Introduction

Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection. A pool of healthy stool donors is essential for any FMT program. However, donor
recruitment is not easy due to screening failures and the commitment requested.

Aims & Methods

We aimed to report data from the first two years of stool donor screening, recruitment, and stool banking from the first public Italian FMT center. We prospectively collected data from donor screening questionnaires, laboratory evaluations, and donations. Donor screening has been performed according to the Italian Health Ministry regulation and the FMT European consensus FMT (1): potential donors, all aged below 50 years old, were initially screened for the presence of concomitant gastrointestinal and systemic diseases or for the anamnestic drugs intake or recent antibiotic intake. The subsequent clinical evaluation aimed at excluding at-risk conditions for infectious diseases, while the microbiological screening evaluated the colonization by potential pathogens. Bacterial counts in terms of aerobes and anaerobes concentration [colony forming unit (CFU)/mL] from aliquots of each frozen fecal material after aerobic samples preparation were assessed after 1 week and subsequently monthly until 18 months from the donation.

Results

Two hundred and 12 patients completed screening questionnaires. Of these, 29 (13.7%) were excluded for concurrent gastrointestinal symptoms (altered bowel habits) or diseases, 50 (23.6%) for concomitant systemic diseases, and 8 (3.8%) for antibiotic intake in the previous 6 months. Finally, of the 120 donors clinically evaluated, 79 (37.3%) were excluded for at-risk conditions for infectious disease (e.g., use of illegal drugs, risky sexual behavior, recent body tattoo, piercing, travel in tropical countries, healthcare workers, etc.). Among the remaining 41 donors microbiologically screened, 19 (9%) were excluded for pathogens or potential pathogens presence (6 pathogenic Escherichia coli, 1 Vancomycin-resistant Enterococci, 2 Helicobacter pylori, 1 Rotavirus, 1 Giardia, and 8 for other reasons). Finally, 22 subjects (10.4%) were suitable for donation. Among the 10 healthy donors actively donating stools (50% females), 6 were excluded for pathogens infections diagnosed during donation screenings after a median of 3 donations (3 pathogenic Escherichia coli, 1 Salmonella enterica, 1 Campylobacter jejuni, 1 Cryptosporidium). Among the remaining 4 subjects, 2 discontinued the donation program due to the commitment requested. Finally, 22 subjects (10.4%) were suitable for donation. Ten healthy donors actively donated stools (50% females), but 6 were excluded for pathogens/potentially pathogenic bacteria diagnosed during donation screenings after a median of 3 donations. Among the remaining 4 subjects, 2 discontinued the donation program due to the commitment requested.
Aliquots evaluation showed no differences in aerobic counts until 18 months, while significant differences were found for anaerobic counts already after 1 month (1.33x10^10 CFU/mL vs 7.6x10^9 CFU/mL at donation and after 1 month, respectively, p=0.028).

Conclusion

Only one in ten potential healthy donors is finally eligible for stool donation. Frozen stool samples showed a significant decrease in anaerobic concentration already after 1 month from storage, compared to fresh material.

References

1. Cammarota G., et al. Gut. 2017 Apr;66(4):569-580.

Disclosure

Lecture grants from EG Pharma, AlfaSigma, Bromatech, Echosens, Ferring, Mayoly Spindler and Schwabe Pharma.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

Inflammatory bowel disease (IBD) shares many features with other chronic inflammatory diseases (CIDs), such as rheumatoid arthritis and psoriasis, which are characterized by dysregulated immune responses and systemic manifestations. While IBD is primarily associated with inflammation in the gut, it can also lead to extra-intestinal symptoms, including joint pain and skin lesions, which are commonly observed in these other diseases. Understanding commonalities and differences among these chronic inflammatory conditions is important for developing more effective therapies that can target the underlying immune dysregulation and improve patients' overall quality of life.

Aims & Methods

We aim to identify both the common disease signatures shared between IBD and other CIDs, as well as the disease-specific signatures unique to each condition. A cross-sectional cohort of 650 patients with CIDs, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, psoriasis, and systemic lupus erythematosus (SLE), were recruited from the University Hospital Kiel. Peripheral blood samples were collected from this cohort, along with samples from 202 healthy controls, and subjected to RNA sequencing and methylation profiling. At the time of sample collection, the patients in the cohort underwent detailed clinical phenotyping including assessments of disease activity and symptoms. Additionally, these patients were followed up for up to 5 years to record any potential future complications that may arise.

