Introduction

Gut dysbiosis reduces immunogenicity of non-COVID-19 vaccines. While immunogenicity of BNT162b2 wanes with time, factors influencing durability of vaccine immunogenicity are underinvestigated.

Aims & Methods

Aim: We aimed to investigate association between gut microbiota composition and longer-term immunogenicity of BNT162b2.
Methods: This was a prospective cohort study recruiting adult BNT162b2 two-dose recipients from three vaccination centers in Hong Kong. Exclusion criteria included prior COVID-19, gastrointestinal surgery and immunocompromised status. Blood samples were collected at baseline and day180 after first dose, and tested for neutralising antibody (NAb) against receptor-binding domain (RBD) of wild type SARS-CoV-2 virus using chemiluminescence immunoassay. NAb seroconversion (defined as >=15 AU/mL) was determined at day180. Those with NAb 75^th percentile and <75^th percentile were classified as high- and low-responders, respectively. Stool samples were collected at baseline, followed by DNA extraction and shotgun metagenomic sequencing by Illumina NovaSeq 6000 platform. Relative abundances of microbial taxa were compared between high- and low-responders. Alpha-diversity was estimated by observed species, Shannon and Simpson indices, and compared between the two groups using Wilcoxon signed-rank test. Beta-diversity was compared by non-metric multidimensional scaling (NMDS). Linear discriminant analysis (LDA)-Effect Size (LEfSe) was performed to identify stool bacterial species and metabolic functional pathways with LDA score >=2. Multivariable logistic regression adjusting for clinical factors (including age, sex, diabetes mellitus, overweight/obese) was used to derive adjusted odds ratio (aOR) of persistently high vaccine response with bacterial species.

Results

Of 242 BNT162b2 recipients (median age:50.2 years [IQR:42.5-55.6];male:85 [35.1%]), 232 (95.9%) remained seropositive at day180. 61 (25.2%) of vaccine recipients were persistent high-responders (median NAb level:205.4 AU/mL; IQR:164.6-291.3) while 181 (74.8%) were low-responders (median NAb level:40.9 AU/mL; IQR:25.8-66.4). The baseline demographics were comparable between the two groups (all p>0.05). There was no difference in the alpha and beta diversity between the two gropus (all p>0.05). Ruminococcus bicirculans, Parasutterella excrementihominis, and Streptococcus salivarius were more abundant in high- than low-responders (0.9% vs 0.1%, 0.08% vs 0.02%, 0.06% vs 0.04%, respectively), while Bacteroides thetaiotaomicron was less abundant (1.1% vs 2.1%). Consistently, LEfSe showed that R. bicirculans (log₁₀LDA score=3.65), P. excrementihominis (score=2.82), and S. salivarius (score=2.31), were enriched in persistent high-responders, while B. thetaiotaomicron was enriched in low-responders (score= –3.70). On multivariable analysis, bacterial species including R. bicirculans (aOR:1.87;95% CI:1.02-3.51), P. excrementihominis (aOR:2.20;95% CI:1.18-4.18) and S. salivarius (aOR:2.09;95% CI:1.13-3.94), but not clinical factors, were associated with persistent high response. R. bicirculans positively correlated with metabolic pathways enriched in persistent high-responders, including superpathway of L-cysteine biosynthesis (score=2.25) and L-isoleucine biosynthesis I (score =2.16), which are known to benefit immune system.

Conclusion

Potential microbial markers for longer-term BNT162b2 immunogenicity were R. bicirculans, P. excrementihominis, S. salivarius and B. thetaiotaomicron. Quantitative polymerase chain reaction (qPCR) will be performed in a validation cohort.

Disclosure

Supported by the Health and Medical Research Fund, The Government of the HKSAR (ref no: COVID1903010, Project 16)

Introduction

Proton pump inhibitors (PPIs) are extensively prescribed due to the widespread diagnosis of gastro-oesophageal disease (GORD). ^1,2 Overutilisation of PPIs is common, and growing concerns over adverse events, inappropriate prescribing and unnecessary costs ^3,4 are driving exploration into the implementation of holistic management, including deprescription strategies¹.

