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Introduction

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by corpus oxyntic mucosa atrophy and impaired gastric acid secretion(1,2). The increased gastric cancer (GC) risk in AAG is still debated. One mechanism favoring gastric carcinogenesis may be increased intragastric pH leading to intragastric microenvironment changes and facilitating bacterial dysbiosis(3-5). Oral microbiota and periodontal-dental disorders alterations have been linked to increased GC risk as well(6-8). In AAG, the increased intragastric pH may lead to survival of swallowed bacteria, possibly further contributing to the increased GC risk. The oral and gastric microbiota composition together have not been investigated so far in AAG patients.

Aims & Methods

The aim of the study was to investigate the oral and gastric microbiota composition in AAGpts in order to clarify the role of oral bacteria in gastric dysbiosis.
We conducted a case-control study: n=20 histologically diagnosed AAGpts(F75%,age 64 yrs) and n=20 ctrs with healthy stomach(HS)(F45%,age 56 yrs). From all pts and ctrs a sputum sample was obtained in the morning fasting without tooth brushing. Within 1 hour after sputum collection, pts and ctrs underwent gastroscopy with biopsies (updated Sydney system) for histopathological assessment and one further corpus biopsy for DNA extraction. Sputum(n=40) and biopsy(n=40) samples were collected in vials with DNA shield and frozen at -20°C since processing. DNA was extracted (QIAmp DNA kit) and prepared (Illumina Nextera XT DNA Library Preparation Kit). Paired-end sequencing was performed (Illumina MiSeq sequencer,MiSeq Reagent Kit v3). Fastq files were filtered to remove low-quality reads; filtered reads were taxonomically classified and subjected to Homo sapiens filtering (METAnnotatorX2 pipeline, up-to-date RefSeq database, NCBI).

Results

AAGpts and ctrs were similar with regard to clinical features, oral hygiene and paraodontal-dental disorders. Bacterial abundance in biopsies was higher in AAGpts than in ctrs (403 vs 223,p=0.06), but not different in sputum (27,728 vs 31,544,p=0.54). On biopsies, AAGpts showed a lower Shannon Index than ctrs (2.553 vs 2.617, p=0.001). On sputum, AAGpts showed a higher Shannon Index than ctrs (2.828 vs 2.738, p=0.0). Beta-diversity (Bray-Curtis dissimilarity) was not different between pts and ctrs, neither in sputum nor biopsies.
At the taxa level, in biopsies Streptococcus oralis, Fusobacterium pseudoperiodonticum, Veillonella rogosae, and Gemella sanguinis were significantly associated with pts(p<0.03); while in sputum the most significant associations were G.sanguinis, Prevotella multisaccharivorax, F.nucleatum, and F.peridonticum(p<0.03). The most abundantly shared taxa between sputum and biopsy were S.oralis and P.histicola, while G.sanguinis, F.pseudoperidonticum, and V.rogosae were shared in pts only.

Conclusion

This study confirmed gastric dysbiosis in AAG as shown by lower biodiversity and evenness. Gastric bacterial abundance was higher in AAG, probably due to non-acidic gastric pH permitting overgrowth of gastric bacteria. Oral bacterial abundance was similar in AAG and ctr with higher biodiversity-evenness in AAG pts, probably due to upstream passage of unactivated bacteria from stomach to mouth. Oral taxa related to increased GC risk were more commonly associated to AAG and shared between mouth and stomach. In AAG these findings show the role of oral microbiota in gastric dysbiosis, possibly contributing to increased GC risk.

References

1) Lenti MV,Rugge M,Lahner E,Miceli E,Toh BH,Genta RM,De Block C,Hershko C,Di Sabatino A. “Autoimmune gastritis” Nat Rev Dis Primers. 2020 Jul 9;6(1):56.
2) Rugge M,Genta RM,Malfertheiner P,Dinis-Ribeiro M,El-Serag H,Graham DY,Kuipers EJ,Leung WK,Park JY,Rokkas T,Schulz C,El-Omar EM;RE.GA.IN;the Real-world Gastritis Initiative-updating the updates. Gut. 2024 Feb 23;73(3):407-441. doi: 10.1136/gutjnl-2023-331164. PMID: 38383142.
3) Conti L, Annibale B, Lahner E. Autoimmune Gastritis and Gastric Microbiota. Microorganisms. 2020;8(11):1827. Published 2020 Nov 19. doi:10.3390/microorganisms8111827
4) Lin L, Li W, Yan L, et al. Comparison of gastric microbiota in patients with different gastric lesions in high and low risk areas of gastric cancer. BMC Microbiol. 2025;25(1):202. Published 2025 Apr 9. doi:10.1186/s12866-025-03926-4
5) Conti L, Borro M, Milani C, et al. Gastric microbiota composition in patients with corpus atrophic gastritis. Dig Liver Dis. 2021;53(12):1580-1587. doi:10.1016/j.dld.2021.05.005
6) Huang C, Li Y, He C. Oral microbes and gastrointestinal cancers: new strategies and insights. Clin Transl Oncol. Published online April 5, 2025. doi:10.1007/s12094-025-03891-4
7) Xia R, Jiang Z, Zhou Y, et al. Oral microbiota and gastric cancer: recent highlights and knowledge gaps. J Oral Microbiol. 2024;16(1):2391640. Published 2024 Aug 16. doi:10.1080/20002297.2024.2391640
8) Aguiar FJN, Menezes FDS, Fagundes MA, et al. Gastric adenocarcinoma and periodontal disease: A systematic review and meta-analysis. Clinics (Sao Paulo). 2024;79:100321. Published 2024 Jan 31. doi:10.1016/j.clinsp.2023.100321

