Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome.

The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis.

Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors.

Background & Aims: In patients with autoimmune atrophic gastritis and achlorhydria, hypergastrinemia is associated with the development of type 1 gastric neuroendocrine tumors (gNETs). Twelve months of treatment with netazepide (YF476), an antagonist of the cholecystokinin B receptor (CCKBR or CCK2R), eradicated some type 1 gNETs in patients. We investigated the mechanisms by which netazepide induced gNET regression using gene expression profiling.

Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk.

Netazepide, a gastrin/cholecystokinin-2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis.

Aims: Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size of the largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalized circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the source of the tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type 1 gastric NETs.

Methods: After a mean 14 months off netazepide, 13 of the 16 patients took it for another 52 weeks.

Gastrin-induced miR-222 promotes gastric tumor development by suppressing p27kip1.

Background And Aims: Elevated circulating concentrations of the hormone gastrin contribute to the development of gastric adenocarcinoma and types-1 and 2 gastric neuroendocrine tumors (NETs). MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate proteins which in turn influence various biological processes. We hypothesised that gastrin induces the expression of specific gastric miRNAs within CCK2 receptor (CCK2R) expressing cells and that these mediate functionally important actions of gastrin.

Murine Models of Helicobacter (pylori or felis)-associated Gastric Cancer.

Gastric adenocarcinoma is the fifth most common cancer and third most common cause of cancer-related death in the world. The majority of these cancers develop in genetically susceptible individuals who are chronically infected with the Gram-negative bacterium Helicobacter pylori. Often these individuals have also been exposed to certain environmental factors that increase susceptibility, such as dietary components.

Patterns of genome evolution that have accompanied host adaptation in Salmonella.

Many bacterial pathogens are specialized, infecting one or few hosts, and this is often associated with more acute disease presentation. Specific genomes show markers of this specialization, which often reflect a balance between gene acquisition and functional gene loss. Within Salmonella enterica subspecies enterica, a single lineage exists that includes human and animal pathogens adapted to cause infection in different hosts, including S.

Dietary supplementation with soluble plantain non-starch polysaccharides inhibits intestinal invasion of Salmonella Typhimurium in the chicken.

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella.

Invasive non-typhoidal Salmonella typhimurium ST313 are not host-restricted and have an invasive phenotype in experimentally infected chickens.

Salmonella enterica serovar Typhimurium Sequence Type (ST) 313 is a major cause of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal reservoir has been identified, and it has been suggested that ST313 is adapted to humans and transmission may occur via person-to-person spread. Here, we show that ST313 cause severe invasive infection in chickens as well as humans.

Soluble plantain fibre blocks adhesion and M-cell translocation of intestinal pathogens.

Dietary fibres may have prebiotic effects mediated by promotion of beneficial bacteria. This study explores the possibility that soluble plant fibre may also improve health by inhibiting epithelial adhesion and translocation by pathogenic bacteria. We have focussed on soluble non-starch polysaccharide (NSP) from plantain bananas (Musa spp.