Aims & Methods

We aimed to quantify healthcare professionals’ (HCPs) preferences on the management of GORD in the UK, and identify attributes perceived as enhancing or detracting from quality of care.
Attributes were derived from qualitative data gathered through 3 focus groups with gastroenterologists, pharmacists and general practitioners (GPs), and interviews with 4 GORD patients.
A discrete-choice experiment (DCE) was developed and administered via online survey (Jan–Apr 2025) to 38 HCPs. Respondents chose between paired hypothetical GORD management scenarios, varying by symptom severity, appointment frequency, treatment approach, information delivery method, and cost. Preferences were modelled using a multinomial conditional logit with effects coding. Marginal rates of substitution (MRS) were calculated to quantify trade-offs.

Results

74% of respondents were pharmacists (n=28) and 26% GPs (n=10). All had managed GORD patients in the past year, and 81% expressed concern over long-term PPI use.
A holistic approach combining PPIs with lifestyle modification was strongly preferred over PPI monotherapy (β=0.4244, p<0.001), representing the most influential driver of care quality. Lifestyle modification alone was also favoured over PPI monotherapy (β=0.1125), though this did not reach statistical significance (p=0.127).
Respondents expressed significant aversion to providing information via pamphlets compared to GP-led counselling (β=–0.1836, p=0.046), while no preference emerged between pharmacist- and GP-led counselling (β=0.0512, p=0.573). Neither appointment burden nor out-of-pocket costs significantly influenced decision-making.
Symptom severity was a notable driver: HCPs selected scenarios involving moderate symptoms over mild (β=0.2353, p=0.005), indicating increased urgency and prioritisation for moderate disease.
Analysis of MRS between attributes suggested that HCPs are willing to accept 4.4 additional appointments to manage moderate symptoms, rather than mild, and nearly 8 additional appointments to deliver combined holistic lifestyle and pharmacological therapy. This highlights a willingness to absorb appointment-related resource demands in favour of more comprehensive, effective care.

Conclusion

Concerns around long-term PPI use support a shift toward active GORD management and PPI deprescribing, with structured follow-up to monitor treatment response.
This interim analysis highlights a clear preference among HCPs for multimodal GORD management, particularly combining lifestyle modification with pharmacological treatment, and reinforces the importance of interactive clinician[BA1] -led patient education, which can promote compliance and improve outcomes. The willingness to accept 4.4 additional appointments reflects the value placed on ongoing monitoring and personalised care. However, this raises the question on the impact this may have on health services, and whether the integration of self-care into multimodal approaches developed with HCPs could be an alternative solution to be investigated. [LH2] These findings highlight the need for a system-wide shift toward guideline-informed, stepped-care models.
A further analysis on patient population preferences is under review.

References

1. Savarino E, Anastasiou F, Labenz J, Hungin APS, Mendive J. Holistic management of symptomatic reflux: rising to the challenge of proton pump inhibitor overuse. Br J Gen Pract. 2022; 72(724):541-544.
2. Hungin APS, Scarpignato C, Keefer L, Corsetti M, Anastasiou F, Muris JWM, Mendive JM, Kahrilas PJ. Review article: rethinking the "ladder" approach to reflux-like symptom management in the era of PPI "resistance" - a multidisciplinary perspective. Aliment Pharmacol Ther. 2022; 55(12):1492-1500.
3. Plehhova K, Wray J, Aluko P, Sutton S, McArdle J, Dawson A, Coyle C, Stevens RM. Prescribing practices for proton pump inhibitors among primary care physicians in England: an evaluation. BJGP Open. 2025.
4. Sosio J, McKee N, [BA1] [LH2] Gold R, Singson A, Boroda K. S579 PPI Stewardship: A Quality Improvement Tool to Improve Long-Term Prescribing Practices. Am J Gastroenterol. 2024; 119(10S): S400.

Disclosure

This study was funded by Reckitt Benckiser Healthcare Ltd.
K. Plehhova, and E. Horvath are employees of Reckitt.

Introduction

Volatile organic compounds (VOC) in stool samples may reflect functional activity of gut microbiome. Previous studies showed that gut flora may influence transient relaxations of lower esophageal sphincter through short-chain fatty acids production and thus - participate in pathogenesis of gastroesophageal reflux disease (GERD). However, the role of VOC in pathogenesis of GERD is poorly studied yet.

