Introduction

Irritable Bowel Syndrome (IBS) is a chronic disorder of the gut-brain interaction characterized by visceral hypersensitivity. There is growing evidence underscoring the beneficial impact of probiotics and postbiotics with psychobiotics properties in relieving stress-related gastrointestinal disorders in humans especially in patients suffering from IBS. We have previously shown that high GABA-producer L. lactis CNCM I-5388 exerts antinociceptive properties after 5- and 10-days oral treatment in an IBS-like rat model. We demonstrated, using both mutant L. lactis ΔgadB strains and GABA_B receptor antagonist that these antinociceptive properties were dependent on the GAD-enzymatic activity of L. lactis and mediated by host’s GABA_B receptors. In addition, we have shown that CNCM I-5388 displayed a high cell-bound GAD activity and survival in vitro under HCl-mediated acidic stress.

Aims & Methods

In this work, we were interested in studying the GABA-producer L. lactis CNCM I-5388 as an active-enzyme postbiotic to relieve visceral hypersensitivity mediated by a psychological stress.
L.lactis CNCM I-5388 was inactivated by ethanol (EtOH) while maintaining its GAD activity. Female Wistar rats were treated orally for 1, 5 or 10 days by the EtOH-treated nonviable L.lactis CNCM I-5388 form or the viable L. lactis CNCM I-5388 or vehicle. Visceral sensitivity in response to colorectal distension was measured by electromyography before and after partial restraint stress (PRS). GABA levels were quantified by HPLC both in the stomach collected from rats and in the gastric compartment of the TIM-1 human gut model in fed state.

Results

A daily treatment for 5 and 10 days by L. lactis CNCM I-5388 both in its viable and nonviable forms counteracted visceral hypersensitivity-induced by PRS in response to colorectal distension. However, after a single administration only viable L. lactis CNCM I-5388 tended to reduce visceral hypersensitivity. After 5-days treatment, the production of GABA within the stomach was enhanced in stressed rats treated with the viable or nonviable L. lactis CNCM I-5388 form. This increase was confirmed by using the TIM-1 human gut model.

Conclusion

Our results highlight that a postbiotic with an active-GAD of L. lactis CNCM I-5388, similarly to its viable psychobiotic form, exerts visceral antinociceptive properties in an IBS-like rat model. These effects are associated with GABA production in the stomach where the low pH promotes GAD activity. From a clinical point of view, this “active GAD-bag” concept offers a new therapeutic perspective in the management of visceral pain in IBS patients with a superior safety profile compared with GABA-producing pyschobiotics that could acquire antibiotic resistance and virulence factors in chronic use.

Disclosure

Jonna Koper, Elyse Parent, Nabil Bosco, Nathalie Ballet and Sophie Legrain-Raspaud are full-time employees of Lesaffre. None of the authors have a conflict of interest.

Introduction

Recents meta-analyses have shown that Tegoprazan (Tego) could be equal or superior to proton pump inhibitors in the eradication of Helicobacter pylori (HP). However, virtually all primary studies have been conducted in Asian populations, so validation in other regions is required.

Aims & Methods

Aim: To assess the efficacy and safety of Tego compared to Esomeprazole (Eso) in Latin population. Methods: We studied 117 consecutive treatment-naive HP infected patients [51.04±12.11 (48.85-53.24) years, 75% females] evidenced by endoscopic biopsy. Patients were randomized to receive either Tego (50 mg) or Eso (40 mg), both in combination with Amoxicillin (1 g) and Clarithromycin (500 mg), all administered twice daily for 14 days. Treatment efficacy was assessed using a urea breath test performed 35±2 days post-therapy. Treatment safety was monitored by recording adverse events. Additionally, dyspeptic symptoms, general laboratories and quality of life (SF-36 questionnaire) were assessed. Data expressed mean±SD and 95% CI or percentages, while statistical differences were evaluated with the unpaired and paired Student t test or the chi-square test, as appropriate. Alpha = 0.05.

Results

There were no differences between Tego and Eso groups in age [51±12.14 (47.79-54.21) vs. 51.08±12.28 (48.02-54.14) years respectively, p= 0.97] or sex (75.4% vs. 74.6% women respectively, p=0.76). Tego and Eso groups showed similar efficacy (94.55% vs 93.55% respectively, p=0.82) and adverse events (14.55% vs 22.58% respectively, p=0.26). Main symptoms in Tego group were diarrhea (n=4) and headache (n=2) meanwhile Eso group referred diarrhea (n=4) and abdominal pain (n=4). All adverse events were mild and suspend treatment was not required. Dyspeptic symptoms decreased after treatment in both Tego (78.88% vs 45.45%, p=0.0004) and Eso (79.03% vs 46.77%, p=0.0002) groups but there were no differences before (p=0.9108) and after (p=0.8864) treatment between them. There were no differences in the 18 components of the general laboratories (all in normal range) between groups before and after treatment. Physical component summary (CS) improved post treatment in both Tego [48.56±13.96 (44.87-52.25) vs 51.83±13.17 (48.35-55.31), p=0.03] and Eso [46.95±11.35 (44.13-49.78) vs 52.29±13.22 (49-55.58), p=0.01] groups. Mental CS showed no differences after treatment en Tego [47.35±5.99 (45.77-48.94) vs 47.8±6.48 (46.09-49.51), p=0.62] nor Eso [47.51±6.67 (45.86-49.17) vs 47.82±5.39 (46.47-49.16), p=0.78] groups. There was no difference in physical or mental CS between Tego and Eso groups before (p=0.49 and p=0.85, respectively) or post treatment (p=0.89 and p=0.98, respectively) Table 1.

