Introduction

Cholesterol is a key lipid involved in maintaining intestinal epithelial cell membrane structure and function. Recent studies suggest that microbiome-derived cholesterol metabolites, like ursodeoxycholic acid (UDCA) and 7-ketolithocholic acid (7-keto-LCA) promote intestinal epithelial repair and enhance Wnt signalling, thereby facilitating the self-renewal of intestinal stem cells (Li et al., Cell Host & Microbes 2024).

Aims & Methods

This study aimed to evaluate the effects of cholesterol-derived microbial metabolites—specifically lithocholic acid (LCA), deoxycholic acid (DCA), ursodeoxycholic acid (UDCA), and 7-keto-LCA—on intestinal epithelial barrier integrity, inflammatory responses, and homeostasis. Primary screening was conducted in Caco-2 monolayers co-treated with pro-inflammatory cytokines IFN-γ and TNF-α for 24 hours to mimic an inflammatory environment. Metabolites were tested at the following concentrations: LCA (10 µM, 50 µM, 75 µM), DCA (10 µM, 100 µM, 200 µM), UDCA (100 µM, 250 µM, 500 µM), and 7-keto-LCA (5 µM, 10 µM, 50 µM, 100 µM). Selected compounds showing significant effects were further validated in 3D intestinal epithelial organoid cultures. Gene expression analysis of key markers—TNF-α, CXCL9 (inflammation), OCLN, TJP1 (barrier integrity), and FGF19, NR0B2 (homeostasis)—was performed using quantitative RT-PCR. Statistical significance was determined using Student’s t-test with a threshold of p ≤ 0.05.

Results

Primary screening on Caco-2 cells revealed that 7-keto-LCA (10µM, 50µM) and LCA (75µM) downregulated the expression of genes encoding inflammatory cytokines (TNF-a and/or CXCL9; p < 0.05) and upregulated the expression of tight junction proteins (OCLN and TPJ1; p < 0.05) and FXR downstream marker (FGF19, p < 0.05). The tested concentrations of DCA and UDCA did not reduce the expression of inflammatory cytokine coding genes and reinstate the expression of tight junction proteins coding genes. For further analysis in 3D intestinal organoid model we selected 7-keto-LCA (10µM). 7-keto-LCA significantly upregulated the expression of NR0B2 (p < 0.05) and showed a tendency to reduce the expression of TNF-α in intestinal organoids (p = 0.12).

Conclusion

7-keto-LCA showed a trend to reduce inflammation and restore homeostasis in intestinal organoid model.
Study has been funded by the Research Council of Lithuania (LMTLT, agreement No. S-MIP-23-101).

References

Li T, Ding N, Guo H, Hua R, Lin Z, Tian H, Yu Y, Fan D, Yuan Z, Gonzalez FJ, Wu Y. A gut microbiota-bile acid axis promotes intestinal homeostasis upon aspirin-mediated damage. Cell Host Microbe. 2024 Feb 14;32(2):191-208.e9. doi: 10.1016/j.chom.2023.12.015.

Introduction

Artificial intelligence (AI) is increasingly integrated into medical decision-making and education, particularly through large language models such as ChatGPT. In gastroenterology, where clinical reasoning relies heavily on imaging, biological interpretation, and complex decision processes, the effective implementation of AI tools remains poorly documented in real-world settings.

Aims & Methods

This study aimed to compare how gastroenterologists and physicians from other specialties perceive the usefulness and practical applications of AI in gastroenterology, with a focus on diagnostic, therapeutic, and educational support.
A cross-sectional survey was distributed to physicians practicing in various hospital settings in March 2025. Participants were grouped as gastroenterologists or non-gastroenterologists. The questionnaire assessed demographics, clinical exposure to digestive diseases, prior AI usage, and perceived utility of AI in gastroenterology. Statistical comparisons were conducted using the Chi-squared test, with significance set at p<0.05.

Results

Gastroenterologists were significantly more likely to have used AI for gastroenterology-specific clinical questions (64% vs. 41% among other physicians). While 96% of all respondents acknowledged the potential usefulness of AI in gastroenterology, gastroenterologists expressed greater caution: 60% described AI as useful but with limitations, 36% viewed it as a promising tool, and 4% saw no particular benefit. Similar distributions were observed among other physicians (56%, 42%, and 2%, respectively), with no statistically significant difference in overall perception (p = 0.77).
However, the perceived domains of utility differed significantly between the groups (p = 0.047). Gastroenterologists most often highlighted the role of AI in continuing medical education (24.5%), diagnostic support (20.8%), and public education (15.1%). In contrast, other physicians emphasized diagnostic assistance (21.9%), pedagogical support (23.5%), and notably, therapeutic decision-making (13.8%), which was less frequently cited by gastroenterologists (7.5%).

