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EFFICACY AND SAFETY OF FECAL MICROBIOTA TRANSPLANTATION FOR THE TREATMENT OF SEVERE AND SEVERE-COMPLICATED CLOSTRIDIOIDES DIFFICILE INFECTION: REPORT FROM A LARGE-VOLUME FMT CENTER

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Introduction

Clostridioides difficile infection (CDI) includes severe clinical pictures of disease that are associated with considerable risk of complications, including bloodstream infection, toxic megacolon, death, and others, and represent a relevant burden for healthcare system.1,2 Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI,3 but its role in severe clinical pictures of CDI is still not well defined.

Aims & Methods

Our aim is to report efficacy and safety of FMT in a large cohort of patients with severe and severe-complicated CDI.
We included consecutive patients with severe CDI treated with FMT at our center from June 2013 to January 2023. Severe and severe-complicated CDI were defined according to international guidelines.1,2 We collected demographical and baseline clinical data of patients, including age, sex, risk factors for CDI, comorbidities assessed with the Charlson Comorbidity Index (CCI), number of previous CDI recurrences. Enrolled patients were followed up with visits or telephone calls up to 12 weeks after the last FMT.
The primary outcome was the clinical resolution of CDI (defined as resolution of diarrhea) at 8 weeks after FMT, while the secondary outcomes were the overall survival at 90 days, and the safety of FMT. Candidate stool donors were screened, following international guidelines (3-5), through a preliminary interview, blood tests, stool tests, and, more recently, with nasopharyngeal swab for SARS-CoV-2.
FMT procedures were carried out by colonoscopy, after a 3-day pre-treatment with oral vancomycin and bowel cleansing, using a single-donor solution of at least 50 grams of fresh feces (before 2017) or frozen feces (after 2017). All patients received at least one fecal infusion. Moreover, after 2015 we planned a sequential FMT approach in this subset of patients, by repeating FMT until the disappearance of diarrhea.

Results

In the study period, 85 patients were enrolled. Of them, 71 had severe CDI and 14 had severe-complicated CDI. Of them, 54 (63,5%) were female, and the mean age was 73 years while the median number of CDI recurrences was 2.
Overall, 39 patients had history of chronic therapy with PPIs, 68 patients had history of antibiotic therapy in the 30 days prior to FMT, 72 patients were hospitalized, and 24 patients were bedridden. The mean CCI was 5.5.
Forty-four patients received sequential FMT, for a total of 158 FMT procedures. Most procedures were performed using frozen feces (n= 102, 64.6%) from unrelated donors (n= 137, 86.7%).
Overall, 76 patients (89.4%) experienced resolution of CDI (65 with severe CDI and 11 with severe-complicated CDI). Thirty-six patients (47.4%) achieved CDI cure with a single FMT procedure.
Fifteen patients (17.6%) died within the 12-week follow-up period. Seven of the 15 patients died for overwhelming CDI. No deaths were attributable to FMT.
At multiple linear regression, enticement was significantly associated with lower CDI cure (p= 0.0026) and higher risk of death (p= 0.0013).
We observed also severe adverse events in 4 patients (4.7%). Three patients developed a bloodstream infection and one patient with chronic heart failure experienced an episode of acute heart failure after FMT. All these events were transient and resolved in few days.

Conclusion

In a large cohort of patients from a high-volume FMT center, FMT was a highly effective and safe treatment for severe and severe-complicated CDI, being also associated with high rates of overall survival in the mid-term. Enticement was identified as a risk factor for FMT failure and death.

References

1) PMID: 34678515
2) PMID: 24118601
3) PMID: 28087657
4) PMID: 32620549
5) PMID: 31563878

EFFICACY AND SAFETY OF FECAL MICROBIOTA TRANSPLANTATION FOR THE TREATMENT OF SEVERE AND SEVERE-COMPLICATED CLOSTRIDIOIDES DIFFICILE INFECTION: REPORT FROM A LARGE-VOLUME FMT CENTER

Gianluca Ianiro 1, Luca Masucci 2, Simone Varca 2, Andrea Severino 2, Marcello Fiorani 2, Serena Porcari 2, Stefano Bibbò 2, Gianluca Quaranta 2, Debora Rondinella 3, Federica Pelliccia 3, Gabriele Altieri 3, Stefano Ruggiero 3, William Fusco 2, Tommaso Rozera 2, Federica Iannarelli 2, Maurizio Sanguinetti 4, Antonio Gasbarrini 5, Giovanni Cammarota 6

1 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome, Rome, Italy

2 Fondazione Policlinico Gemelli, Roma, Italy

3 Università Cattolica del Sacro Cuore, Roma, Italy

4 Catholic University of Rome, Roma, Italy

5 Fondazione Policlinico Universitario Gemelli IRCCS, Università’ Cattolica, Rome, Italy

6 Catholic Univerisity, Fondazione Policlinico Gemelli, Rome, Italy

Event

UEG Week Copenhagen 2023

Topics

Colorectal Digestive Oncology Gut Microbiota IBD Pancreas

Submission format

Abstract

Session

Gut microbiome: From bench to bedside

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Presentation

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Summary: Disease activity in IBD - When and how hard to look for it?