Results

We performed differential expression and methylation analysis between each CID diagnosis and the healthy control group to identify shared molecular signatures. Our analysis showed that IBD shared the most differential signatures with rheumatoid arthritis, indicating common pathways in their pathogenesis. Psoriatic diseases also shared a significant proportion of differentially expressed and methylated patterns, while SLE had the least in common with other CIDs, suggesting distinct molecular pathways driving its pathogenesis. Interestingly, we were able to identify core transcriptomic changes that persisted even during inactive disease by separating the analysis by disease activity. These signatures were shared across different CIDs and were correlated with DNA methylation changes, reflecting the molecular mechanism of chronicity. Commonly upregulated genes across all CIDs were enriched in pathways related to inflammatory response, cytokine signaling, neutrophil chemotaxis, and humoral immune response. Disease-specific pathways included interferon-beta production in SLE, several metabolic processes in psoriasis, and complement activation in ulcerative colitis. Disease-specific methylation signatures were mainly located in CpG islands, while methylation signatures in enhancers were shared among most diseases. Our large cohort design enabled us to identify subgroup of patients across CIDs that share molecular characteristics, including a cluster of genes related to interleukin and interferon signaling upregulated in 71 samples belonging to different CIDs.

Conclusion

In conclusion, our study identified common and disease-specific molecular signatures in CIDs. Our findings suggest shared immune dysregulation pathways underlying the pathogenesis of IBD and rheumatoid arthritis, as well as potential commonalities between psoriatic diseases. We show the clear presence of core signatures of disease regardless of disease activity, which could represent insights into actionable targets for causative treatments and better disease control of CIDs.

Introduction

According to updated guidelines, non-pedunculated polyps of small size are resected with a cold snare in air dilated intestinal lumen(Conventional Cold Snare Polypectomy-CCSP) [1]. R0 resection rate(R0-RR) using CCSP ranges from 32.9% to 96.6%[2-5] while meta-analyses showed that the incomplete resection rate (IRR) after CCSP was 17.3% [6], highlighting the need for further research regarding the most suitable polypectomy method for small polyps. Recently, several studies have described the benefits of water-aided colonoscopy, as well as safety and efficacy of underwater polypectomy in large colon polyps. However, data on small polyps which are the most commonly diagnosed, are insufficient. In response to this gap in the literature, we conducted the first randomized, double-blind, controlled trial to compare underwater cold snare polypectomy(UCSP) to CCSP for non-pedunculated colon polyps of size 5-10mm.

Aims & Methods

The CCSP procedure involved: opening of the intestinal lumen using air/CO2, snaring of the lesion and surrounding healthy tissue, and excision. On the other, UCSP involved three more steps before snaring of the polyp: complete suction of air, partial opening of the intestinal lumen using sterile water, complete immersion of the lesion in water. In order to determine the IRR, additional biopsies were taken from the horizontal margins of the resection site. All polypectomy–related complications were recorded. The objective of the study was to compare the safety and efficacy between UCSP and CCSP regarding resection of non-pedunculated colon polyps with size 5-10mm. Primary outcome was the investigation of the difference in the rate of area containing muscularis mucosa between the two polypectomy techniques. The secondary outcomes focused on differences in R0-RR, IRR, en-bloc resection, and complications. Patients were allocated with a 1:1 ration to UCSP or CCSP group.If more than one polyp was diagnosed in a patient, then all were resected by the same method. The randomization process was done by using the random numbers method of Microsoft Excel 2016. Both pathologists and patients were blinded.