Conclusion

Gastroenterologists—although more experienced with AI in their field—tend to adopt a more cautious and targeted perspective on its clinical integration. They see it as a complementary tool for interpretation and professional development, rather than a primary decision-making assistant. Meanwhile, non-specialist physicians show a slightly broader enthusiasm, seeing AI as helpful both in clinical decisions and educational support. While both groups recognize the potential of AI in gastroenterology, its successful implementation will require tailoring to the specific expectations, workflows, and trust levels of each medical discipline.

Introduction

Endoscopic scores are crucial for assessing Crohn's disease (CD) severity, guiding therapy, and monitoring progression. The Simplified Endoscopic Score for Crohn's Disease (SES-CD) is widely used for this purpose [1]. Accurate scoring is vital for patient care. Recently, artificial intelligence has demonstrated potential in medical image interpretation [2]. This study aims to evaluate ChatGPT's effectiveness in rating the SES-CD.

Aims & Methods

This retrospective study evaluated ChatGPT's accuracy in assessing CD endoscopic activity using the SES-CD. One representative still image was selected for each bowel segment, and stricture degrees were provided separately if present. ChatGPT scored the SES-CD based on these images. The IBD expert's ratings were validated by calculating the intra-class correlation coefficient (ICC) with clinical trial central readers. The ICC between the IBD expert and ChatGPT scores was calculated to determine ChatGPT's reliability in SES-CD scoring.

Results

Nine (mean age 32.0 ± 11.8 years, 77.8% male) were included, with 45 bowel segments. Three (33.4%), 5 (55.6%), and 1 (11.1%) had nonstricturing nonpenetrating, structuring, and penetrating disease, respectively. Four (44.4%) had ileal disease and 5 (55.6%) had ileocolonic disease. Five (55.6%) had previous IBD surgery.
The SES-CD scores of the participants, rated by IBD expert in the hospital, revealed the following mean and standard deviation for each segment of the bowel: 6.9 ± 2.3 in the ileum, 1.3 ± 2.6 in the right colon, 1.6 ± 2.4 in the transverse colon, 1.3 ± 2.6 in the left colon, and 1.3 ± 2.6 in the rectum. The total SES-CD score was 12.4 ± 10.9. The score reliability of the institute IBD expert was tested compared to the clinical trial central reader and an intraclass correlation coefficient was calculated and found to be 0.96 (95% CI, 0.84-0.99) which is considered extremely correlated.
The mean and standard deviation of ChatGPT score in each segment were: 6.4 ± 2.4 in the ileum, 2.4 ± 3.8 in the right colon, 0.9 ± 2.7 in the transverse colon, 0.3 ± 1.0 in the left colon, 0.6 ± 1.3 in the rectum, with total SES-CD score of 10.6 ± 6.8. The calculated ICC between the expert and ChatGPT obtained SES-CD scores was 0.80 (95% IC, 0.64- 0.89) which is considered highly correlated.

Conclusion

Despite being based on only one photo per segment, ChatGPT demonstrated satisfactory performance in estimating endoscopic activity in CD. The differences between the IBD expert obtained scores and ChatGPT scores were acceptable, suggesting that artificial intelligence has the potential to be a useful tool in clinical and research settings, providing an accurate estimation of disease severity based on limited visual data.

References

1- Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
2- Levartovsky A, Albshesh A, Grinman A, et al. Enhancing diagnostics: ChatGPT-4 performance in ulcerative colitis endoscopic assessment. Endosc Int Open. 2025;13:a25420943. Published 2025 Mar 14.

Introduction

Current therapeutic strategies for inflammatory bowel disease (IBD) remain limited, with clinical efficacy often falling short of expectations. Post-translational modifications play a pivotal role in IBD pathogenesis. This study aims to elucidate the functional significance of ubiquitination in IBD development and progression.

Aims & Methods

By analyzing colon RNA sequencing (RNA-seq) data from healthy and dextran sulfate sodium (DSS)-induced colitis mice, combined with RNA-seq datasets from healthy individuals and ulcerative colitis (UC) patients, we identified differential RNA expression levels of ATDC between healthy and inflammatory groups. Single-cell RNA sequencing (scRNA-seq) analysis further pinpointed the primary cell types exhibiting ATDC expression discrepancies. These findings were validated through immunohistochemistry, immunofluorescence, and western blot. Co-immunoprecipitation (Co-IP) assays and molecular docking simulations were employed to confirm and model the interaction between ATDC and PRMT5 in vitro. The role of ATDC in IBD pathogenesis was investigated using an ATDC-knockout (ATDC-KO) murine DSS model, with flow cytometry analyses delineating its impact on immune status.