ORAL AND GASTRIC MICROBIOTA COMPOSITION IN PATIENTS WITH AUTOIMMUNE ATROPHIC GASTRITIS

Sophia Cingolani 1, Laura Belloni 1, Federico Fontana 2, Giulia Stendardo 1, Francesca Fabretti 1, Marica Vavallo 1, Giulia Pivetta 1, Emanuele Dilaghi 1, Marco Ventura 2, Gianluca Esposito 1, Bruno Annibale 1, Christian Milani 2, Edith Lahner 1

1 Sapienza University of Rome, Roma, Italy

2 University of Parma, Parma, Italy

Conference

UEG Week Berlin 2025

Topics

Oesophagus

Submission format

Abstract

Session

OESOPHAGEAL, GASTRIC AND DUODENAL (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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Advancing IBD precision medicine: The next frontier

Bram Verstockt 1

1 University Hospitals Leuven and KU Leuven, Translational Research in Gastrointestinal Disorders - IB, Leuven, Belgium

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine

Session

The art of making clinical research precise: Predicting therapy response in IBD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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Medical treatment

David Surendran Sanders 1

1 Royal Hallamshire Hospital - NHS Trust, Royal Hallamshire Hospital; Sheffield/GB, Sheffield, United Kingdom

Event

UEG Week Berlin 2025

Topics

Immunology Small Intestine & Nutrition

Session

Coeliac or non-coeliac enteropathy?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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TREATMENT OF CROHN'S COMPLEX PERIANAL FISTULAS WITH MICRO-FRAGMENTED AUTOLOGOUS ADIPOSE TISSUE INJECTION: AN ITALIAN MULTICENTER RANDOMIZED CONTROLLED TRIAL (ATTIC)

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Introduction

Complex perianal fistulas represent one of the most challenging manifestations of Crohn’s disease. Combined surgical and medical therapy with biologic drugs represents today the first-line treatment option, but its efficacy does not exceed 60% in terms of healing. Recently, new therapeutic approaches, such as autologous microfragmented adipose tissue (M-Fat) injection, have shown promising results. Indeed, a recent non-profit prospective pilot study on 15 patients has demonstrated that the local injection of M-Fat is a safe and promising “rescue therapy” for patients with multiresistant complex fistulizing Crohn’s disease (PCD), with a 66.7% rate of combined remission in such difficult patients. It has to be highlighted that the M-Fat injection is minimally invasive, with less risk of sphincteric damage and can be carried out in day-surgery setting.

Aims & Methods

The primary aim of this multicentre double-blind randomized controlled trial (ATTIC) is to evaluate the efficacy of the infiltration of M-Fat in the healing of perianal complex fistulas not-responding to treatment with biologics. Consecutive patients referring to the 6 investigation Centers for surgical treatment of persistent complex fistulizing PCD refractory to biosurgical approach were assessed for eligibility. After baseline pelvic magnetic resonance imaging, those included were submitted to surgical drainage with “cone-like” fistulectomy, and then randomized to receive a 15 to 20 cc local injection, at the internal orifice level and along fistula tracts, of M-Fat obtained by a lipoaspiration and processed with an enzyme-free technology (treatment group), or a suture placement and injection of 15 cc of saline solution at the internal orifice (control group). Clinical follow-up were conducted at 2, 4, 8, 12, and 24 weeks; at 24 weeks after surgery, pelvic magnetic resonance was obtained. Success was defined as “combined remission”, combination of clinical (absence of drainage upon gentle finger compression) and radiological healing (absence of residual collections > 3 mm). Clinical remission was defined as clinical healing of all external openings not confirmed at radiological assessment.

Results

An overall 92 patients were screened, and 66 (33 per group) completed the 24-week follow-up. A statistically significant difference in favour of the treatment group in terms of combined remission emerged at the primary endpoint at 24-week follow-up (control group, 18.18%; treatment group: 57.58%; p = 0.0020). No significant differences in clinical outcome measures were encountered at any of the other follow-up points. No significant differences emerged between the groups in terms of recurrence rate, complication rate, and number of adverse events. Clinical remission was 63.64% in the treatment group compared to 51.52% in the control group with no statistically significant difference (p > 0.05).

Conclusion

This multicentre double-blind randomized controlled trial demonstrates that the intraoperative injection of M-Fat, associated with surgical complete drainage of perianal sepsis, is safe, effective, and reproducible in healing complex multirefractory perianal Crohn's disease, while improving the quality of life and significantly reducing the risk of definitive oostomy.