Identification of glucagon like peptide-1 (GLP-1) in mice stomach.

Glucagon like peptide-1 (GLP-1) is a peptide hormone encoded by the pre-proglucagon gene that serves multiple physiological functions, including incretin action. While GLP-1 is primarily synthesized in the L cells of the lower intestine, recent findings indicate its presence in the stomachs of both rats and humans. However, the role of gastric GLP-1 in other species remains unclear. In this study, we aimed to identify GLP-1-producing cells and examine the localization of GLP-1 production in the mouse stomach. We found that pre-proglucagon mRNA was higher in the corpus than that in the antrum of the stomach. In addition, GLP-1 immunoreactive cells were found in the gastric mucosa, and their cell number was higher in the corpus than that in the antrum. Double immunofluorescence showed that some GLP-1 immunoreactive cells displayed somatostatin immunoreactivity, whereas did not co-localize with ghrelin and gastrin. Moreover, transmembrane G protein-coupled Receptor 5 (TGR5) agonist decreased pre-proglucagon mRNA expression in SG-1 cells in a concentration-dependent manner, and in vivo experiments showed a decrease in its mRNA levels in the gastric corpus but not in the antrum. This study marks the first report of GLP-1 production in the mouse stomach. Our findings suggest that gastric pre-proglucagon mRNA expression is regulated by a distinct mechanism compared to the L cells of the lower intestine.

Prox2 and Runx3 vagal sensory neurons regulate esophageal motility.

Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.

Impact of Physicochemical Modifications in Casein Promoted by UV-C on the Peptide Profile of Gastric Digestion and the Transepithelial Transport of Peptides.

Caseins are the main proteins in milk, and their structure and spatial conformation are responsible for their slow digestion rate. The release of bioactive and ß-casomorphin peptides from casein digestion may induce allergic responses during consumption. Spectroscopic techniques were used to observe the structural changes in casein conformation induced by Ultraviolet light irradiation (UV-C). Raman spectroscopy results showed more pronounced peaks at 618 and 640 cm-1 for phenylalanine and tyrosine moieties of the photolyzed micellar casein, respectively, suggesting changes in the micelle structure. The decrease in the intensity of Raman signals for tryptophan and tyrosine corroborates to the UV-C-induced modifications of the micelle structure. Particle size distribution showed a decrease in the average micelle size after 15 min of UV-C exposure, while low-temperature, long-time (LTLT) pasteurization led to the formation of large aggregates, as observed by atomic force microscopy. UV-C did not impact the formation or transport of peptides, as observed by using the Caco-2 cell as a model for peptide absorption. However, the absence of the opioid peptide SRYPSY from κ-casein and only 20% of the concentration of opioid peptide RYLGY were noted. This work demonstrated that UV-C can be utilized to induce the physicochemical modification of dairy products, promoting a higher digestion rate and reducing allergenicity.

Casein structures differently affect postprandial amino acid delivery through their intra-gastric clotting properties.

We aimed to assess if casein structure affects its digestion and its subsequent amino acid delivery kinetic. Higher nitrogen levels were recovered in dialysates after in vitro digestions of sodium caseinate (SC, formed of small aggregates) compared to micellar casein (MC, native form of casein) and calcium caseinate (CC, intermediate structure). Likewise, plasma indispensable amino-acid concentration peak was higher after SC compared to MC or CC ingestion in healthy volunteers in a randomized, double blind, cross-over study. In pigs, gamma-scintigraphy using labelled meals revealed that SC was mainly localized in the proximal part of the stomach whereas MC was distributed in the whole gastric cavity. Caseins were found in both solid and liquid phases and partly hydrolyzed casein in the solid phase shortly after SC drink ingestion. These data support the concept of slow (MC) and rapid (SC) casein depending of casein structure, likely due to their intra-gastric clotting properties.

Overexpression-Induced α-Synuclein Brain Spreading.

