Introduction

With about 40% of adults infected with Helicobacter pylori (H. pylori), China has the highest number of gastric cancer (GC) cases worldwide.¹ Household transmission is the primary route for H. pylori infection,² and family-based testing and treatment has been proposed to mitigate GC cancer risk and prevent transmission.^1,3,4 A household-based transmission model for H. pylori would enhance understanding of H. pylori dynamics and inform intervention strategies. However, few models⁵ have been developed for H. pylori, and none incorporates household transmission.

Aims & Methods

We developed an agent-based household transmission model for H. pylori in China to study transmission patterns from 1990 to 2021. Building on our previous modeling framework,⁶ the model includes demographic and transmission components. The demographic simulation captures births, deaths, marriages, and mobility among youth, couples, and the elderly. Mobility parameters were calibrated using joint distributions of household size and generation from Chinese censuses of 1990, 2000, 2010, and 2020, allowing realistic household dynamics in China. In the transmission simulation, household and community transmissions were modeled using a susceptible-infected structure, applying density-dependent transmission within households and frequency-dependent transmission in the community. Contact rates, defined as the number of contacts adequate for transmission by an individual per year, were allowed to vary over time, and were dependent on the susceptible individual’s age. Contact rate variation was modeled by adjusting base rates with age- and year-specific multipliers, each following a continuously decreasing function. Simulations began in 1900, with the first 90 years as a burn-in period. Transmission parameters were calibrated and validated using data from our meta-analyses and a large national family-based survey from China in 2021⁷.

Results

The model aligned well with calibration targets. Key parameters and calibration results are summarized in the Table. Consistent with observed data, larger households had higher infection rates than smaller households. Three-generation households were more likely to have infected members than one- or two-generation households. Model calibration showed best fit when the within-household contact rate (0.2) was higher than the community rate (0.1), and when most infections occurred before age 20. Validation confirmed model accuracy: children’s infection probabilities were 31% with both parents infected, 21% with one infected parent, and 9% with neither. Our model found that family clustering became more pronounced in recent years with lower prevalence compared to earlier periods with higher prevalence.

Table. Calibration and validation results for the transmission model

Conclusion

We developed a novel agent-based model simulating community and household transmission of H. pylori. Our results confirm that household transmission is the primary infection route, and that childhood is the predominant period of acquisition. Notably, family clustering becomes more prominent in low-prevalence contexts. This model provides a valuable tool for evaluating various control strategies and offers insights difficult to obtain in real-world data. Future extensions could incorporate antibiotic resistance dynamics and adapt the model to other country contexts.

References

1. Ding, S.-Z. et al. Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition). Gut 71, 238–253 (2022).
2. Malfertheiner, P. et al. Helicobacter pylori infection. Nat. Rev. Dis. Primer 9, 1–24 (2023).
3. Chey, W. D. et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Off. J. Am. Coll. Gastroenterol. ACG 119, 1730 (2024).
4. Shah, S. C., Wang, A. Y., Wallace, M. B. & Hwang, J. H. AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review. Gastroenterology 168, 405-416.e1 (2025).
5. Rupnow, M. F. T., Shachter, R. D., Owens, D. K. & Parsonnet, J. A Dynamic Transmission Model for Predicting Trends in Helicobacter pylori and Associated Diseases in the United States. Emerg. Infect. Dis. 6, 228–237 (2000).
6. Blok, D. J. et al. The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study. PLoS Negl. Trop. Dis. 15, e0009279 (2021).
7. Zhou, X.-Z. et al. Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention. Gut 72, 855–869 (2023).B1

Clinical Case Summary

Introduction: Ustekinumab (UST), a human interleukin-12/23 monoclonal antibody, is approved for the treatment of moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Some patients may lose response to standard maintenance therapy. Optimization strategies, such as dose escalation and intravenous (IV) re-induction, have been explored in CD, but scarcely studied in UC.
Clinical Case: A 61-year-old woman, with grade III obesity, hypertension, and peripheral venous insufficiency, diagnosed with UC and associated peripheral arthropathy, was initially treated with high-dose corticosteroids (CTS) for a severe exacerbation. She developed CTS dependence and suffered an osteoporotic fracture.
A combined therapy with methotrexate and an accelerated infliximab (IFX) induction regimen was initiated, but a severe exacerbation occurred after the second induction dose. Despite an early third dose, clinical, biochemical and endoscopic (Mayo score 3) activity persisted.
The patient was swapped to UST with maintenance therapy every 4 weeks. After IV infusion, free-CTS clinical and biochemical (fecal calprotectin (FC) <10 ug/g) remission were achieved, but, over time, there was a loss of response, with a FC 4817 ug/g.
Given the initial positive response to IV UST infusion and insights from CD studies, a 520mg IV UST re-induction followed by 4-week maintenance dose was administered. Eight months later, the patient remains in free-CTS clinical remission, with improved arthralgia, biochemical remission (FC 80 ug/g) and endoscopic response.
Conclusions: This case highlights the potential efficacy of IV UST re-induction in recapturing remission in refractory UC. While recognized in CD, UST re-induction may prove beneficial for UC patients with loss of response to standard UST therapy, serving as an alternative before swapping. Further exploration through randomized, multicenter studies is crucial to assess the efficacy and safety of this strategy in UC patients.