Results

Between March 2021 and December 2022, a total of 229 patients were enrolled in the study, with 397 polyps(UCSP:198, CCSP:199) included in the per protocol analysis. Results demonstrated that UCSP was superior to CCSP in terms of both muscularis mucosa resection rate (81.72% vs. 72.33%, p=0.003) and IRR (8.5% vs. 3.5%, p=0.05). However, the R0-RR did not differ significantly between the two groups (UCSP: 93.9%, CCSP: 90%, p=0.29). UCSP also achieved a higher rate of en bloc resections than CCSP(98% vs 93.5%, p=0.04). The only complication observed was non-severe intraprocedural bleeding, which was successfully managed during endoscopy(UCSP 0.5%, CCSP 2%, p=0.37). Expert endoscopists in CCSP achieved a higher R0-RR than non-experts (93% vs. 84%, p=0.05), whereas no significant difference in R0 resection rate was observed among different levels of expertise in UCSP. Polyp histology and size were found to affect R0 resection rates in both groups, with serrated histology and sizes of 8-10mm linked to lower R0 resection rates.

Conclusion

UCSP is a safe technique that achieves better results in the resection of muscularis mucosa and is associated with a lower IRR than CCSP, thus reducing the risk of residual or recurrent lesions. Furthermore, the efficacy of UCSP does not depend on the endoscopist's expertise and thus could be the optimal approach for young or inexperienced gastroenterologists.

References

1. Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2017;49:270–97.
2 Maruoka D, Arai M, Akizue N, Ishikawa K, Kasamatsu S, Taida T, Ishigami H, Okimoto K, Saito K, Matsumura T, Nakagawa T, Katsuno T, Kato N. Residual adenoma after cold snare polypectomy for small colorectal adenomas: a prospective clinical study. Endoscopy. 2018 Jul;50(7):693-700. doi: 10.1055/s-0043-124869. Epub 2018 Feb 7. PMID: 29415287. 3
3. Zhang Q, Gao P, Han B, et al. Polypectomy for complete endoscopic resection of small colorectal polyps. GastrointestEndosc 2018;87:733–40
4. Kawamura T, Takeuchi Y, Asai S, et al. A comparison of the resection rate for coldand hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study). Gut 2018;67:1950–7.
5. Papastergiou V, Paraskeva KD, Fragaki M, et al. Cold versus hot endoscopic mucosal resection for nonpedunculated colorectal polyps sized 6-10 mm: a randomized trial. Endoscopy 2018;50:403–11.
6. Djinbachian R, Iratni R, Durand M, Marques P, von Renteln D. Rates of Incomplete Resection of 1- to 20-mm Colorectal Polyps: A Systematic Review and Meta-Analysis. Gastroenterology. 2020;159(3):904-914.e12. doi:10.1053/j.gastro.2020.05.018

Introduction

Several changes in microbes of the gut and decreased diversity especially in inflammatory bowel disease (IBD) are well-known. The exact pathophysiological connection is lacking, but the systemic inflammation due to the microbial alterations are assumed.

Aims & Methods

This study aimed to perform analysis of faecal microbiota composition simultaneously with body composition and lipid characteristics in Crohn’s disease (CD) patients to find specific microbiota profiles connected to altered metabolism and obesity. In our prospective cohort study, CD patients were enrolled. At the inclusion, demographic and clinical data, blood, and faecal samples were obtained. Disease activity was assessed by CDAI, and SES-CD. Laboratory tests were made including C-reactive protein (CRP), albumin and lipids (triglyceride, cholesterol). Faecal bacterial composition was assessed using shotgun method. Each patient underwent a body composition analysis via bioelectrical impedance analysis. A nutritional questionnaire was filled by each subject.

Results

We analysed 27 CD patients in this study (median age was 35 IQR 13.5 years). A 44,4% and 27,3% of patients were obese based on BMI and VFA. Beta diversities were higher in non-obese patients (VTA, p<0,001), however relative abundances did not differ. Firmicutes has a lower, while C.innocuum has a higher abundance at high cholesterol level (p=0,001, p=0,0034). Adlercreutzia, B.longum and Blautia alterations were correlated with triglyceride level. Higher Clostridia (p=0,009) and B.schinkii (p=0,032) and lower Lactobacillus (p=0,035) were connected to high VFA. B.bifidum had richness amongst low-weight patients (p=0,01). Beside Clostridia, Eubacteriales and R.hominis also correlated with waist-hip ratio (p=0,04, p=0,04 and p=0.048). Higher body fat mass was paired with increased B.schinkii (p=0,021) and decreased L.paragasseri (p=0,015) and R.intestinalis (p=0,035). Disease activity was coupled with dysbiotic elements. Microbiota alterations were found during different treatments.