Interneuronal transfer of pathological α-synuclein species is thought to play an important role in the progressive advancement of Lewy pathology and increasing severity of clinical manifestations in Parkinson's and other diseases commonly referred to as synucleinopathies. Pathophysiological conditions and mechanisms triggering this trans-synaptic spreading bear therefore significant pathogenetic implications but have yet to be fully elucidated. In vivo experimental models support the conclusion that increased expression of intraneuronal α-synuclein can itself induce protein spreading throughout the brain as well as from the brain to peripheral tissues. For example, overexpression of α-synuclein targeted to the rodent dorsal medulla oblongata results in its transfer and accumulation into recipient axons innervating this brain region; through these axons, α-synuclein can then travel caudo-rostrally and reach other brain sites in the pons, midbrain, and forebrain. When protein overexpression is induced in the rodent midbrain, long-distance α-synuclein spreading can be followed over time; spreading-induced α-synuclein accumulation affects lower brain regions, including the dorsal motor nucleus of the vagus, proceeds through efferent axons of the vagus nerve, and is ultimately detected within vagal motor nerve endings in the gastric wall. As discussed in this review, animal models featuring α-synuclein overexpression not only support a relationship between α-synuclein burden and protein spreading but have also provided important clues on conditions/mechanisms capable of promoting interneuronal α-synuclein transfer. Intriguing findings include the relationship between neuronal activity and protein spreading and the role of oxidant stress in trans-synaptic α-synuclein mobility.

Effects of different grains on bacterial diversity and enzyme activity associated with digestion of starch in the foal stomach.

BACKGROUND: Compared with the stomach of ruminant cattle, the stomach of horse is small and mainly for chemical digestion, but the microorganisms in the stomach play an important role in maintaining the homeostasis of the internal environment. Due to the complexity of the microbes in the stomach, little is known about the diversity and structure of bacteria in the equine stomach. Grains are the main energy source for plant-eating livestock and energy is derived through enzymatic hydrolysis of grains into glucose or their microbial fermentation into Volatile fatty acids (VFA). However, the mechanism through which these ingested grains are chemically digested as well as the effect of these grains on the stomach remains elusive. This study explored the effects of feeding different grains (corn, oats, and barley) on bacterial diversity, structure, and composition in the foal's stomach content. Furthermore, the effects of different grains on the vitality of starch digestion-related stomach enzymes were investigated. RESULTS: No significant differences were observed (P > 0.05) in the bacterial rarefaction curves of Operational Taxonomic Units (OTUs) and diversity of the stomach microbiota in all foals. This study also revealed the statistical differences for Firmicutes, Cyanobacteria, Actinobacteria, Fibrobacteres, Lactobacillaceae, Streptococcaceae, Unidentified_Clostridiales, Prevotellaceae, Lactobacillus, Streptococcus, Unidentified_Cyanobacteria, Unidentified_Clostridiales, Lactococcus, Sphingomonas, Lactobacillus_hayakitensis, Lactobacillus_equigenerosi, and Clostridium_perfringens. The linear discriminant analysis effect size analysis revealed 9 bacteria at each classification level. The functional analysis of species information by using FAPROTAX software was able to predict 35 functions, and the top 5 functions were chemoheterotrophy, fermentation, animal_parasites_or_symbionts, nitrate_reduction, and aerobic_chemoheterotrophy. The study also revealed statistical differences for pH, glucose concentration, ß-amylase, maltase, and amylase. CONCLUSIONS: The different grains had no significant effect on the microbial diversity of the stomach content of the foal. However, the relative bacterial abundances differed significantly in response to different diets. Particularly, oats fed to the foals significantly increased the relative abundance of Firmicutes, Lactobacillaceae, Lactobacillus, and Lactobacillus_hayakitensis. The grain had no significant effect on the pH of the stomach content, glucose concentration, and enzyme viability in the foal.

The Effect of Dried Ginger (Gan Jiang) on Stomach Energy Metabolism and the Related Mechanism in Rats Based on Metabonomics.

