Clinical and Experimental Gastroenterology最新文献

Helicobacter pylori (H. pylori) is a human bacterial pathogen that causes one of the most common chronic bacterial infections worldwide. The microorganism has been classified by the International Agency for Research on Cancer as a Group I carcinogen. While the etiological link to gastric cancer is well established, the precise molecular and cellular mechanisms driving this transformation are highly complex and incompletely understood. Fundamentally, the infection results from the chronic presence of acute on chronic gastric mucosal inflammation. H. pylori pathogenicity is increased by bacterial virulence factors including the cytotoxin-associated gene A (CagA) and Vacuolating cytotoxin A (VacA) which may interfere with the host's cell communication and create a pro-tumorigenic microenvironment. Host microRNAs (miRNAs) may amplify these effects by modulating immune responses, enhancing oncogenic signalling. Despite the proven benefits of H. pylori eradication in reducing cancer risk, especially in high-incidence regions, rising antibiotic resistance and host-related variables impede its global implementation. Recent advances in genomics and multi-omics profiling potentially offer new opportunities for targeted prevention. Moreover, emerging evidence suggests H. pylori may also negatively influence immunotherapy outcomes, underscoring its broader relevance in cancer treatment planning. By synthesizing molecular insights, epidemiological trends, and clinical data, this narrative review examines the multifaceted pathways through which H. pylori contributes to gastric carcinogenesis, integrating current knowledge on microbial virulence, host signalling disruption, immune modulation, and epigenetic remodelling.

Background and aims: Liver cirrhosis development is often accompanied by dysbiosis of the intestinal flora. As an important component of the human intestinal microflora, Faecalibacterium prausnitzii plays an important role in maintaining the intestinal ecological balance. This study aimed to investigate the protective effect of F. prausnitzii on carbon tetrachloride-induced cirrhosis in rats and its effect on intestinal homeostasis.

Methods: A rat model of liver cirrhosis was generated via treatment with CCL4 and gavage with F. prausnitzii live bacterial solution. Samples of blood, liver, colon and feces were collected from the rats. Liver function, serum cytokine levels, liver and intestinal pathology, the fecal flora structure and liver transcriptomics were assessed in the rats.

Results: F. prausnitzii administration attenuates pathological damage to the liver in cirrhotic rats; reduces the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP) and direct bilirubin (DB) (p < 0.05, p < 0.01); increases the albumin (ALB) level (p < 0.05); downregulates the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-10, IL-1β (p < 0.05, p < 0.01) and interferon-gamma (IFN-γ) (p < 0.05); reduces damage to the intestinal mucosal structure in cirrhotic rats; and maintains the barrier function of the intestine. In cirrhotic rats, certain organisms exhibited a decrease in abundance, while others showed an increase.

Conclusion: F. prausnitzii administration had a protective effect on cirrhotic rats by effectively regulating the intestinal flora, enhancing the barrier function of the intestinal tract, inhibiting the inflammatory response of the liver, and delaying liver fibrosis. This study provides a theoretical basis for the clinical application of F. prausnitzii.

Objective: To identify active components of Modified Tongyou Decoction (MTD) acting on esophageal cancer (EC) cell autophagy and their potential targets on Akt/mTOR pathway via network pharmacology integrated with experimental validation in vitro.

Methods: Data mining of EC-related target genes was performed. Protein-protein interaction (PPI) network and core target analysis were conducted, followed by analysis of the relevant autophagy pathway. Active compound docking with key targets was performed. Medicated serum of MTD was prepared from Sprague-Dawley (SD) rats that received intragastric administration of low (LD), medium (MD), and high-dose (HD) MTD. Concentrations of the top active compounds in the serum were measured with HPLC. EC TE-1 cells were cultured in medicated serum. Autophagic acidic vesicles and autophagosomes were observed. Protein expression of autophagy-related and Akt/ mTOR pathway molecules was assayed. Protein expression of LC3 was determined. mRNA expression of Beclin-1 was measured.

Results: The top four active compounds were quercetin, baicalein, luteolin, and β-sitosterol. The top four targets were TP53, CTNB1, EGFR, and Akt. Akt and mTOR were intersecting molecules involved in the EC autophagy pathway. The top compounds co-targeted Akt equally. Concentrations of the top compounds in the medicated serum accounted for 14-15%. MD increased the fluorescence intensity of acidic autophagy vesicles. LD and MD promoted an increase in autophagosomes. HD strongly affected Beclin-1, LC3, Akt, and mTOR. MD inhibited protein expression of p62 but promoted LC3 fluorescence intensity. These three doses had equal effects on mRNA expression of Beclin-1.

Conclusion: MTD specifically promotes EC autophagy depending on multiple components and specifically targets Akt/mTOR signaling pathway. MTD shows clear activity in EC cell autophagy regulated by the Akt/mTOR pathway.

