to healthy controls. Low vitamin B12 levels and altered gut microbiome are significantly associated with ASD in this study. However, further research is needed to determine whether these factors could serve as predictors of severe outcomes in ASD.
Identification and Verification of B4GALNT2 as an Epigenetic Marker in Ulcerative Colitis.
Zhu Y, Zhu Y, Zhou Y … +4 more , Jiang H, Chen Z, Lu B, Wu J
Digestion · 2025 · PMID 40267892 · Publisher ↗
INTRODUCTION: Ulcerative colitis (UC) represents an inflammatory bowel disease characterized with a multifaceted pathogenesis, which may be attributed to influence by genetic factors. This study aimed to identify and val...
INTRODUCTION: Ulcerative colitis (UC) represents an inflammatory bowel disease characterized with a multifaceted pathogenesis, which may be attributed to influence by genetic factors. This study aimed to identify and validate novel markers associated with UC, with a specific focus on their regulation through DNA methylation. METHODS: Gene expression and DNA methylation profiling of intestinal mucosal tissues from UC and healthy controls was retrieved from the GEO repository. Differentially expressed and methylated genes were examined in UC. Subsequently, overlapped analyses were performed to identify highly expressed and hypomethylated genes, as well as lowly expressed and hypermethylated genes. Functional annotation, transcription factor-mRNA network analysis, and protein-protein interaction (PPI) network analysis were conducted for above genes. Dextran sodium sulfate (DSS)-induced LOVO and Caco-2 cells were established to stimulate UC injury. The expression and methylation of B4GALNT2 was verified by real-time quantitative polymerase chain reaction and methylation-specific PCR. Cell Counting Kit-8, flow cytometry, Western blot, and enzyme-linked immunosorbent assay were used to measure cell survival, apoptosis, and cytokine levels after B4GALNT2 overexpression. RESULTS: Our study screened 1 downregulated and hypermethylated gene (B4GALNT2) and 114 upregulated and hypomethylated genes in UC. They were markedly associated with immune response. Totally, 10 potential transcription factors were predicted. The PPI network revealed their complex interactions. B4GALNT2 was confirmed to be downregulated and hypermethylated in DSS-induced intestinal epithelial cells and in DSS-induced UC mouse model. B4GALNT2 overexpression enhanced cell viability and weakened apoptosis and cytokine production and release of DSS-induced intestinal epithelial cells. CONCLUSION: Collectively, this study integrally analyzed DNA methylation and gene expression in UC as well as identified and verified B4GALNT2 as a key epigenetic marker.
A New Anti-Parietal Cell Antibody Titer Measurement Kit for Diagnosis of Autoimmune Gastritis.
Ito M, Ito M, Maruyama Y … +5 more , Terao S, Okubo K, Hidaka K, Sakamoto T, Haruma K
Digestion · 2025 · PMID 40222358 · Full text
UNLABELLED: <p>Introduction: Recent findings revealed that autoimmune gastritis (AIG) is not rare in Japan. Therefore, the accurate diagnosis of AIG is essential in upper gastrointestinal practice. Diagnostic criteria fo...
UNLABELLED: <p>Introduction: Recent findings revealed that autoimmune gastritis (AIG) is not rare in Japan. Therefore, the accurate diagnosis of AIG is essential in upper gastrointestinal practice. Diagnostic criteria for AIG were established in 2023; however, the conventional fluorescent antibody (FA) method for anti-parietal cell antibody (APCA) titer measurements has low accuracy and is clinically problematic. METHODS: We developed a latex agglutination (LA) method using a new human-derived antigen. Samples subjected to measurements were sera from AIG cases (127 cases, 49 males, average age 65.9 years) and control cases (129 cases, 81 males, average age 66.1 years) provided by the main facility and three affiliated facilities in Japan. APCA in whole serum was measured using the FA and LA methods. RESULTS: The diagnostic ability of AIG using the FA method was as follows: sensitivity of 99.2%, specificity of 41.1%, and an overall agreement rate of 69.9%, with low specificity previously being reported. On the other hand, the new LA method had good diagnostic performance with a sensitivity of 93.7%, a specificity of 95.4%, and an overall agreement rate of 94.5%. CONCLUSION: We developed a new APCA measurement system that will contribute to the accurate diagnosis of AIG. The use of this measurement system in clinical practice will facilitate the diagnosis and treatment of AIG. </p>.
