Spatial and Temporal Analysis of the Stomach and Small-Intestinal Microbiota in Fasted Healthy Humans.
Although the microbiota in the proximal gastrointestinal (GI) tract have been implicated in health and disease, much about these microbes remains understudied compared to those in the distal GI tract. This study characterized the microbiota across multiple proximal GI sites over time in healthy individuals. As part of a study of the pharmacokinetics of oral mesalamine administration, healthy, fasted volunteers (n = 8; 10 observation periods total) were orally intubated with a four-lumen catheter with multiple aspiration ports. Samples were taken from stomach, duodenal, and multiple jejunal sites, sampling hourly (≤7 h) to measure mesalamine (administered at t = 0), pH, and 16S rRNA gene-based composition. We observed a predominance of Firmicutes across proximal GI sites, with significant variation compared to stool. The microbiota was more similar within individuals over time than between subjects, with the fecal microbiota being unique from that of the small intestine. The stomach and duodenal microbiota displayed highest intraindividual variability compared to jejunal sites, which were more stable across time. We observed significant correlations in the duodenal microbial composition with changes in pH; linear mixed models identified positive correlations with multiple Streptococcus operational taxonomic units (OTUs) and negative correlations with multiple Prevotella and Pasteurellaceae OTUs. Few OTUs correlated with mesalamine concentration. The stomach and duodenal microbiota exhibited greater compositional dynamics than the jejunum. Short-term fluctuations in the duodenal microbiota were correlated with pH. Given the unique characteristics and dynamics of the proximal GI tract microbiota, it is important to consider these local environments in health and disease states.IMPORTANCE The gut microbiota are linked to a variety of gastrointestinal diseases, including inflammatory bowel disease. Despite this importance, microbiota dynamics in the upper gastrointestinal tract are understudied. Our article seeks to understand what factors impact microbiota dynamics in the healthy human upper gut. We found that the upper gastrointestinal tract contains consistently prevalent bacterial OTUs that dominate the overall community. Microbiota variability is highest in the stomach and duodenum and correlates with pH.
['Seekatz|Anna M|AM|0000-0003-2586-7498', 'Schnizlein|Matthew K|MK|0000-0002-0797-8357', 'Koenigsknecht|Mark J|MJ|0000-0001-8287-784X', 'Baker|Jason R|JR|', 'Hasler|William L|WL|0000-0002-6158-2871', 'Bleske|Barry E|BE|0000-0002-4299-0829', 'Young|Vincent B|VB|0000-0003-3687-2364', 'Sun|Duxin|D|']
D000284:Administration, Oral D000293:Adolescent D000328:Adult D001419:Bacteria D005215:Fasting D005243:Feces D005260:Female D000068536:Firmicutes D000069196:Gastrointestinal Microbiome D064368:Healthy Volunteers D006801:Humans D006863:Hydrogen-Ion Concentration D007421:Intestine, Small D007441:Intubation, Gastrointestinal D016014:Linear Models D008297:Male D008875:Middle Aged D015661:Pasteurellaceae D012336:RNA, Ribosomal, 16S D062211:Spatio-Temporal Analysis D013270:Stomach D055815:Young Adult
stomach microbiota mesalamine pH small intestine