Fernando Magro 1

1 Centro Hospitalar São João, Amadora, Portugal

Event

UEG Postgraduate Teaching Programme 2023

Topics

Education & Training IBD

Session

Disease activity in IBD: When and how hard to look for it?

Published

2023

UEG Presentation

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DISRUPTION OF TUFT CELL–ILC2 IMMUNE HOMEOSTASIS BY THE NANOPLASTICS–GUT MICROBIOTA–SUCCINATE AXIS EXACERBATES ILEAL INFLAMMATION

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Introduction

Inflammatory bowel disease (IBD) is a growing global health concern, especially in industrializing nations where westernized lifestyles drive rising incidence. Its etiology involves genetic, immune, and environmental factors. ^[1]. Plastics are extensively used in industry and daily life, and global plastic production is projected to exceed 34 billion tonnes by 2050^[2]. After release into the environment, plastic waste degrade into micro- (0.1 µm–5 mm) and nanoplastics (<0.1 µm)^[3]. These emerging pollutants are persistent, bioaccumulative, and the gastrointestinal tract is the primary interface for NPs exposure. The gut is the primary exposure route: adults ingest 0.1–5 g/week of micro-/nanoplastics^[4]. Fecal microplastic levels correlate with IBD severity^[5]; animal studies show these particles disrupt microbiota, alter short-chain fatty acids, impair the barrier, and trigger inflammation^[6]. However, most existing research is limited to histopathological observations; the cellular and molecular mechanisms underlying NP toxicity in the small intestine remain poorly understood, hindering systematic risk assessment and development of IBD prevention strategies.

Aims & Methods

To elucidate the dynamics of NP distribution and toxicity, we established a fluorescent-tracking system and reared mice in a plastic-free environment. Mice were orally exposed to 100 nm polystyrene nanospheres for or 3 or 6 weeks. We used fluorescent imaging, histology (H&E, PAS), immunofluorescence, electron microscopy, targeted metabolomics, and 16S rRNA sequencing to assess toxicity across small-intestinal regions. We tested succinate supplementation and compared effects in germ-free mice and small-intestinal organoids to distinguish microbiota-dependent from direct epithelial toxicity.

Results

Fluorescent imaging provided in vivo evidence for an enterohepatic–gallbladder circulation of NPs: following intestinal absorption, NPs first accumulate in the liver, are secreted into the gallbladder with bile acids, become concentrated between meals, and are released back into the gut upon gallbladder contraction after feeding. Prolonged NPs exposure induced chronic inflammatory cell infiltration in the small intestine, with significant reductions in crypt density, Tuft cell, goblet cell, and Paneth cell numbers, accompanied by neutrophil infiltration and decreased group 2 innate lymphoid cells (ILC2s). These changes were most pronounced in the ileum. NPs exposure also significantly reduced succinate levels in cecal contents—without altering tissue succinate—and markedly decreased the relative abundance of succinate-producing bacterial taxa. Succinate supplementation effectively reversed all of these alterations. Under germ-free conditions, NP-induced toxicity was abolished, and no direct toxic effect on Tuft cells was observed in intestinal organoids.

Conclusion

Oral NP exposure undergoes enterohepatic–gallbladder recirculation, resulting in sustained high NPs concentrations in the intestinal mucosa. The ileum is the most susceptible region, and NP toxicity depends on the gut microbiota: NP-induced dysbiosis impairs luminal succinate production, leading to depletion of ileal Tuft cells, which in turn diminishes proliferation and activation of goblet cells, Paneth cells, and ILC2s. Succinate supplementation rescues NP-induced ileal immune dysfunction. While plastic products have provided immense convenience, their uncontrolled use may contribute to the rising incidence of IBD. Our study delineates the mechanism by which NPs exacerbate ileal inflammation and proposes a feasible intervention strategy.

References

1. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Lancet. 2017;390(10114):2769-78.
2. Luo D, Chu X, Wu Y, Wang Z, Liao Z, Ji X, et al. J Hazard Mater. 2024;465:133412.
3. Kumar M, Chen H, Sarsaiya S, Qin S, Liu H, Awasthi MK, et al. J Hazard Mater. 2021;409:124967.
4. Senathirajah K, Attwood S, Bhagwat G, Carbery M, Wilson S, Palanisami T. J Hazard Mater. 2021;404(Pt B):124004.
5. Yan Z, Liu Y, Zhang T, Zhang F, Ren H, Zhang Y. Environ Sci Technol. 2022;56(1):414-21.
6. Zhang Z, Xu M, Wang L, Gu W, Li X, Han Z, et al. Environ Int. 2023;182:108353.

