Introduction

Gastric cancer (GC) is the 5^th most common cancer, but has been categorized as a neglected cancer by the World Health Organization.¹ Although the gastric precancerous process is well-characterized, the speed of the process, how it varies across populations and the exact impact of risk factors such as Helicobacter pylori (H. pylori) are not well understood. Understanding the natural history of GC can inform the design of preventive interventions across the globe.

Aims & Methods

We conducted a systematic review to pool the prevalences and progression rates of atrophic gastritis, gastric intestinal metaplasia and dysplasia. We included studies that reported histologically confirmed non-cardia gastric lesions and excluded studies that solely reported findings from high-risk groups such as those with a family history of GC, smokers or overweight individuals. Pooled random effect estimates of the prevalences and progression rates were computed. Studies were stratified as focused on low- (<6 GC cases per 100,000), medium- (6-15 per 100,000), or high-incidence (≥15 per 100,000) nations using definitions of rare cancers from the National Cancer Institute and a consortium from the European Union. Differences between these groups were statistically tested in a meta-regression. The estimates were stratified by active H. pylori infection status and compared over time.

Results

Our search query identified 5,841 publications. Of those, 209 met our inclusion criteria. The prevalences among countries with a low, medium and high GC incidence of atrophic gastritis (8% vs. 21% vs. 21%), intestinal metaplasia (11% vs. 18% vs. 21%) and dysplasia (1% vs. 2% vs. 3%) were substantially different (Table). When stratified for H. pylori, the difference in prevalence between countries with a differential GC risk disappeared, with the exception of H. pylori infected patients with intestinal metaplasia (20.6% vs. 21.3% vs 33.7%, Table). The prevalence of all three precursors decreased significantly over time. The pooled progression rates of atrophic gastritis, intestinal metaplasia and dysplasia to GC were 2.0, 2.8 and 14.6 per 1,000 person-years, respectively. There was no significant difference in the progression rates of the precursor lesions among countries with a low and medium-high GC incidence.

Table Pooled random effect estimates of the prevalence of GC precursor lesions, stratified by the study country’s level of GC incidence and H. pylori status.

Conclusion

The global disparity in GC incidence appears to be driven by a higher onset of precursors, rather than faster disease progression. These differences in precursor prevalence appear to be primarily driven by H. pylori. Additional data are needed to better understand how other factors, such as differences in H. pylori virulence, may contribute to the higher observed prevalence of intestinal metaplasia among H. pylori infected patients in high GC incidence countries. The pooled prevalences and progression rates in this study can be used to estimate the effect of GC prevention strategies, such as H. Pylori screen-and-treat in both a low- and high-risk setting.

References

1. IARC Helicobacter pylori Working Group. Helicobacter pylori Eradication as a Strategy for Preventing Gastric Cancer. Lyon, France: International Agency for Research on Cancer (IARC Working Group Reports, No. 8). 2014.

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

Irritable bowel syndrome (IBS) is considered a disorder of the altered microbiota-gut-brain axis, where gut dysbiosis and impaired central nervous system processing play important roles. The latter, in the form of depression, anxiety, and gastrointestinal-specific anxiety (GSA), frequently coexist and exacerbate IBS. Probiotics might be a promising therapeutic approach to treat IBS and coexisting depression, anxiety, and GSA.

Aims & Methods

The aim of the trial was to compare the impact of standard care combined with multi-strain probiotics with standard care alone on depression, anxiety, and visceral sensitivity in patients with diarrheal IBS (IBS-D). It was a 12-week randomized trial that included 108 patients with IBS-D that were divided into 2 groups: a control group (n = 51) receiving only standard care (diet, peppermint oil) and an experimental group (n = 57) receiving a combination of standard care (diet, peppermint oil) and the study probiotic (based on Lactobacillus, Streptococcus, Bifidobacterium, and Saccharomyces boulardii strains). Patient Health Questionnaire-9 (PHQ-9) and Beck’s Depression Inventory (BDI) were used to assess depression; the Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression; and the Visceral Sensitivity Index (VSI) was used to assess GSA.

Results

Baseline data were not different between the study groups (p> 0.05). After 12 weeks of treatment, PHQ-9, BDI, and anxiety subscale of HADS were not different between the study groups (p> 0.05), while the central tendency of the depression subscale of HADS in the control group was higher (3 (2-4)) than in the experimental group (3 (2-3)), p = 0.046. VSI was higher in the control group (31±5) compared to the experimental group (29±5.7), p = 0.032, after 12 weeks of trial.

Conclusion

In patients with IBS, additional prescribing of a multi-strain probiotic led to a decrease in depression according to HADS, as well as a reduction in GSA and visceral sensitivity assessed by VSI compared to IBS standard care alone.