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.
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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
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Introduction

Patients with ulcerative colitis (UC) are at an increased risk of cytomegalovirus (CMV) infection. CMV infection in acute severe ulcerative colitis (ASUC) may worsen disease severity and clinical outcomes. Current guidelines recommend colonic biopsies for the exclusion of CMV in all patients with ASUC. One study found that CMV positivity in ASUC was associated with greater need for rescue therapy, longer hospital length of stay (LOS) and higher readmission rates but found no difference in rate of colectomy.¹ We aimed to investigate the impact of positive CMV result on clinical outcomes in patients presenting with ASUC.

Aims & Methods

A retrospective review included all ASUC presentations to a quaternary hospital over a 10-year period based on modified Truelove and Witts’ criteria. ASUC presentations were grouped based on CMV positivity as determined by colonic biopsy. Data on pre-admission medications was collected. Data was collected on rates of rescue therapy, referral to colorectal surgery, colectomy, total parenteral nutrition (TPN). Outcomes assessed included intensive care unit (ICU) admission, 30- and 90-day readmission rates, 30- and 90-day mortality rates and mean LOS.

Results

A total of 172 ASUC presentations were identified. Of these, 133 had available colonic biopsy CMV results. 11 patients (8%) had positive CMV. Positive CMV result was significantly associated with increased need for TPN (36% vs 11%, p=0.02), ICU admission (27% vs 5%, p=0.004) and referral to colorectal surgery (82% vs 43%, p=0.01). Patients with CMV had longer LOS (27.1±14.0 vs 11.0±7.4, p=0.003). There were no significant differences in rates of rescue therapy, inpatient colectomy, readmission or mortality rates. 9 of the patients (82%) were treated with ganciclovir or valganciclovir. Patients on maintenance advanced UC therapies, including biologics and small molecule inhibitors, had significantly higher rate of CMV (22% vs 5%, p=0.01). Biologic therapy alone was associated with higher rate of CMV (24% vs 7%, p=0.02), whereas small molecule inhibitor alone was not (p=0.6). Pre-admission use of 5-aminosalicylates, high dose steroids, thiopurines or combination therapies were not associated with CMV positivity.

Table 1: Comparison data of clinical outcomes in ASUC between patients with and without CMV positivity on colonic biopsy

Conclusion

Patients with CMV positive colonic biopsies tend to require more inpatient interventions, including increased need for TPN, ICU admission, referral to colorectal surgery and longer hospital length of stay. Despite more complex admission course of ASUC patients with concurrent CMV infection, these patients were not observed to have worse outcomes than those without CMV diagnosis. Maintenance biologic and small molecule inhibitor use was associated with higher rates of CMV, reflecting the immunosuppressant effects of advanced UC therapies. CMV detection needs to be considered as a potential exacerbating factor in disease severity.

References

1. Huang D, Rennie M, Krasovec A, Nagubandi S, Liu S, Ge E, Khehra B, Au M, Sivagnanam S, Kwan V, Rogge C, Mitrev N, Kariyawasam V. Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study. Ther Adv Chronic Dis. 2024 Mar 28;15:20406223241233203. doi: 10.1177/20406223241233203. PMID: 38560721; PMCID: PMC10981253.

Introduction

Vedolizumab (VDZ), a monoclonal antibody therapy approved for moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) in China in 2020¹ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.² However, there is limited data on VDZ's real-world effectiveness and safety in Chinese IBD patients.³ Interim results from the VALUE study that enrolled patients with UC have been published ^3,4 and final results are reported here.

Aims & Methods

VALUE (NCT04872491), a multicenter, single-arm, prospective, observational study evaluated the safety and effectiveness of VDZ in adult Chinese patients with IBD (N = 500) over 72 weeks. Clinical response, clinical remission, and endoscopic remission were assessed at Weeks 14, 30, and 54. Partial Mayo and Mayo endoscopic subscores at baseline and Weeks 14, 30, and 54 were calculated. Clinical response was defined as ≥2-point reduction in Partial Mayo Clinic score and ≥25% decrease from baseline score accompanied with ≥1-point decrease in the rectal bleeding or absolute rectal bleeding subscore ≤1. Clinical remission was defined as Partial Mayo Clinic score ≤2 with no subscore >1, endoscopic remission as Mayo endoscopic subscore ≤1, and complete endoscopic remission as Mayo endoscopic subscore 0. Safety results and CD patients’ data are presented in separate VALUE abstracts (IDs: AS-UEG-2025-01329 and AS-UEG-2025-01324).

Results

Among 409 UC patients enrolled in the final analysis, 91.9% (376/409) were included in the effectiveness analysis set. Mean age (±standard deviation [SD]) of patients was 46.3 (±15.1) years, and 59.4% (n=243) were male. At baseline, 30.8% (126/409) of patients had moderate UC, and 29.8% (122/409) had severe UC. The median duration of UC was 2.5 years, concomitant steroids were prescribed in 18.9% (71/376). Mean (±SD) partial Mayo score was 5.1 (2.1) at baseline, which declined to 1.7 (1.7), 1.5 (1.7) and 1.3 (1.5) by Weeks 14, 30 and 54, respectively, post-VDZ treatment. Patients achieving clinical response, clinical remission, endoscopic remission, and complete endoscopic remission were 76.9% (220/286), 71.1% (207/291), 63.6% (35/55), and 21.8% (12/55) at Week 14; 78.1% (193/247), 76.3% (190/249), 63.6% (28/44), and 27.3% (12/44) at Week 30; and 80.3% (155/193), 83.3% (165/198), 71.4% (20/28), and 50.0% (14/28) at Week 54, respectively. Patients with moderate and severe UC; biologic naïve patients and patients with prior exposure to biologics at baseline also achieved clinical response, clinical remission, and endoscopic remission (Table). Compared with baseline, mean (±SD) reduction of C-reactive protein (mg/L) at Weeks 14, 30, and 54 were 7.8 (20.2), 6.5 (22.2), and 3.4 (24.8), respectively; mean (±SD) reduction of fecal calprotectin (mu g/g) was 42.7 (150.7) at Week 14 and 212.6 (480.1) at Week 30. The proportion of patients achieving clinical remission without steroid use by Week 14 was 37.7% (23/61), which increased to 60.6% (20/33) by Week 54.

Conclusion

This study indicated that VDZ demonstrated a good effectiveness profile in Chinese UC patients in the real-world setting.

References

1. Yan J et al., Medicine (Baltimore). 2024; 103: e38759.
2. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
3. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.
4. Yan C et al. Am J Gastroenterol. 2023; 119: S894-S895.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Xiuli Zuo, Ye Chen, and Yingchao Li have no conflicts of interest. Lifei Gu and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.