Results

RNA-seq analysis revealed elevated ATDC mRNA levels in DSS-treated mice and UC patient intestinal tissues. scRNA-seq data indicated ATDC upregulation predominantly in the intestinal epithelial cells of UC patients. Protein-level upregulation of ATDC was further confirmed in both DSS mice and UC patient specimens. Lipopolysaccharide stimulation increased ATDC expression in Caco2 cells. Overexpression of ATDC in Caco2 cells, coupled with mass spectrometry, identified ATDC-PRMT5 binding, which was corroborated by Co-IP assays and molecular docking simulations. ATDC overexpression downregulated PRMT5 protein (but not mRNA) levels. In DSS models, PRMT5 expression was reduced compared to healthy controls; however, ATDC-KO mice exhibited PRMT5 upregulation and exacerbated colitis severity. Flow cytometry demonstrated an elevated Th17 cell proportion in ATDC-KO DSS mice relative to wild-type counterparts.

Conclusion

This study is the first to demonstrate the protective role of ATDC in colitis. ATDC attenuates colonic inflammation by promoting the degradation of PRMT5, thereby suppressing Th17 cell-mediated immune responses. Enhancing ATDC activity may represent a novel therapeutic strategy for mitigating colitis progression.

References

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Introduction

Fatigue is highly prevalent in patients with Inflammatory bowel disease (IBD)and associated with reduced quality of life. However, effective treatments for IBD fatigue are lacking.

Aims & Methods

We aimed to assess the real-world efficacy of modafinil – a stimulant medication – on fatigue in IBD patients. The was a prospective evaluation in a tertiary IBD centre in the UK. Adults with a confirmed diagnosis of IBD, who were fatigued for at least 6 months, were referred for fatigue evaluation using the Inflammatory Bowel Disease Fatigue Self-Assessment Scale (IBD-F). The IBD-F includes 5 questions scored 0-4 using a Likert scale to identify fatigue. Scores range from 0-20 and scores ≥11 denote severe fatigue.
After treating organic causes of fatigue (anaemia, B12 deficiency, hypothyroidism, mucosal inflammation) and excluding contraindications, patients with a baseline IBD-F score ≥11 were offered modafinil. Modafinil was started at 100mg daily and titrated in 100mg increments to a maximum of 400mg daily if needed. If unable to tolerate 100mg, dosage was reduced to 50mg.
Patients were followed up until week 12 or drug withdrawal. IBD-F scores were reviewed at 12 weeks and compared to baseline. A clinically significant fatigue improvement was a reduction in the IBD-F score ≥3¹. Any patient who withdrew drug before 12 weeks was regarded as having severe fatigue at follow up.
Descriptive statistics were presented as means with standard deviation [SD]. A paired t-test was used to assess change in IBD-F scores from baseline with 5% significance level used.

Results

Seventy-two patients (50% male) were included with a mean age of 38 (SD 11.1) years . Of these, 53 (74%) had Crohn’s and 19 (27%) had UC with a mean disease duration of 13.2 (10.4) years (Table 1). The cohort showed refractory disease with 23 (32%) of patients having used at least 3 biologics, 24 (33%) had a stoma and 41(57%) had at least one bowel resection. The most common total modafinil dose was 200mg. Dosages ranged from 50mg to 400mg per day.
Both UC (15.9 [SD 2.58]) and Crohn’s (15.0 [2.31]) had similar mean (SD) baseline IBD-F scores. After treatment with modafinil, there was a statistically significant improvement in mean IBD-F score from baseline 15.3 [SD 2.38] to 10.4 [SD 3.83] (p<0.0001). There was no difference in the score improvement between UC and Crohn’s p=0.29. No difference was observed between those with and without irritable bowel syndrome (p=0.35). At follow up, 53 (74%) had a clinically significant improvement in fatigue and 38 (53%) were no longer severely fatigued.
Nine patients (13%) reported side effects: headache (n=5), and anxiety, mood changes, nausea, and visual issues (n=1 each). Three patients withdrew before the 12 week follow up. No serious adverse events were recorded.

Table1

Conclusion

In this real-world evaluation, modafinil was associated with a statistically significant improvement in fatigue in patients with mostly refractory IBD. Modafinil was generally well tolerated. Randomised, placebo-controlled trials of modafinil for IBD fatigue are now warranted.

References

1 Nocerino A, Nguyen A, Agrawal M, Mone A, Lakhani K, Swaminath A. Fatigue in Inflammatory Bowel Diseases: Etiologies and Management. Adv Ther. 2020;37(1):97-112. doi:10.1007/s12325-019-01151-w