Table 1. The 8 domains of SF-36 in both groups (*p<0.05 vs basal)

Conclusion

Our work shows that Tegoprazan is equally effective and safe as Esomeprazole for triple therapy to eradicate Helicobacter pylori in Latin population. We also found that eradication treatment improves general health, physical functioning, and physical component summary, which warrants further investigation. Clinical Trials registration: NCT06318104.

References

(/10.1080/14787210.2025.2459722) (10.1002/jgh3.70134)

Disclosure

We would like to thank Carnot Laboratories for providing tegoprazan for this study.

Introduction

Helicobacter pylori (H. pylori) antibiotic resistances are the leading cause for unsuccessful eradication therapy. After one or more failures, the chance of encountering secondary antibiotic resistances increases. The aim of this study was to characterize genotypic secondary resistances in a cohort of Southern Italy H. pylori patients with at least one previous failure.

Aims & Methods

Patients with at least one previous eradication failure collected stool samples by a dedicated kit (THD fecal testTM) and bacterial DNA was extracted and amplified by RT-PCR. Resistance to clarithromycin, amoxicillin, metronidazole, levofloxacin and tetracycline was assessed by high-resolution melting curve.

Results

We enrolled 50 patients. The 72% failed one previous antibiotic course, the 16% two, the 10% three and the 2% four. The rate of secondary antibiotic resistance was 16% for clarithromycin, 18% for metronidazole, 14% for amoxicillin, 14% for levofloxacin and 2% for tetracycline. Multi-resistance was detected in 9 patients (18%) and double resistance to clarithromycin + metronidazole was the most common one (n = 5). Among patients with a previous failure to an amoxicillin-containing regimen, amoxicillin resistance was found in 4 out of 20 (20%). Among patients with a previous failure to a clarithromycin-containing regimen, resistance to such antibiotic was detected in 6 out of 19 (31.6%). Among patients with a previous failure to a metronidazole-containing regimen (n = 21), metronidazole resistance was found in 3 cases (14.3%). A failed levofloxacin-based therapy was given in 3 patients, but in none of them resistance was found (0%). Finally, among patients with a previous failure to a tetracycline-containing therapy, resistance to such antibiotic was detected in 1 out of 12 (8.3%)

Conclusion

In conclusion, our data seem to show that, despite secondary resistances are not so high, a resistance to clarithromycin could be very likely related to previous exposure to this antibiotic.

Introduction

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disorder of the bile ducts, associated with significant morbidity and an increased risk of malignancy. Preclinical studies in mice deficient in the multidrug resistance protein 2 (Mdr2−/−) have demonstrated that the integrin αvβ6 plays a critical role in biliary fibrosis by activating latent transforming growth factor (TGF)-β1, the main profibrotic cytokine in the liver. Moreover, several studies have shown that autoantibodies against integrin αvβ6 exhibit good diagnostic accuracy in ulcerative colitis (UC). The aim of this meta-analysis is to evaluate the diagnostic performance of anti-integrin αvβ6 autoantibodies in PSC.

Aims & Methods

A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases (PubMed, Scopus, ScienceDirect, and the Cochrane Library) were systematically searched up to February 2025. Eligible studies included those involving patients with PSC as well as non-PSC control groups, in which the overall sensitivity and specificity of serum anti-integrin αvβ6 autoantibodies for the diagnosis of PSC were reported. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using a random-effects model. Subgroup analyses were conducted based on the presence or absence of concomitant UC. Meta-analyses were performed using RevMan version 5.4.

Results

Four studies, comprising a total of 1,228 participants, met the predefined eligibility criteria. All studies defined the positivity threshold as the mean value in control groups plus three standard deviations (SD). The pooled sensitivity and specificity for the diagnosis of PSC were 0.679 (95% CI: 0.670–0.689) and 0.940 (95% CI: 0.939–0.941), respectively, with high heterogeneity (I² = 99%).
In the subgroup analysis, the sensitivity and specificity of the test for diagnosing PSC in the absence of concomitant UC were 0.075 (95% CI: 0.071–0.080) and 0.940 (95% CI: 0.939–0.941), respectively. In contrast, in the subgroup of patients with both PSC and UC, sensitivity reached 0.960 (95% CI: 0.959–0.961), while specificity was 0.720 (95% CI: 0.713–0.727).
Sensitivity analyses performed to explore the observed heterogeneity revealed that exclusion of one study (Bloeman, 2024) significantly improved diagnostic performance across all subgroups, with a pooled sensitivity of 0.831 (95% CI: 0.8236–0.8384) and specificity of 0.946 (95% CI: 0.9451–0.9468).

Conclusion

Serum anti-integrin αvβ6 autoantibodies demonstrate diagnostic value in PSC, with consistently high specificity across all patient groups and notably high sensitivity in those with concomitant ulcerative colitis. The high specificity supports a strong negative predictive value. Given the supporting preclinical evidence, integrin αvβ6 warrants further investigation not only as a diagnostic biomarker but also as a potential therapeutic target.

Disclosure

​No conflict of ​Interest