Factors Contributing to the Efficacy of Fecal Microbiota Transplantation for Diarrhea-Dominant Functional Bowel Disorders.
Yamane T, Masaoka T, Ishii C … +7 more , Masuoka H, Suda W, Kurokawa S, Kishimoto T, Mikami Y, Fukuda S, Kanai T
Digestion · 2025 · PMID 40209695 · Publisher ↗
INTRODUCTION: In cases of effective fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), donor feces have been observed to be enriched in Bifidobacterium spp. Moreover, FMT for functional bowel dise...
INTRODUCTION: In cases of effective fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), donor feces have been observed to be enriched in Bifidobacterium spp. Moreover, FMT for functional bowel disease can improve psychiatric symptoms. Although intestinal dysbiosis has received attention as one of the pathophysiologies of IBS, the efficacy of FMT for IBS has not yet been established. In this study, we performed a post hoc analysis of the efficacy of FMT, focusing on metabolites in donor feces. METHODS: FMT was performed in 12 patients, 8 with refractory diarrhea-predominant IBS and 4 with functional diarrhea (FDr), who were refractory to medical therapy. The donors were family members within a second degree of kinship and differed for each transplant. Fecal characteristics were evaluated before and 12 weeks after transplantation using the Bristol stool scale (BS). BS scores of 3-5 at 12 weeks after transplantation were considered to indicate responders, while BS scores of 6 and 7 indicated nonresponders. Metagenomic and metabolomic analyses of all 12 donor fecal samples were performed to compare the responder and nonresponder groups. RESULTS: Before transplantation, all patients had BS scores of 6-7, but 12 weeks after transplantation, 6 were considered responders and 6 were nonresponders. Metagenomic analysis showed that effective donor feces contained significantly higher levels of Prevotella than did the ineffective donor feces. Metabolomic analysis showed that effective donor feces contained significantly higher levels of propionate and butyrate and significantly lower lactate levels than did ineffective donor feces. CONCLUSION: Propionate-, butyrate-, or Prevotella-rich donor feces may contribute to successful FMT in patients with diarrhea-dominant functional gastrointestinal disorders.
Association between Microbiome Dysbiosis and Postoperative Disorders before and after Gastrectomy.
Tanaka T, Fujii T, Takahashi H … +10 more , Kuramitsu K, Funasaka K, Ohno E, Akimoto S, Nakauchi M, Shibasaki S, Uyama I, Hirooka Y, Suda K, Tochio T
Digestion · 2025 · PMID 40203813 · Publisher ↗
INTRODUCTION: Gastrectomy considerably affects the gut microbiome; however, the association between dysbiosis and post-gastrectomy syndrome remains to be explored. This study prospectively explored fecal gut microbiota a...