Dried ginger is a commonly used stomachic. Dried ginger is often used as a gastric protector to treat stomach-related diseases. However, the effect of dried ginger on energy metabolism in stomach tissue of rats under physiological condition has not been studied. In this study, different doses of water extract of dried ginger were given to rats for 4 weeks. The activity of Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, SDH (succinate dehydrogenase) enzyme, ATP content, mitochondrial metabolic rate and mitochondrial number in stomach tissue of rats were measured. Analysis of potential biomarkers related to the effect of dried ginger on energy metabolism in stomach tissue of rats by metabonomics, and their metabolic pathways were also analyzed. The results revealed that there was no significant difference in Na+ -K+ -ATPase in high-dose group (GJH), medium-dose group (GJM) and low-dose group (GJL) compared to the Control group. The Ca2+ -Mg2+ -ATPase activity was significantly increased in stomach tissue of GJH group and GJM group, but there were no significant changes in stomach tissue of GJL group. The SDH activity and the ATP levels were significantly increased in stomach tissue of GJH group, GJM group and GJL group. The mitochondrial metabolic rate was significantly increased in GJL group, but there was no significant change in GJM group and was inhibited in GJH group. These effects might be mediated by arginine biosynthesis, glutathione metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, arginine and proline metabolism, purine metabolism pathway.

An inter-organ neural circuit for appetite suppression.

Glucagon-like peptide-1 (GLP-1) is a signal peptide released from enteroendocrine cells of the lower intestine. GLP-1 exerts anorectic and antimotility actions that protect the body against nutrient malabsorption. However, little is known about how intestinal GLP-1 affects distant organs despite rapid enzymatic inactivation. We show that intestinal GLP-1 inhibits gastric emptying and eating via intestinofugal neurons, a subclass of myenteric neurons that project to abdominal sympathetic ganglia. Remarkably, cell-specific ablation of intestinofugal neurons eliminated intestinal GLP-1 effects, and their chemical activation functioned as a GLP-1 mimetic. GLP-1 sensing by intestinofugal neurons then engaged a sympatho-gastro-spinal-reticular-hypothalamic pathway that links abnormal stomach distension to craniofacial programs for food rejection. Within this pathway, cell-specific activation of discrete neuronal populations caused systemic GLP-1-like effects. These molecularly identified, delimited enteric circuits may be targeted to ameliorate the abdominal bloating and loss of appetite typical of gastric motility disorders.

YAP1 regulates the self-organized fate patterning of hESC-derived gastruloids.

The gastrulation process relies on complex interactions between developmental signaling pathways that are not completely understood. Here, we interrogated the contribution of the Hippo signaling effector YAP1 to the formation of the three germ layers by analyzing human embryonic stem cell (hESC)-derived 2D-micropatterned gastruloids. YAP1 knockout gastruloids display a reduced ectoderm layer and enlarged mesoderm and endoderm layers compared with wild type. Furthermore, our epigenome and transcriptome analysis revealed that YAP1 attenuates Nodal signaling by directly repressing the chromatin accessibility and transcription of key genes in the Nodal pathway, including the NODAL and FOXH1 genes. Hence, in the absence of YAP1, hyperactive Nodal signaling retains SMAD2/3 in the nuclei, impeding ectoderm differentiation of hESCs. Thus, our work revealed that YAP1 is a master regulator of Nodal signaling, essential for instructing germ layer fate patterning in human gastruloids.

Fucoidan from Sargassum hemiphyllum inhibits infection and inflammation of Helicobacter pylori.

Having infected by Helicobacter pylori, the infection often leads to gastritis, gastric ulcer, or even gastric cancer. The disease is typically treated with antibiotics as they used to effectively inhibit or kill H. pylori, thus reducing the incidence of gastric adenoma and cancer to significant extent. H. pylori, however, has developed drug resistance to many clinically used antibiotics over the years, highlighting the crisis of antibiotic failure during the H. pylori treatment. We report here that the fucoidan from Sargassum hemiphyllum can significantly reduce the infection of H. pylori without developing to drug resistance. Fucoidan appears to be a strong anti-inflammation agent as manifested by the RAW264.7 cell model examination. Fucoidan can prohibit H. pylori adhesion to host cells, thereby reducing the infection rate by 60%, especially in post treatment in the AGS cell model assay. Mechanistically, fucoidan intervenes the adhesion of BabA and AlpA of H. pylori significantly lowering the total count of H. pylori and the level of IL-6 and TNF-α in vivo. These results all converge on the same fact that fucoidan is an effective agent in a position to protect the stomach from the H. pylori infection by reducing both the total count and induced inflammation.

Metabolism modulation in rat tissues in response to point specificity of electroacupuncture.

