Introduction

Pathogens can translocate from the gut lumen to the systemic circulation while gut microbiota play an important role in maintaining an immunologically balanced inflammatory response and protecting against colonisation by invasive pathogens. Studies showed that among people with liver cirrhosis, proton-pump inhibitor (PPI) users had a higher risk of spontaneous bacterial peritonitis (SBP). It has been hypothesised that PPI use can facilitate small intestinal bacterial overgrowth and related intestinal dysbiosis that lead to dysregulated bacterial translocation and subsequent SBP. However, the link between PPI use and systemic infectious complications secondary to bacterial translocation in non-cirrhotic patients is unclear.

Aims & Methods

This study aimed to investigate whether patients receiving PPI therapy have a higher risk for bloodstream infections (BSI) without an identifiable infectious focus, as an alternative indicator of BSI secondary to bacterial translocations. We conducted a hospital-based case–control study which enrolled all patients aged 20 years and older who developed BSI confirmed by two sets of positive blood culture and had inpatient care in Ichinomiya-Nishi Hospital in 2019. Patients’ data were collected from medical records, and bacterial translocation type (BT-type) BSI group were defined as those who had BSI without an identifiable focus of infection, whereas the others were classified control group. PPI use at BSI onset was considered the primary exposure of interest. To control for factors that were potentially associated with both PPI use and BSI, we retrieved data on the several factors and examined the potential confounders by using the Mantel–Haenszel stratified analyses. Logistic regression yielded adjusted odds ratios (OR) and 95% confidence intervals (CI) for BT-type BSI among PPI users and non-users. To address the possibility of outcome misclassification, we also conducted sensitivity analyses.

Results

We analysed data from 309 patients, including 66 cases (BT-type BSI group) and 243 controls. 152 patients (49%) were receiving continuous PPI therapy at BSI onset. The mean age was 78 years in both cases and controls. Patients on PPI therapy had a 2.4-fold higher risk of developing BT-type BSI compared to non-PPI-users after controlling for age, sex, the Charlson Comorbidity Index, liver cirrhosis, active gut disease, and onset location (OR: 2.41, 95% CI: 1.29–4.51). After adjustment, an association of PPI use with BT-type BSI (p=0.006) was observed. The results of the sensitivity analyses were consistent with the primary analysis.

Conclusion

PPI use is associated with higher risk of BSI without an identifiable infectious focus and therefore, PPI use may increase the risk of septic morbidity secondary to bacterial translocation.

References

1. MacFie J, O'Boyle C, Mitchell CJ, et al. Gut origin of sepsis: a prospective study investigating associations between bacterial translocation, gastric microflora, and septic morbidity. Gut 1999;45:223–8.
2. Alhumaid S, Al Mutair A, Al Alawi Z, et al. Proton pump inhibitors use and risk of developing spontaneous bacterial peritonitis in cirrhotic patients: A systematic review and meta-analysis. Gut Pathog 2021;13:17.
3. Lombardo L, Foti M, Ruggia O, et al. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2010;8(6):504-8.

Disclosure

Nothing to disclose

Introduction

Serum endomysial antibody (EMA) detection is still an important verification tool with high positive predictive value for coeliac disease (CeD) in patients positive with anti-transglutaminase antibody IgA (TGA) result or in seronegative cases with small intestinal villous atrophy. Moreover, EMA positivity is part of the non-invasive diagnostic criteria of CeD in children and adolescents with TGA+ results above 10 times of the upper limit of normal (>10xULN). EMA detections on the classical substrates, monkey oesophagus or human umbilical cord are less sensitive than TGA and both the preparation of the tissue slides and the reading are time-consuming and need expertise. Moreover, it is getting difficult to get commercial slides for the testing. Human umbilical cord vein-derived endothelial cells (HUVECs) produce in cell culture a regular extracellular matrix (ECM) resembling endomysial network with similar exposure of celiac-relevant transglutaminase epitopes as in tissue sections.

Aims & Methods

The aim of this study was to evaluate the diagnostic performance of EMA testing on HUVEC-ECM. Ninety new patients consecutively referred to our center between May –September 2023 in reason of positive coeliac antibody results in outside laboratories or by various rapid tests were prospectively tested for EMA-IgA on HUVEC-ECM prepared on 18-well plastic slides. Results were compared with those of our hospital’s TGA-IgA ELISA and EMA-IgA performed in 1:2.5 dilutions on a composite substrate containing monkey oesophagus, human umbilical cord and gut wall tissues.

Results

TGA-IgA, EMA-IgA on tissues and EMA-IgA on HUVEC-ECM were positive in 73, 62 and 67 samples with 94.4%, 92.9% and 95.7% accuracies for the final CeD diagnosis (non-invasive + biopsy-based), respectively. In 17 samples all three antibodies were negative; most of these patients had only TGA-IgG or DGP earlier.

Conclusion

The easily available novel HUVEC-ECM substrate provided high sensitivity and specifcity for EMA-IgA detection and also may improve the evaluation of coeliac autoimmunity when TGA is low positive or borderline.