Introduction

Accepted oncological principles advise enbloc, R0, excision of cancer to provide a cure. In Barrett’s neoplasia, this includes T1a and T1b disease, where histology is favorable. While treatment options include endoscopic mucosal resection (EMR) and submucosal endoscopic dissection (ESD), a mechanism for appropriate technique selection has not been described.

Aims & Methods

We conducted a prospective observational study to evaluate the performance of a selective resection algorithm for Barrett’s neoplasia (SRAB). To achieve an enbloc resection, ESD was selected if there was a suspicion for ≥T1a disease and the lesion was >15 mm (January 2017 to April 2023). This was compared with a conventional EMR predominant approach (CEA), where ESD was only performed in cases suspicious for deep submucosal invasion or T1b disease (February 2013 to December 2016). The primary outcome was curative oncologic resection (R0 resection with favorable histologic features).

Results

A total of 298 resections were performed in 298 patients (68 UEA, 230 SRAB). Median lesion size was 20 mm (IQR 15-30). T1a adenocarcinoma was identified in 83 (27.9%) and T1b in 58 (19.5%), of which 31 (10.4%) were SM1. Comparing T1a and T1b disease, the rate of enbloc resection (CEA 12 [46.2%] vs SRAB 103 [90.4%]; P<0.001), R0 excision (CEA 7 [26.9%] vs SRAB 86 [74.8%]; P<0.001) and curative resection (CEA 6 [23.1%] vs SRAB 58 [50.4%]; P=0.011) was higher in the SRAB group. Among all T1a and T1b-SM1 cases with favorable histology, which underwent ESD, 39/46 (84.8%) were R0 excisions and are likely cured. There were no significant differences in adverse events (P>0.788 for all).

Conclusion

A selective resection algorithm optimizes oncologic outcomes for Barrett’s adenocarcinoma and mitigates the risk of piecemeal resection of cancers.

Disclosure

Michael J. Bourke: Research Support: Olympus, Cook Medical, Boston Scientific.

Introduction

The pathophysiology of irritable bowel syndrome (IBS) includes alterations in gut-brain communication, gastrointestinal (GI) physiology and gut microbiota. The essential amino acid tryptophan (Trp) is metabolized in the gut to different classes of metabolites, including serotonin, kynurenine and indoles which have been implicated in the modulation of intestinal motility, immune function and pain sensation. Balanced Trp metabolism requires a complex host-microbiota interplay, which might be dysregulated in IBS. However, Trp metabolism is incompletely understood, and studies are needed to clarify its link with IBS and gastrointestinal physiology.

Aims & Methods

Aim: To profile fecal and circulating levels of Trp metabolites in IBS and explore relationships with oro-anal transit time (OATT) and symptoms.
Methods: We combined targeted and untargeted metabolomics to determine fecal and serum Trp metabolites in a cohort of healthy controls (HC; n=29) and IBS patients with predominant constipation (IBS-C; n=59), diarrhea (IBS-D; n=53) or mixed bowel habits (IBS-M; n=55). OATT was measured using radiopaque markers and participants completed questionnaires to assess GI symptom severity (GSRS-IBS), stool frequency and consistency (Bristol Stool Form Scale), non-GI somatic symptoms (PHQ-12), and symptoms of anxiety and depression (HAD). For correlation analyses, Spearman’s rho (r) was used.

Results

Levels of Trp did not differ significantly between HC and IBS subtypes. The Trp metabolite kynurenine, the microbially produced indole propionic acid (IPA) and the serotonin degradation metabolite 5-hydroxyindoleacetic acid (5-HIAA) were lower in IBS-C compared to HC and IBS-D. There were inverse correlations between OATT and both fecal (p<0.0001; r= -0.40) and circulating (p= 0.021; r= -0.17) Trp levels. Similarly, stool kynurenine and indoles were negatively correlated with OATT. Fecal but not circulating serotonin was positively correlated with OATT (p= 0.041; r= 0.14) while 5-HIAA showed a negative correlation (p<0.0001; r= -0.29), suggesting potential serotonin accumulation due to deficient degradation. In IBS patients, fecal Trp, 5-HIAA, IPA and kynurenine, correlated negatively with the proportion of hard stools (BSF1-2) and positively with the proportion of loose stools (BSF6-7). Finally, serotonin catabolites and IPA were negatively correlated with the severity of constipation and positively correlated with diarrhea. No statistically significant correlations were noted between these metabolites and abdominal pain, abdominal distension, early satiety, or postprandial fullness while bloating was positively correlated with circulating IPA (p= 0.018; r= 0.18). Additionally, we report a negative correlation between circulating serotonin with symptoms of depression and anxiety, which was not found for fecal serotonin. No significant correlations were noted with non-GI somatic symptoms.

Conclusion

Our results suggest that slower transit time may favour increased intestinal catabolism of Trp, directly or indirectly through its effects on the gut environment and the microbiota. In addition, we report an association of fecal Trp metabolites with bowel habits, in line with their relations to OATT. On the other hand, these same fecal metabolites did not correlate with other GI (i.e., pain and bloating) or non- GI symptoms. This study underscores the link between intestinal transit time and the regulation of host and microbial metabolites important for intestinal homeostasis.