Zusanli (ST36) and Neiguan (PC6) are acupoints along two meridians. To demonstrate point specificity, we investigated the effects of ST36 and PC6 in electroacupuncture (EA)-treated rats. The rats were subjected to sham acupuncture at ST36 without electric stimulation, EA at ST36, or EA at PC6. Heart and stomach tissues were collected for metabolite profiling. Each type of stimulation resulted in a different metabolite composition in the rat heart and stomach tissues. In the heart tissues, EA at ST36 affected a wider range of metabolite pathways than did EA at PC6, whereas similar numbers of metabolites in the stomach tissues were affected by EA at ST36 and PC6. The pathways affected by EA at ST36 differed from those affected by EA at PC6, and a group of common metabolites were reversely regulated by these two acupoints. This study demonstrated point specificity effectively modulated metabolism in rat heart and stomach tissues. The results indicate that heart stimulation may be connected to the stomach through the pericardium meridian (as described in traditional Chinese medicine), explaining why acupuncture applied to the stomach meridian can be an alternative treatment for gastric and heart diseases.

In vitro simulated semi-dynamic gastrointestinal digestion: evaluation of the effects of processing on whey proteins digestibility and allergenicity.

The effect of thermal processing on digestibility of milk proteins should be better understood as this can greatly affect their immunoreactivity. The aim of this study was to evaluate the effects of thermal processing and lactosylation on digestibility and allergenicity, by comparing non heat-treated with industrially processed whey proteins. A semi-dynamic model was used to mimic the kinetics of digestion, and ELISA inhibition tests against human specific serum IgE were performed on the mass-spectrometry characterized products. A quicker gastric digestion of the industrially treated sample produced a lower immunogenic response in comparison with the raw sample, where intact conformational epitopes remained. In later digests, greater IgE reactivity was shown in the heat treated product, probably due to the release of linear epitopes, while at intestinal level the immunogenic response was negligible. Moreover, transepithelial transport of a reported ß-lactoglobulin-derived allergen, KIDALNENVLVL, produced during digestion was assayed. It was found that the epitope-belonging peptide could be transported through the cell monolayer, both in the native and mono-lactosylated forms, with a favored passage of the native peptide.

Intestinal gluconeogenesis shapes gut microbiota, fecal and urine metabolome in mice with gastric bypass surgery.

Intestinal gluconeogenesis (IGN), gastric bypass (GBP) and gut microbiota positively regulate glucose homeostasis and diet-induced dysmetabolism. GBP modulates gut microbiota, whether IGN could shape it has not been investigated. We studied gut microbiota and microbiome in wild type and IGN-deficient mice, undergoing GBP or not, and fed on either a normal chow (NC) or a high-fat/high-sucrose (HFHS) diet. We also studied fecal and urine metabolome in NC-fed mice. IGN and GBP had a different effect on the gut microbiota of mice fed with NC and HFHS diet. IGN inactivation increased abundance of Deltaproteobacteria on NC and of Proteobacteria such as Helicobacter on HFHS diet. GBP increased abundance of Firmicutes and Proteobacteria on NC-fed WT mice and of Firmicutes, Bacteroidetes and Proteobacteria on HFHS-fed WT mice. The combined effect of IGN inactivation and GBP increased abundance of Actinobacteria on NC and the abundance of Enterococcaceae and Enterobacteriaceae on HFHS diet. A reduction was observed in the amounf of short-chain fatty acids in fecal (by GBP) and in both fecal and urine (by IGN inactivation) metabolome. IGN and GBP, separately or combined, shape gut microbiota and microbiome on NC- and HFHS-fed mice, and modify fecal and urine metabolome.

Helicobacter pylori Targets in AGS Human Gastric Adenocarcinoma: In Situ Proteomic Profiling and Systematic Analysis.

BACKGROUND/AIM: Helicobacter pylori, a gram-negative bacterium, causes chronic stomach diseases in humans. Heat shock proteins (HSPs) are involved in cell integrity, cell growth, and gastric mucosa colonization by H. pylori. This study aimed to investigate HSP expression levels in H. pylori-infected gastric adenocarcinoma AGS cells. MATERIALS AND METHODS: We determined protein expression levels using iTRAQ proteomics analysis. We analyzed the possible network interactions for H. pylori targets in AGS cells using the Ingenuity Pathway Analysis (IPA) software. RESULTS: H. pylori-infected AGS cells potentially targeted EIF2 and BAG2 signaling pathways to regulate cell physiology. In addition, after 3, 6, and 12 h of infection, western blotting revealed significantly decreased HSP70 and HSP105 expression. CONCLUSION: H. pylori decreases HSPs in AGS gastric adenocarcinoma cells, and this is associated with the regulation of EIF2 and BAG2 signaling pathways.