INTRODUCTION: Gastrectomy considerably affects the gut microbiome; however, the association between dysbiosis and post-gastrectomy syndrome remains to be explored. This study prospectively explored fecal gut microbiota alterations following gastrectomy, investigating their potential association with weight loss. METHODS: The gut microbiome of 21 patients with gastric cancer scheduled for gastrectomy in April-October 2022 was analyzed using 16S rRNA gene next-generation sequencing. Stool and blood samples were collected before and 3 months after gastrectomy. The microbiome profiles were compared to those of 85 healthy controls. Bacterial taxa demonstrating significant changes were determined using the linear discriminant analysis effect size algorithm and further analyzed for their relationship with weight loss in the gastrectomy cohort. RESULTS: Postoperative complications (≥grade 2) were observed in 14.3% of patients. Postoperative weight loss was -10.9%, with the following breakdown: distal (-7.0%), total (-13.5%), and proximal (-14.0%) gastrectomy (p = 0.003). Microbiota analysis demonstrated a significant incline in the abundance of the Streptococcus salivarius group and a decline in Bacteroides uniformis in patients with gastric cancer compared to healthy controls. The S. salivarius group exhibited a further increase, while B. uniformis showed signs of recovery after gastrectomy. Additionally, 5α-reductase gene levels, reported to decrease as several cancers progress, were found to elevate post-surgery. Furthermore, patients experiencing greater weight loss showed a significant reduction in Faecalibacterium prausnitzii levels, while lower serum prealbumin and zinc levels were associated with the abundance of Escherichia coli. CONCLUSION: Gastrectomy significantly alters the gut microbiome. Supporting microbiome health with prebiotics may help alleviate postoperative issues and improve patients' quality of life.
KIF4A Facilitates Oxaliplatin Resistance and Stemness in Colon Cancer by Boosting Glucose Metabolism.
Wang J, Cai C, Zhang X … +7 more , Ge C, Zhou S, Jin Z, Dai K, Dai N, Yu X, Wang J
Digestion · 2025 · PMID 40147432 · Publisher ↗
INTRODUCTION: Colon cancer (CC) is a malignant tumor commonly found in the intestines with high incidence and mortality rates. Oxaliplatin (OXA) is a platinum-based chemotherapy drug widely used to treat CC. However, fre...
INTRODUCTION: Colon cancer (CC) is a malignant tumor commonly found in the intestines with high incidence and mortality rates. Oxaliplatin (OXA) is a platinum-based chemotherapy drug widely used to treat CC. However, frequent drug resistance in patients results in suboptimal treatment outcomes. Though kinesin family member 4A (KIF4A) has been reported to be upregulated in various cancers and linked with poor prognosis in patients, its regulatory mechanism in cellular metabolism remains unclear. METHODS: The human CC/OXA-resistant cell line (HCT116-R) was constructed. CCK-8 assay was employed to calculate the half-maximal inhibitory concentration (IC) of CC cells. The level of cell stemness was assessed by cell sphere formation assay. The enrichment of KIF4A in signaling pathways of CC was analyzed through Gene Set Enrichment Analysis (GSEA). The bioinformatics analysis was applied to reveal the differential expression of KIF4A in CC and its correlation with genes related to stemness or glycolysis. The assessment of lactate in the supernatant was finished by utilizing the lactate detection kit. The oxidative phosphorylation and glycolysis levels in cells were measured by a Seahorse analyzer. The mRNA expression level of KIF4A was detected by quantitative real-time PCR. Furthermore, the Western blot (WB) was employed to determine the protein expression of glycolysis-related enzymes in cells. A mouse OXA-resistant CC xenograft tumor model was established, with changes in tumor volume and final weight recorded. TUNEL was utilized to detect the apoptosis level in tissues and immunohistochemistry to examine the distribution of KIF4A and ki-67 in tissues. The levels of stemness-related proteins in tissues were detected through WB. RESULTS: KIF4A was upregulated in CC, exhibiting a positive association with OXA resistance. High expression of KIF4A promoted cancer cell survival and cancer stemness. In GSEA prediction, KIF4A in CC may be linked with the glycolysis pathway. Correspondingly, the expression of KIF4A in CC was positively correlated with the expression of glycolysis-related proteins. Tests for lactate content and glycolysis/oxidative phosphorylation levels revealed that knocking down KIF4A repressed glycolytic function in the drug-resistant strain but reinforced mitochondrial oxidative phosphorylation. Furthermore, KIF4A overexpression effectively boosted the OXA resistance and stemness of cells, which was reversed by glycolysis inhibitor. The mouse model validated the above results. CONCLUSION: KIF4A is significantly upregulated in CC to reinforce the glycolysis of cancer cells, thus facilitating cell stemness and resistance to OXA-based therapy.
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