Introduction

Recurrent bile duct stones (RBDS) develop in up to 20% of patients after successful endoscopic clearance of initial stones. While anatomical and procedural risk factors are well recognized, the role of bile acid composition and bile microbiota in RBDS has gained attention. Bile acids, critical for cholesterol solubilization and intestinal homeostasis, may undergo deconjugation or biotransformation when exposed to intestinal flora via duodenobiliary reflux, altering their physicochemical properties and promoting lithogenicity.

Aims & Methods

We aimed to investigate whether alterations in bile acid composition and microbial colonization are associated with stone recurrence. A total of 184 patients who underwent biliary drainage at Konyang University Hospital (2019–2022) were enrolled. Patients were categorized into First Diagnosis Group (n=155) and Recurrence Group (n=29). Bile was aspirated after ERCP or PTBD, and 15 bile acids (5 unconjugated, 10 conjugated) were quantified using HPLC-MS/MS. Bile cultures were analyzed for microbial composition. Statistical comparisons were made using independent t-tests and chi-square analysis.

Results

Patients with RBDS were significantly older (77.8 vs. 69.0 years, P=0.005). Total bile acid concentration was lower in the Recurrence Group (4734 vs. 5902 ppm, P=0.083). Conjugated bile acids—including T-CA, T-DCA, G-CA, G-DCA, and G-LCA—were significantly reduced (P<0.05). Taurine-conjugated bile acids showed a marked decline (1326 vs. 1876 ppm, P=0.041). Primary bile acids were lower in the Recurrence Group (3272 vs. 4339 ppm, P=0.035), while the primary-to-secondary bile acid ratio was significantly decreased (3.29 vs. 7.35, P=0.001), indicating a shift toward hydrophobic bile.
Microbiologically, Enterococcus spp. were significantly more prevalent in the Recurrence Group (76% vs. 30%, P<0.001), particularly E. faecalis, E. casseliflavus, and E. gallinarum. Notably, E. faecalis possesses bile salt hydrolase (BSH) activity that can deconjugate bile acids, promoting accumulation of hydrophobic, poorly soluble forms. This aligns with the observed increase in unconjugated LCA and DCA.

Conclusion

Recurrent bile duct stone patients exhibit reduced levels of conjugated and primary bile acids and increased prevalence of bile-resident Enterococcus spp., known for bile salt hydrolase activity. These changes may lead to deconjugation, increased hydrophobicity, and impaired micelle formation, contributing to bile lithogenicity. These findings support the potential utility of bile acid profiling and bile microbiota analysis as predictive and preventive tools in RBDS management.

References

1. Hofmann AF, Mysels KJ. Bile acids as biological surfactants. Colloids Surf. 1987;30(1):145–173.
2. Begley M, Hill C, Gahan CG. Bile salt hydrolase activity in probiotics. Appl Environ Microbiol. 2006;72(3):1729–1738.
3. Choe JW, Lee JM, Hyun JJ, Lee HS. Analysis on microbial profiles and components of bile in patients with recurrent CBD stones after endoscopic removal: a preliminary study. J Clin Med. 2021;10(15):3303.
4. Ryu KH. Gut Microbiota and Pancreatobiliary System. Korean J Gastroenterol. 2020;75(5):231–239. (Korean)
5. Di Ciaula A, Garruti G, Baccetto RL, Molina-Molina E, Bonfrate L, Portincasa P. Bile acid physiology. Ann Hepatol. 2018;16(1):4–14.
6. Wang DQ, Cohen DE, Carey MC. Biliary lipids and cholesterol gallstone disease. J Lipid Res. 2009;50 Suppl:S406–S411.

Introduction

Colorectal cancer, the third most prevalent malignancy globally[1], exhibits strong associations with aberrant DNA methylation patterning. While DNA methyltransferase inhibitors (DNMTis) demonstrate therapeutic efficacy in hematologic malignancies, their clinical application in solid tumors remains constrained by dose-limiting genomic instability secondary to genome-wide hypomethylation[2]. Recent mechanistic studies have established methyl-CpG-binding domain protein 2 (MBD2) as a pivotal mediator of methylation-dependent transcriptional repression; however, its potential involvement in context-dependent oncogene activation remains unresolved. This study elucidates that pharmacological MBD2 inhibition achieves dual epigenetic rectification – reactivating tumor suppressor genes through promoter demethylation while selectively attenuating WNT16 overexpression via methylation-sensitive suppression, thereby establishing a targeted therapeutic paradigm that circumvents the pleiotropic toxicity associated with conventional DNMTis.

Aims & Methods

A multi-dimensional platform encompassing clinical specimens, cell lines, patient-derived organoids, and PDX models was employed. Integrative whole-genome bisulfite sequencing and RNA-seq analyses delineated methylation-driven transcriptional networks. Chromatin immunoprecipitation sequencing characterized MBD2 binding at differentially methylated regions, with CRISPR interference validating functional regulatory elements.

Results

CRC cells exhibited pronounced hypomethylation at the WNT16 promoter accompanied by diminished MBD2 occupancy. MBD2 inhibitor treatment downregulated WNT16 expression at both RNA and protein levels, concomitant with suppression of Wnt/β-catenin signaling. In PDX models, MBD2 inhibition reduced tumor burden without inducing genomic instability—a hallmark toxicity of conventional DNMTis.

Conclusion

This study unveils a novel epigenetic mechanism wherein MBD2 facilitates oncogenic WNT16 activation via its "methylation reader" function. Compared to broad-spectrum DNMTis, MBD2-targeted therapy achieves precise correction of carcinogenic epigenetic lesions while avoiding genome-wide hypomethylation risks, advancing a paradigm for targeted CRC treatment.