Suction-Cup-Inspired Adhesive Micromotors for Drug Delivery.

Micromotors have opened novel avenues for drug delivery due to their capacity for self-propelling. Attempts in this field trend towards ameliorating their functions to promote their clinical applications. In this paper, an ingenious suction-cup-inspired micromotor is presented with adhesive properties for drug delivery in the stomach. The micromotors are fabricated by using hydrogel replicating the structure of suction-cup-like microparticles, which derive from self-assembly of colloidal crystals under rapid solvent extraction, followed by loading magnesium (Mg) in the bottom spherical surface. The Mg-loaded micromotors can realize spontaneous movement due to the continual generation of hydrogen bubbles in gastric juice. The combination of unique suction-cup-like structure with excellent motion performance makes the micromotor an ideal carrier for drug delivery as they can efficiently adhere to the tissue. Moreover, benefiting from the porous structure, the hydrogel micromotors exhibit a high volume-surface ratio, which enables efficient drug loading. It is demonstrated that the suction-cup-inspired micromotors can adhere efficiently to the ulcer-region in the stomach and release drugs due to their distinctive architecture and spontaneous motion, exhibiting desirable curative effect of gastric ulcer. Thus, the suction-cup-inspired micromotors with adhesive properties are expected to advance the development of micromotor in clinical applications.

Clinical Effect of Clarithromycin Combined with Tinidazole on Helicobacter pylori-Related Gastritis and Its Influence on COX-2 Expression.

Studies have shown that COX-2 expression is upregulated in gastric cancer (GC) as well as in precancerous lesions and in Helicobacter pylori-induced inflammation, suggesting that cyclooxygenase-2 (COX-2) may play an important role in gastric carcinogenesis. We attempted to investigate the role of clarithromycin with tinidazole on Helicobacter pylori-related gastritis from the aspects of clinical effect and COX-2 expression. From January 2016 to January 2019, 130 patients with Helicobacter pylori-related chronic gastritis were collected and grouped into the observation group (OG) and the control group (CG). Altogether, 80 patients in the OG were treated with clarithromycin with tinidazole, while 50 patients in the CG were treated with amoxicillin with metronidazole. Clinical symptom improvement time, content of COX-2 and B cell lymphoma-2 (BCL-2), content of inflammatory factors interleukin-1 (IL-1), IL-4, and C-reactive protein (CRP), expression level of nutritional indicators serum albumin (ALB), realbumin (PA), and transferrin (TF), clearance of Helicobacter pylori, total effective rate, and incidence of adverse reactions were detected. Compared with the CG, the OG had shorter clinical symptom improvement time, lower COX-2 and Bcl-2, lower expression of inflammatory factors IL-1, IL-4, and CRP, higher expression of nutritional indicators ALB, TF, and PA, higher clearance rate of Helicobacter pylori, higher total effective rate, and lower incidence of adverse reactions. Clarithromycin combined with tinidazole can effectively improve the clinical effect of Helicobacter pylori-related gastritis and reduce the expression level of COX-2.

Stomach secretes estrogen in response to the blood triglyceride levels.

Mammals receive body energy information to maintain energy homeostasis. Ghrelin, insulin, leptin and vagal afferents transmit the status of fasting, blood glucose, body fat, and food intake, respectively. Estrogen also inhibits feeding behavior and lipogenesis, but increases body fat mass. However, how blood triglyceride levels are monitored and the physiological roles of estrogen from the perspective of lipid homeostasis remain unsettled. Here, we show that stomach secretes estrogen in response to the blood triglyceride levels. Estrogen-secreting gastric parietal cells predominantly use fatty acids as an energy source. Blood estrogen levels increase as blood triglyceride levels rise in a stomach-dependent manner. Estrogen levels in stomach tissues increase as blood triglyceride levels rise, and isolated gastric gland epithelium produces estrogen in a fatty acid-dependent manner. We therefore propose that stomach monitors and controls blood triglyceride levels using estrogen, which inhibits feeding behavior and lipogenesis, and promotes triglyceride uptake by adipocytes.