DISRUPTION OF TUFT CELL–ILC2 IMMUNE HOMEOSTASIS BY THE NANOPLASTICS–GUT MICROBIOTA–SUCCINATE AXIS EXACERBATES ILEAL INFLAMMATION

wentao shao 1, Yulong Yang 2, Anhua Huang 2, Zhaoyan Jiang 2, Aihua Gu 3

1 Nanjing Medical University, Nanjing, China|||Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China, Shanghai, China|||Southeast University, Nanjing, China

2 Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China, Shanghai, China

3 Nanjing Medical University, Nanjing, China|||Nanjing Medical University, Nanjing, China

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine Small Intestine & Nutrition Radiology & Imaging

Submission format

Abstract

Session

IBD: What about the environment?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Gastroparesis in children

Michiel van Wijk 1

1 Emma Childrens Hospital, AMC, Amsterdam, Netherlands

Event

UEG Week Copenhagen 2023

Topics

Endoscopy Standards & Guidelines Stomach & H. Pylori

Session

Therapy update: Gastroparesis

Published

2023

UEG Presentation

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The role of diet in the management of IBD

João Sabino 1

1 Leuven University Hospital, Leuven, Belgium

Event

UEG Week Vienna 2024

Topics

IBD Small Intestine & Nutrition Primary Care

Session

Nutrition in pathogenesis and treatment of lower GI disorders

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Poster

Audio / Video Poster

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Introduction

Inflammatory bowel diseases (IBD) carry a high risk of complications if not diagnosed promptly and are often misdiagnosed as irritable bowel syndrome (IBS). Delayed IBD detection leads to an increase in complicated cases and missed opportunities for timely therapy initiation.

Aims & Methods

The study aimed to develop an AI-based clinical decision support system (CDSS) for IBD diagnosis.
We created three databases, containing clinical-laboratory data, endoscopic and histopathological images. Patients enrolled from 2014 to 2024 included those with confirmed IBD (ulcerative colitis (UC) and Crohn’s disease (CD) with colonic involvement) during flare-ups and IBS with normal endoscopic and histopathological findings.
Separate artificial neural networks were designed for IBD differentiation: multilayer perceptrons (MLPs) for clinical-laboratory data analysis and a pre-trained VGG16 convolutional neural network (CNN) for digital image analysis (initialized with ImageNet weights).
This work has been supported by the grants the Russian Science Foundation, RSF 24-25-20127.

Results

A retrospective database of 1,406 patients with clinical and laboratory data was compiled. For IBD vs. IBS differentiation, the cohort was reduced to 390 patients that had all the fulfilled data, while UC vs. CD analysis included 964 patients.
An MLP (13:13-5-1:1) achieved 92.7% and 99.0% accuracy in IBD diagnosis, incorporating stool frequency/consistency, absence of extraintestinal/perianal manifestations, functional disorders, family history of autoimmune diseases, prior surgeries, CRP, and fecal calprotectin (p≤0.019).
Another MLP (9:9-8-1:1) detected 70.16% of CD and 86.40% of UC cases, using data on constipation, diarrhea, bloody stools, absence of extraintestinal manifestations, fever, perianal lesions, strictures, and prior bowel surgeries (p<0.001).
The endoscopic database comprised 5,693 JPEG images: 3,400 of normal mucosa, 1,357 - CD, 935 - UC. Model sensitivity and specificity were for CD - 91%/79%; UC - 90%/97%; normal - 90%/97%.
The histopathological dataset included 398 whole-slide images (1280×960 px), segmented into 224×224 px tiles. The final set included 8,620 images: 2,360 - CD, 2,320 – normal mucosa, 3,950 - UC. Sensitivity and specificity were for CD - 91% and 95%, UC - 96%, 95%, normal - 96%, 93%, respectively.
The integrated clinical DSS was constructed using Bayesian belief networks implemented in Hugin Lite 8.3 software and integrated clinical, endoscopic, and histopathological nodes. The network architecture replicated the stepwise diagnostic process and incorporated the following nodes: clinical and laboratory data, endoscopy (IBD/IBS differentiation), histopathology (IBD/IBS differentiation), IBS, IBD, endoscopy (UC/CD diagnosis), histopathology (UC/CD discrimination), final diagnosis. The system was validated using six patients per diagnostic category (IBS, UC, CD), with complete sets of clinical, endoscopic, and histopathological data required for all component models. The integrated model demonstrated an overall diagnostic accuracy of 83.3%.

Conclusion

The developed CDSS shows promise for earlier IBD detection but requires further validation studies.

AI-BASED DECISION SUPPORT SYSTEM FOR DIAGNOSING INFLAMMATORY BOWEL DISEASES

Igor Bakulin 1, Irina Rasmagina 1, Gleb Mashevskiy 2, Natalia Sheliakina 1, Grant Arutyunyan 1

1 North-Western State Medical University n.a. I.I.Mechnikov, Saint Petersburg, Russian Federation

2 North-Western State Medical University n.a. I.I.Mechnikov, Saint Petersburg, Russian Federation|||St. Petersburg Electrotechnical University “LETI”, Saint Petersburg, Russian Federation