Biogeography of the stomach microbiota in humans, mice and gerbils indicates selective enrichment and depletion of specific bacterial taxa. Stomach enterogradients

Background: Despite increasing evidence for an important role of the stomach for the homeostasis of the entire gastrointestinal (GI) tract, the microbiota dynamics within the stomach and the upper GI tract remain poorly understood. Here we sought to determine the taxonomic bacterial biogeography of the upper GI tract by 16S rRNA gene amplicon sequencing, including different locations within the stomach (cardia, corpus and antrum), adjacent upstream (esophagus) and downstream (duodenum) locations, and luminal contents (aspirate) from humans as well as mice and gerbils. Results: Stomach aspirates and biopsies from Helicobacter pylori-negative individuals harbored a diverse microbiota; inter-individual variation was the dominant discriminating factor of taxonomic composition; and stomach locations showed little taxonomic variation but could be clearly separated from the esophagus. Compared to esophagus, relative abundances of Streptococcus were reduced and of Rothia mucilaginosa, Porphyromonas and Lachnospiraceae were increased in the stomach, all of which are typically described as orpharyngeal commensals. Human, mouse and gerbil samples were dominated by the same two bacterial orders Lactobacillales and Bacteroidales, but differed at the genus level, with human samples containing Streptococcus and Prevotella and animal samples Lactobacillus and an unknown genus of Bacteroidales family S24-7. The ratio of Lactobacillales and Bacteroidales varied considerably between individual patients and animals, independently of host-associated environmental or health parameters. Comparative analysis of esophageal biopsies and gastric aspirates indicated influx of streptococci from upstream GI locations into the stomach. 16S rRNA transcript analysis suggests that Bacteroidetes and Proteobacteria are enriched whereas Firmicutes and Actinobacteria are depleted in metabolically active microbiota fractions of the stomach. Conclusion: Our findings characterize the dynamic microbial ecosystem of the human stomach, which appears to be largely influenced by upstream GI locations but also to selectively enrich or deplete specific bacterial taxa during their passage to the intestine. Both similarities at the higher taxonomic levels and differences in the dominant bacterial genera were identified between humans and the two animal model species, mice and gerbils. Barcodes and primers can be extracted from the supplementary information online (allP_filtered.oligos; allM_filtered.oligos; allG_filtered.oligos).