Time to Classify Tumours of the Stomach and the Kidneys According to Cell of Origin.

Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By histological appearance the site of origin may often be confirmed. Using same treatment for tumours from the same organ is rational only when there is no principal heterogeneity between the tumours of that organ. Organ tumour heterogeneity is typical for the lungs with small cell and non-small cell tumours, for the kidneys where clear cell renal carcinoma (CCRCC) is the dominating type among other subgroups, and in the stomach with adenocarcinomas of intestinal and diffuse types. In addition, a separate type of neuroendocrine tumours (NETs) is found in most organs. Every cell type able to divide may develop into a tumour, and the different subtypes most often reflect different cell origin. In this article the focus is on the cells of origin in tumours arising in the stomach and kidneys and the close relationship between normal neuroendocrine cells and NETs. Furthermore, that the erythropoietin producing cell may be the cell of origin of CCRCC (a cancer with many similarities to NETs), and that gastric carcinomas of diffuse type may originate from the ECL cell, whereas the endodermal stem cell most probably gives rise to cancers of intestinal type.

A five-lncRNA model predicting overall survival in gastric cancer compared with normal tissues.

AIMS: In cancer research, normal tissues adjacent to the tumor are usually defined as controls to compare with tumor samples, in order to screen out cancer-related genes. Although there is no obvious difference in pathology between normal tissues adjacent to the tumor and healthy tissues, there are significant changes at the molecular level. We aim to explore more potential tumor biomarkers using healthy tissues as controls rather than normal tissues adjacent to the tumor. METHODS: Here we combine the Genotype-Tissue Expression project and The Cancer Genome Atlas for differential gene analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were applied in order to predict the biological effects of related lncRNAs. RESULTS: We established a 5-lncRNA prognosis model with an AUC value of 0.815. Pathway analysis indicated that 5-lncRNA mainly affected tissue carcinogenesis through PI3K-AKT signaling pathway, Focal adhesion, MAPK signaling pathway. CONCLUSION: The 5-lncRNA prognostic model we set up is more conducive to assess the overall survival time of gastric cancer patients.

Influence of Factors Altering Gastric Microbiota on Bariatric Surgery Metabolic Outcomes.

Little is known about the influence of gastric microbiota on host metabolism, even though the stomach plays an important role in the production of hormones involved in body weight regulation and glucose homeostasis. Proton pump inhibitors (PPIs) and Helicobacter pylori alter gut microbiota, but their impact on gastric microbiota in patients with obesity and the influence of these factors on the metabolic response to bariatric surgery is not fully understood. Forty-one subjects with morbid obesity who underwent sleeve gastrectomy were included in this study. The H. pylori group was established by the detection of H. pylori using a sequencing-based method (n = 16). Individuals in whom H. pylori was not detected were classified according to PPI treatment. Gastric biopsy specimens were obtained during surgery and were analyzed by a high-throughput-sequencing method. Patients were evaluated at baseline and 3, 6, and 12 months after surgery. ß-Diversity measures were able to cluster patients according to their gastric mucosa-associated microbiota composition. H. pylori and PPI treatment are presented as two important factors for gastric mucosa-associated microbiota. H. pylori reduced diversity, while PPIs altered ß-diversity. Both factors induced changes in the gastric mucosa-associated microbiota composition and its predicted functions. PPI users showed lower percentages of change in the body mass index (BMI) in the short term after surgery, while the H. pylori group showed higher glucose levels and lower percentages of reduction in body weight/BMI 1 year after surgery. PPIs and H. pylori colonization could modify the gastric mucosa-associated microbiota, altering its diversity, composition, and predicted functionality. These factors may have a role in the metabolic evolution of patients undergoing bariatric surgery. IMPORTANCE The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied. In this study, we highlight the impact of these factors on the gastric microbiota composition. Moreover, proton pump inhibitor treatment and the presence of Helicobacter pylori could have an influence on bariatric surgery outcomes, mainly on body weight loss and glucose homeostasis. Deciphering the relationship between gastric hormones and gastric microbiota and their contributions to bariatric surgery outcomes paves the way to develop gut manipulation strategies to improve the metabolic success of bariatric surgery.