Qualitative and Quantitative DNA- and RNA-Based Analysis of the Bacterial Stomach Microbiota in Humans, Mice, and Gerbils.

Clinical interventions in the stomach have been linked to fecal microbiota alterations, suggesting a function of the stomach in gastrointestinal (GI) homeostasis. We sought to determine the taxonomic bacterial biogeography of the upper GI tract, including different sites within the human stomach (cardia, corpus, and antrum), adjacent upstream (esophagus) and downstream (duodenum) locations, and luminal contents (aspirate), as well as whole-stomach samples from mice and gerbils. Qualitative and quantitative DNA- and RNA-based taxonomic microbiota analyses were combined to study the relationship of relative and absolute bacterial abundances and transcriptionally active bacterial microbiota components in the stomach of humans and mice. Stomach microbiota compositions resembled those of esophagus and duodenum. However, along the descending GI tract, the relative abundances of specific oropharyngeal commensals decreased () or increased (Rothia mucilaginosa, , and ). Furthermore, the compositional similarity (weighted UniFrac) between stomach aspirates and esophageal biopsy samples increased with gastric relative abundance. In both human aspirate and mouse stomach samples, were more abundant among transcriptionally active bacteria than . The relative abundance of in the stomach was negatively correlated and that of was positively correlated with absolute bacterial abundance, suggesting a disproportionate increase of over at higher bacterial densities. Human, mouse, and gerbil stomach samples showed similarities at higher taxonomic levels but differences at lower taxonomic levels. Our findings suggest selective enrichment and depletion of specific bacterial taxa in the stomach and being transcriptionally more active than that increase in relative abundance with total bacterial load. Clinical stomach interventions, such as acid inhibition or bypass surgery, have been linked to fecal microbiota alterations. We demonstrate that the stomach microbiota largely overlaps those of adjacent gastrointestinal locations and identify gradual decreases and increases in the relative abundances of specific bacteria within the stomach, suggesting selective enrichment and depletion. Moreover, similarities between stomach and esophagus samples are proportional to the concentrations of () in the stomach. The relative abundance of in the stomach, compared to that of , is increased in RNA relative to DNA, indicating higher transcriptional activity. Moreover, increased absolute bacterial loads are associated with decreased relative abundance of and higher relative abundance of . Our findings characterize the stomach microbiota as influenced by influx against a background of transcriptionally more active Human, mouse, and gerbil stomach microbiotas differ at lower taxonomic levels, which might affect the utility of these model organisms.