Aims & Methods

The aim of this study (FGMF-2025-0003) was to perform correlation analysis between concentrations of VOC in stool samples and GERD-Q score.
We enrolled willing to participate patients referred to perform multichannel 24-h pH-impedance recording (Ohmega, Laborie). According to the Lyon 2.0 criteria patients were allocated to the GERD or the control group. GERD-Q questionnaire was filled in by the participants on the same day as stool samples were collected. Thermo TSQ 8000 triple quadrupole mass-spectrometer (GC/MS) was used for the measurement of VOCs in stool samples were analyzed with. Correlation analysis (Spearman rank R) was performed between values of 80 VOCs in stool samples and the results of GERD-Q questionnaire.

Results

Data of 76 patients were eligible: 42 with GERD and 34 - of the control group. Participants in the GERD group were older (54.7±12.2 y.o. vs 46±14.9 y.o., P<0.05) and their BMI was greater (30.9±5.2 vs 27.2±6.5 kg/m², P<0.05). GERD-Q score was logically greater in GERD group (11.0±2.5 vs 5.2±1.2, p<0.01). Correlation analysis revealed significant correlations between GERD-Q score and concentrations of 2-methylbutyric acid (Spearman R =-0.31), caproic acid (0.34) and enantiic acid (0.396) in stool samples.

Conclusion

GERD-Q score positively correlates with concentrations of Caproic acid (0.34) and Enantiic acid (0.396) in stool samples and negatively – with 2-Methylbutyric acid. The data of this pilot study may serve as a basis for further research on the role of functional activity of gut microbiome in pathogenesis of GERD.

Introduction

Appropriate knowledge of surface features of colorectal polyps is necessary for their adequate management. Data are limited regarding the diagnostic value of surface pattern-based prediction of histology.

Aims & Methods

This nationwide observational cohort study aimed to compare the optical diagnosis based on Kudo’s pit pattern and the histologic result in case of colorectal polyps endoscopically removed during screening colonoscopies.
Data regarding Kudo’s pit pattern of the lesions (Kudo I-V), and the final histological results were obtained from clinical records of screening colonoscopies which were prospectively collected in the registry of Hungarian National Public Health Institute. The level of agreement was characterized by Cohen’s kappa coefficient. The feasibility of optical diagnostics to differentiate neoplastic and non-neoplastic lesions, as well as to identify submucosally invasive cancer (SMIC) were investigated. The potential effects of polyp size and location (left/right colon), and that of timing of colonoscopy (1st period between 2019 and 2021, and 2nd period between 2022 and 2023) were also evaluated.

Results

A total of 8289 polyps removed during screening colonoscopy were registered in the database between 2019 and 2023, from these 7187 were neoplastic (439 SMIC) and 1102 were non-neoplastic. Out of the 1095 serrated polyps 171 contained dysplasia. Non-neoplastic polyps had Kudo I pattern in 7.7%, Kudo II in 48.1%, Kudo III in 40.9%, Kudo IV in 3.2%, and Kudo V in 0.1% of the cases. Neoplastic lesions without submucosal invasion had Kudo I surface pattern in 2.0%, Kudo II in 7.5%, Kudo III in 71.2%, Kudo IV in 17.4%, and Kudo V in 1.7% of the cases, while in case of SMIC, the surface pattern was Kudo I in 0.2%, Kudo II in 0.7%, Kudo III in 15.7%, Kudo IV in 8.9%, and Kudo V in 74.5% of the cases.
Kudo I-II category showed moderate agreement with non-neoplastic lesions (κ=0.440), irrespective of lesion size and location, and timing of screening colonoscopy. The level of agreement was only slight for serrated lesions (κ=0.168). Kudo V category demonstrated substantial agreement (κ=0.722) with SMIC, irrespective of lesion size, location, and timing. SMICs could be identified based on Kudo V category with 74.5% sensitivity, 98.5% specificity, 73.0% positive and 98.6% negative predictive value.

Conclusion

This is the first real-world data obtained from screening colonoscopies of the Hungarian national colorectal screening program. Optical diagnosis might support the differentiation of neoplastic and non-neoplastic lesions and can be especially helpful in identifying SMICs that might require a different management approach.