References

[1] Jiexi Li, Xingdi Ma, Deepavali Chakravarti, Shabnam Shalapour, Ronald A DePinho. Genetic and biological hallmarks of colorectal cancer. Genes Dev.
2021;35(11-12):787-820
[2] Marie Lopez, Julie Gilbert, Jean Contreras, Ludovic Halby, Paola B Arimondo. Inhibitors of DNA Methylation. Adv Exp Med Biol. 2022;1389:471-513
[3] Yang Xie, Feng Wang, Jun Yu, Jing Zhang, Yuting Liu, Mengying Li, Jian Qi. Silencing of MBD2 and EZH2 inhibits the proliferation of colorectal carcinoma cells by rescuing the expression of SFRP. Oncol Rep. 2021;46(6):250.

Introduction

The impact of antral preservation versus antral resection in sleeve gastrectomy remains a subject of debate due to its potential effects on weight loss, metabolic outcomes, and gastrointestinal function. This meta-analysis aims to provide a comparative assessment of these surgical techniques.

Aims & Methods

The Meta-Analysis aims to provide a comprehensive analysis between ​these two surgical techniques.
A systematic review and meta-analysis were conducted using 10 studies published between 2014 and 2025 that compared sleeve gastrectomy with antral preservation versus antral resection. The primary outcomes included excess weight loss (EWL) at different time points, while secondary outcomes assessed metabolic parameters (C-peptide, GLP-1, HbA1c), gastric emptying, gastroesophageal reflux disease (GERD), and resolution of comorbidities.

Results

A total of 10 studies were included. Patients undergoing antral resection exhibited greater excess weight loss at 6 and 12 months (MD: -4.50, 95% CI: -5.98 to -3.02; MD: -6.11, 95% CI: -7.74 to -4.47, respectively; p<0.00001), though the difference diminished by 24 months (MD: -3.37, 95% CI: -7.04 to 0.30; p=0.07). No significant differences were observed in overall GERD incidence (RR: 1.00, 95% CI: 0.75–1.33) or complications (RR: 1.00, 95% CI: 0.74–1.42). Metabolic outcomes showed marginal differences, with C-peptide (SMD: 0.02, 95% CI: -0.38 to 0.42) and GLP-1 (SMD: -0.22, 95% CI: -0.90 to 0.47) exhibiting minimal changes between groups.

Conclusion

Antral resection in sleeve gastrectomy is associated with superior short-term weight loss, but long-term differences remain inconclusive. Metabolic outcomes and postoperative complications appear comparable between techniques. Further randomized controlled trials with extended follow-up are warranted to refine surgical recommendations.

References

Disclosure

The author(s) declare no conflict of interest

Introduction

Graves’ disease (GD) and ulcerative colitis (UC) are two distinct autoimmune disorders with increasing evidence of shared pathophysiological mechanisms. While previous epidemiological studies have reported a higher risk of IBD among individuals with GD, the association between GD and UC specifically remains controversial. In particular, the causal direction, genetic liability, and molecular mediators underlying this relationship are not well defined.

Aims & Methods

We conducted a multi-layered investigation to clarify the relationship between GD and UC. First, a large-scale prospective analysis using the UK Biobank cohort was performed to assess the association between GD and subsequent UC risk, with adjustments for demographic, lifestyle, and clinical covariates utilizing COX proportional hazard models. Second, two-sample Mendelian randomization (MR) analyses were conducted using publicly available genome-wide association study (GWAS) datasets to infer potential causal links. Finally, we performed protein mediation analysis integrating plasma proteomic data to identify potential intermediate proteins and pathways mediating the effect of GD on UC.

Results

Observational analysis revealed that patients with GD had a significantly elevated risk of developing UC. Stratified analysis further revealed that this association was more pronounced among male and obese individuals. The association remained significant even after adjusting for key covariates including medication use, psychological disorders, air pollution exposure, and sunlight exposure. Genetic-level analysis using Mendelian randomization confirmed a potential causal relationship between AITD and UC. This association was independently validated in MR sensitivity analyses. Through mediation analysis based on plasma proteomic data, 28 UC-related proteins were identified as potential mediators of the AITD–UC relationship. Among them, proteins such as Arachidonate 15-lipoxygenase B (ALOX15B) were significantly enriched in the high-risk group. Collectively, six pathways likely represent the core signaling axes through which GD promotes UC pathogenesis, highlighting potential targets for mechanistic and therapeutic exploration.

Conclusion

This study provides robust clinical, genetic, and molecular evidence for a link from GD to UC, mediated through specific immunopathogenic proteins and pathways. These findings offer novel insights into shared autoimmunity and may inform biomarker-driven strategies for early identification and targeted prevention of UC in patients with GD.

References

Ferrari SM. The association of other autoimmune diseases in patients with Graves' disease (with or without ophthalmopathy): Review of the literature and report of a large series. Autoimmun Rev. 2019 Mar;18(3):287-292.
Ordás I. Ulcerative colitis. Lancet. 2012 Nov 3;380(9853):1606-19.
Xian W. Graves Disease and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization. J Clin Endocrinol Metab. 2023 Apr 13;108(5):1075-1083.
Burisch J. Incidence of Immune-Mediated Inflammatory Diseases Among Patients With Inflammatory Bowel Diseases in Denmark. Clin Gastroenterol Hepatol. 2019 Dec;17(13):2704-2712.e3.

Disclosure

The authors declare no conflicts of interest.