Table 1. Baseline demographic and clinical characteristics of the study population [n = 27]

	n = 27
Gender (male, N, %)	9 (33.3)
Age (years, median (IQR)	35 (13.5)
Disease duration (years, median (IQR)	7 (11.0)
CDAI at inclusion, mean (± SD)	141 (97.2)
SES-CD at inclusion, mean (± SD)	7.4 (8.0)
Fecal calprotectin (ug/g, median, (IQR))	728.6 (626.3)
CRP at inclusion, mean (± SD)	17.0 (35.3)
Serum cholesterol (mmol/l, mean, ± SD)	4.3 (0.9)
Serum triglyceride (mmol/l, mean, ± SD)	1.6 (1.0)

Conclusion

Changes in Blautia, Lactobacillus, Clostridia and Bifidobacterium abundances in obesity highlight the importance of gut microbiota in diseases with similar inflammatory background. It suggests to treat obesity to achive better disease contol in IBD and it helps to develop new therapeutic approaches, such as pre- or probiotics or personalized faecal microbiota transplantation.

Introduction

While patients with Sickle Cell Disease (SCD) often exhibit digestive manifestations, the underlying pathophysiology remains poorly understood. SCD could notably affect the intestinal mucosa through microvascular phenomena. Co-occurrence of SCD and Inflammatory Bowel Diseases (IBD) has been reported in a very limited number of cases.
Our aim was to explore the intersection between SCD and IBD, particularly focusing on the impact of SCD on the natural course of IBD and the safety profile of drugs in this high-risk population.

Aims & Methods

We conducted a multicenter retrospective case-control study involving all adult patients diagnosed with both IBD and concomitant SCD and followed in 3 tertiary university hospitals. Each IBD patient with SCD was matched with up to 4 IBD patients without SCD, based on disease phenotype (UC or CD), sex, date of birth (±3 years), length of disease follow-up (±2 years), and year of diagnosis (±3 years). The primary outcome was a complicated disease course, defined by a composite outcome including intestinal resection, perianal surgery, and/or the need for advanced therapy.

Results

Overall, 125 patients with IBD were studied, including 24 with concomitant SCD and 101 controls. Of the 24 SCD patients, 5 (20.8%) had Crohn's disease (CD), 17 (70.8%) had ulcerative colitis (UC) and 2 (8.3%) had indeterminate colitis. 23/24 (95 %) had colonic involvement. Of note, 8 of 24 (33.3%) SCD patients had concomitant primary sclerosing cholangitis (PSC) compared to 1% of patients in the control group (p<0.001). Survival without a complicated course of the disease was estimated at 58.7 % (IC95[49.6-69.5]) at 5 years and at 38.9% (IC95[29.9-50.4]) at 10 years, for non-SCD patients, and at 63.3% (IC95[45.7-87.6]) and 52.7% (IC95[34.9-79.6]) at 5 and 10 years, respectively, for patients with SCD and IBD (p=0.36, Log-rank test). The survival without the need of advanced therapy was estimated at 66.1% (IC95[57.3-76.2]) at 5 years for non-SCD patient, and at 78.2% (IC95[63-97.2]) in patients with SCD patients (p=0.45).
Regarding the safety profile, 26.3% (5/19) of patients with SCD and 13.5 % (14/104) of controls experienced adverse events with advanced therapies (p=0.17, Fisher’s exact test). There was one reported vaso-occlusive crisis associated with the use of thiopurines. No death occurred during follow-up.

Conclusion

While patients with SCD and IBD displayed a distinctive phenotype characterized by nearly constant colonic involvement and a high prevalence of associated PSC, the disease natural history of IBD did not differ from that of patients without SCD. Given the notable prevalence of PSC, systematic screening with cholangio-MRI should be considered. Furthermore, no significant safety signal regarding the use of immunomodulator or advanced therapy was raised.