Gastroduodenal diseases have prevailed for a long time and more so due to dominance of gut bacteria Helicobacter pylori in most of the cases. But habitation by other gut microbiota in gastroduodenal diseases and the relationship between Helicobacter pylori and gastrointestinal microbiota in different gastroduodenal diseases is somewhat being unravelled in the current times. For this systematic review, we did a literature search of various gastroduodenal diseases and the effect on gut microbiota pertaining to it. A search of the online bibliographic databases PUBMED and PUBMED CENTRAL was carried out to identify articles published between 1977 and May 2022. The analysis of these selected studies highlighted the inhabitation of other gut microbiota such as Fusobacteria, Bacteroidetes, Streptococcaceae, Prevotellaceae, Fusobacteriaceae, and many others. Interplay between these microbiota and H. pylori have also been noted which suggested that gastroduodenal diseases and gut microbiota are intertwined by a symbiotic association regardless of the H. pylori status. The relationship between the gut microbiota and many gastroduodenal diseases, such as gastritis, gastric cancer, lymphomas, and ulcers, demonstrates the dysbiosis of the gut microbiota in both the presence and absence of H. pylori. The evolving ways for eliminating H. pylori are provided along with inhibiting qualities of other species on H. pylori. Most significant member of our gut system is Helicobacter pylori which has been associated with numerous diseases like gastric cancer, gastritis, duodenal ulcer.

To investigate the association between use of nonsteroidal anti-inflammatory drugs (NSAID) and Helicobacter pylori infection, interactive effect of H. pylori infection and NSAID use on the development of peptic ulcer disease (PUD), and the effect of H. pylori eradication therapy on PUD development.

We performed a systematic literature search in EMBASE and PubMed for relevant articles published in English between January 1989 and August 2010, with the following MeSH and/or key words: non-steroidal anti-inflammatory drugs, or NSAIDs, Helicobacter pylori, or H. pylori, peptic ulcer disease or PUD, and randomized-control study or clinical trial. The meta-analysis was conducted using the Review Manager 4.2.2.

In the analysis of five studies, the pooled prevalence of H. pylori infection was 74.5% and 71.1% in NSAID users and non-NSAID users, respectively, (OR = 0.65; 95% CI: 0.35-1.20, p = .170). In the analysis of nine studies, the pooled prevalence of PUD in NSAID users was 31.2% and 17.9% in the presence and absence of H. pylori infection, respectively, (OR = 3.08; 95% CI: 1.26-7.55, p = .010). Moreover, in the analysis of seven studies, PUD developed in 6.4% and 11.8% of NSAID users with and without eradication therapy, respectively (OR = 0.50; 95% CI: 0.36-0.74, p < .001). The preventive effect of the eradication therapy was further revealed in NSAID-naive users (OR = 0.26; 95% CI: 0.14-0.49, p < .0001) and in the Asian population (OR = 0.30; 95% CI: 0.16-0.56, p < .001).

NSAID use is not associated with H. pylori infection in patients with PUD. PUD is more common in H. pylori positive than in negative NSAID users. Moreover, H. pylori eradication therapy reduces PUD incidence in NSAID users, especially in naive users and in the Asian population.

Heat shock proteins (HSPs) are crucial for the maintenance of cellular integrity during normal cell growth as well as pathophysiological conditions. While acting as molecular chaperones with their folding activities, HSPs play a cytoprotective role to rescue epithelial cells from several gastric damages including non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori. Since the exact relationship between HSP27 phosphorylation and biological function remains unknown in NSAID-induced gastropathy, we hypothesized that revaprazan, a novel acid pump antagonist, can secure significant cytoprotection from NSAID damages through HSP27 accentuation.

We evaluated protective actions of revaprazan against either in vivo animal model of indomethacin induced gastropathy or in vitro cell model focused on HSP27 expression and activation.

Indomethacin induced significant cytotoxicities accompanied with phosphorylated HSP27 and attenuated levels of HSP27 in the in vitro cell experiment and revaprazan administration protected stomach from indomethacin-induced gastric damages in accordance with HSP27 dephosphorylation in the in vivo animal experiment. HSP27 siRNA abolished these cytoprotective privileges of revaprazan. Indomethacin, 40 mg/kg, po, administration provoked significant levels of gastric damages accompanied with decrement in HSP27, while rats administrated with revaprazan prior to indomethacin imposed the accentuation of HSP27, of which levels were significantly correlated with the prevention of the indomethacin-induced gastric damages.

HSP27 phosphorylation with resultant decrease in HSP27 level was one of the mechanisms of indomethacin-induced cytotoxicity, of which post-translational modifications were prevented with revaprazan administration in the presence of indomethacin. Therefore, acid pump antagonist could be a choice for the prevention of NSAID-induced gastropathy backed up with distinctive cytoprotective action beyond acid suppressor.

Both the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, and infection with Helicobacter pylori are major causes of gastric ulcers. Although some clinical studies suggest that infection with H. pylori increases the risk of developing NSAID-induced gastric lesions, the molecular mechanism governing this effect is unknown. We recently found that in cultured gastric cells, expression of endoplasmic reticulum (ER) chaperones (such as 150-kDa oxygen-regulated protein (ORP150) and glucose-regulated protein 78 (GRP78)) is induced by NSAIDs and confers protection against NSAID-induced apoptosis, which is important in the development of NSAID-induced gastric lesions. In this study we have found that co-culture of gastric cells with H. pylori suppresses the expression of ER chaperones. This suppression was regulated at the level of transcription and accompanied by a reduction in the level of activating transcription factor 6 (ATF6), one of the transcription factors for ER chaperone genes. In vivo, inoculation of mice with H. pylori suppressed the expression of ER chaperones at gastric mucosa both with and without administration of indomethacin. Inoculation with H. pylori also stimulated formation of indomethacin-induced gastric lesions and mucosal cell death. In addition, we found that heterozygous ORP150-deficient mice are sensitive to the development of indomethacin-induced gastric lesions and mucosal cell death. The results of this study suggest that H. pylori exacerbates NSAID-induced gastric lesions through suppression of expression of ER chaperones, which stimulates NSAID-induced mucosal cell death.