Perianal fistulizing Crohn's disease is a severe and disabling phenotype of Crohn's disease, affecting up to one-third of Crohn's patients. This phenotype can result in significant quality of life impairment in quality of life due to chronic pain, persistent perianal drainage, and the risk of fecal incontinence. The presence of a perianal fistula indicates a more aggressive disease course, often requiring more frequent and coordinated care. Optimal management relies on a multidisciplinary team, including gastroenterologists, colorectal surgeons, and radiologists, to address the complex interplay of medical and surgical needs. Medical therapy achieves durable remission in only about one-third of patients, necessitating surgical intervention for the majority, with patients arriving to the operating room with more advanced disease activity and longer duration of immunosuppression. For patients with refractory disease, mesenchymal stem cell (MSC) therapy has emerged as a promising option, with clinical remission rates of approximately 50-80% at 6-12 months and a favorable safety profile, notably without increasing the risk of incontinence compared to conventional surgery. However, there is no approved MSC product currently available for clinical use. Given the complexity and morbidity of fistulizing perianal Crohn's disease, a multidisciplinary approach focused on individualized, evidence-based therapy is essential for optimizing outcomes.

Background: Patients with Inflammatory Bowel Disease (IBD) are at an increased risk of developing colorectal cancer (CRC). While numerous studies have explored chemoprevention strategies in the general population, the specific roles of statins and aspirin in reducing CRC risk among IBD patients remain inconclusive.

Aim: This study aims to evaluate the effect of statins on CRC risk and investigates whether combining statins and aspirin further reduces CRC risk in this high-risk population.

Methods: We included 11,325 IBD patients from the Northwell Health Information Exchange (HIE) database (2008-2023). Demographic and clinical variables were collected. The primary endpoint was CRC development, while the secondary endpoint was the occurrence of any cancer. Multivariable logistic regression assessed the association between cancer development and statin use, adjusted for confounders. Subgroup analyses evaluated the combined effect of statins and aspirin compared to non-users and aspirin-only users. Statistical significance was defined as a p-value <0.05.

Results: Among 11,325 patients (mean age 65.1± 20.4 years, 54.5% females, 68% white), 2,809 (24.8%) used statins. Logistic regression analysis revealed that statin use was associated with lower odds of CRC, although it did not reach statistical significance (OR: 0.647, p = 0.0564). It was, however, significantly associated with a reduced risk of any cancer (OR: 0.630, p<0.0001). Furthermore, combining statins and aspirin significantly reduced the risk of CRC (OR: 0.163, p=0.0028) and any cancer (OR: 0.367, p<0.0001) compared to non-users. When compared to aspirin-only users, the statin-aspirin combination was associated with significantly lower odds of CRC (OR: 0.235, p=0.0289) and any cancer (OR: 0.522, p=0.0087).

Conclusion: Statins are associated with a reduced risk of any cancer and a potential reduction in CRC in patients with IBD. The combination of statin-aspirin demonstrates a significant and synergistic protective effect, supporting its potential role in chemoprevention strategies for this high-risk population.

There is a rising prevalence of pediatric inflammatory bowel disease (PIBD) worldwide. This article aims to explore the key issues in managing PIBD and attempts to propose evidence-based recommendations. We reviewed published literature on PIBD, including original research, systematic reviews, meta-analyses, consensus statements, and position papers. The databases searched were PubMed/MEDLINE, Cochrane Library, Web of Science, and Scopus, using terms related to inflammatory bowel disease, colitis, ulcerative colitis, Crohn's disease, children, adolescents, and pediatrics. The selected articles were critically appraised, summarised and incorporated into the review. PIBD presents multifaceted challenges. They include atypical presentations, very early onset cases, growth and nutritional challenges that affect linear development and pubertal progression, pharmacological management issues related to age-specific medication safety and efficacy and timing of surgical interventions. There are impacts on development; psychosocial burden challenges in education, social development, and family dynamics, all crucial in the future of the child. There are also limitations in access to PIBD services with personalised treatment approaches and challenges in transitional care. It is important to identify these unique challenges posed by PIBD and address them in a comprehensive manner in a multidisciplinary approach.

Objective: This study aimed to identify risk factors associated with colorectal adenomatous polyps in young adults (≤40 years) to support early prevention and screening strategies for colorectal cancer.

Methods: We conducted a study involving 805 young patients who underwent colonoscopy at the Endoscopy Center of The Fifth Affiliated Hospital of Zhengzhou University, China, from September 2023 to January 2025. Among them, 288 patients had at least one pathologically confirmed adenomatous polyp (cases), and 517 patients with no detected polyps served as controls. Data on demographics, lifestyle habits (smoking, alcohol use), metabolic parameters, and hematological indices were collected and analyzed.

