Helicobacter pylori is a chronic bacterial pathogen that thrives in several regions of the stomach, causing inflammation that can vary by site and result in distinct disease outcomes. It is not known, however, whether the host-derived metabolites differ between the two main regions, the corpus and antrum. We thus characterized the metabolomes of mouse gastric corpus and antrum organoids and tissue. The secreted organoid metabolites differed significantly between the corpus and antrum in only seven metabolites: lactic acid, malic acid, phosphoethanolamine, alanine, uridine, glycerol, and isoleucine, with only lactic acid and phosphoethanolamine exceeding two-fold differences. Multiple chemicals were depleted upon H. pylori infection including urea, cholesterol, glutamine, fumaric acid, lactic acid, citric acid, malic acid, and multiple non-essential amino acids. Many are known H. pylori nutrients and did not differ between the two regions. When tissue was examined, there was little overlap with the organoid metabolites. The two tissue regions were distinct, however, including in antrum-elevated 5-methoxytryptamine, lactic acid, and caprylic acid, and corpus-elevated phospholipid products. Over an 8 month infection time course, the corpus and antrum remained distinct. The antrum displayed no significant changes, in contrast to the corpus which exhibited metabolite changes indicating stress, tissue damage, and depletion of key nutrients such as glutamine and fructose-6-phosphate. Overall, our results suggest the H. pylori preferentially uses carboxylic acids and amino acids in complex environments, and these are found in both the corpus and antrum.
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