Results: Several factors were significantly associated with an increased risk of adenomatous polyps, including male sex, hypertension, diabetes, smoking, alcohol consumption, elevated body mass index, and reduced high-density lipoprotein cholesterol (HDL-C). Multivariate analysis further identified hypertension, alcohol use, and higher red blood cell count as independent risk factors. Conversely, female sex and higher HDL-C levels were found to be protective.

Conclusion: The development of colorectal adenomatous polyps in young adults is strongly linked to modifiable risk factors such as hypertension and alcohol consumption, as well as elevated red blood cell counts. These findings highlight the importance of addressing cardiovascular and metabolic health, along with lifestyle modifications, in early screening and prevention programs for high-risk young individuals.

Despite the success of monoclonal antibody (mAb) therapies in treating inflammatory bowel disease (IBD), a persistent therapeutic ceiling remains. This comprehensive review explores emerging strategies to enhance the efficacy of mAb-based treatments. Key among these is the development of bispecific antibodies designed to simultaneously engage two cytokine targets, offering dual blockade of inflammatory pathways and the potential for synergistic effects. Co-formulation approaches, comprising two or more mAbs within a single therapeutic product, are also examined as a means of broadening immunologic coverage and streamlining delivery. Finally, advances in pharmacokinetic optimisation are discussed, including Fc region modifications, polyethylene glycol conjugation, albumin fusion, and glycoengineering, all aimed at reducing immunogenicity and extending half-life. Together, these strategies represent a path toward next-generation biologics with the potential to minimise current limitations in IBD treatment.

Purpose: Long-standing mucosal inflammation is suspected to be one of the main drivers of colitis-associated colorectal cancer (CA-CRC), but far from all colitis patients develop cancer. Non-neoplastic mucosa located distant from neoplastic lesions may harbour early molecular events of carcinogenesis. We hypothesise that patients with UC who have progressed to neoplasia (progressors) exhibit a distinct molecular profile of mucosal inflammation from non-progressors.

Patients and methods: We performed transcriptomic profiling of 143 mucosal biopsies from non-neoplastic colonic segments of 14 UC progressors and 30 UC non-progressors using the Agilent SurePrint G3 human gene expression 60K microarray. Subsequently, we carried out gene set ontology analyses. In addition, we assessed lymphocyte infiltration to the mucosa of biopsies taken adjacent to biopsies used for transcriptomic analysis by immunohistochemistry.

Results: Adjusting for molecular alterations associated with long disease duration, our findings revealed that UC Progressors' inflamed mucosa has a distinct gene expression profile of 529 significantly deregulated genes, eg LTB, CXCL13, CD19, C3 and CYP4F3. The profile was negatively enriched for biological processes (BPs) such as adaptive immune responses and complement system activity and positively enriched for processes related to detoxification. The negatively enriched BPs were supported by the presence of fewer infiltrating B cells and less lymphoid aggregates in the microenvironment of the inflamed mucosa of progressors.

Conclusion: The inflamed colonic mucosa from UC patients who have progressed to dysplasia or cancer has a different gene expression profile than that of UC non-progressors, suggesting lower levels of lymphoid organ-initiating and immune cell-attracting signals and fewer infiltrating immune cells to the mucosa. Consequently, progressors may lack the ability to mount sufficient adaptive immune responses necessary to counteract driving forces of malignant transformation in UC.

Objective: Although the diagnosis of irritable bowel syndrome (IBS) is based on clinical criteria, a colonoscopy is often performed to rule out alternative digestive disorders. The panenteric PillCam™ Crohn's capsule, which allows non-invasive examination of both the small bowel and the colon, may be an alternative investigation. We aimed to evaluate the feasibility of a strategy based on the panenteric capsule in combination with standard biological tests to exclude gastrointestinal disease in young adult patients with chronic abdominal symptoms suggestive of IBS as an alternative to the classical approach based on colonoscopy.

Design: Of 42 consecutive adults aged 18-50 years with symptoms consistent with IBS for more than 6 months, 33 were enrolled, and 27 received both routine biological tests, fecal calprotectin, panenteric capsule, and gastrointestinal endoscopies.

Results: All 21 lesions identified by the capsule in 15 patients were unrelated to digestive symptoms, as were the 11 lesions identified by colonoscopy in 7 patients, and all were of little or no clinical interest. In addition, one gastric ulcer and one gastric MALT lymphoma diagnosed only by systematic gastric biopsy were characterized by upper endoscopy. The capsule was preferred by all patients to the classical endoscopic procedures.

Conclusion: The diagnosis of IBS was not called into question in any of the patients explored. These preliminary results demonstrate the feasibility of a strategy based on the panenteric capsule in combination with standard biological tests to exclude gastrointestinal disease in young adult patients with chronic abdominal symptoms suggestive of IBS.