Abstract

BackgroundUpper gastrointestinal (GI) disorders and abdominal pain afflict between 12 and 30% of the worldwide population and research suggests these conditions are linked to the gut microbiome. Although large-intestine microbiota have been linked to several GI diseases, the microbiota of the human small intestine and its relation to human disease has been understudied. The small intestine is the major site for immune surveillance in the gut, and compared with the large intestine, it has greater than 100 times the surface area and a thinner and more permeable mucus layer.ResultsUsing quantitative sequencing, we evaluated total and taxon-specific absolute microbial loads from 250 duodenal-aspirate samples and 21 paired duodenum-saliva samples from participants in the REIMAGINE study. Log-transformed total microbial loads spanned 5 logs and were normally distributed. Paired saliva-duodenum samples suggested potential transmission of oral microbes to the duodenum, including organisms from the HACEK group. Several taxa, including Klebsiella, Escherichia, Enterococcus, and Clostridium, seemed to displace strict anaerobes common in the duodenum, so we refer to these taxa as disruptors. Disruptor taxa were enriched in samples with high total microbial loads and in individuals with small intestinal bacterial overgrowth (SIBO). Absolute loads of disruptors were associated with more severe GI symptoms, highlighting the value of absolute taxon quantification when studying small-intestine health and function.ConclusionThis study provides the largest dataset of the absolute abundance of microbiota from the human duodenum to date. The results reveal a clear relationship between the oral microbiota and the duodenal microbiota and suggest an association between the absolute abundance of disruptor taxa, SIBO, and the prevalence of severe GI symptoms.9CH1o1-EP8o4sE9CiFoJu4Video

Highlights

  • Upper gastrointestinal (GI) disorders and abdominal pain afflict between 12 and 30% of the worldwide population and research suggests these conditions are linked to the gut microbiome

  • We studied the microbiome of the duodenum and its potential relationship with health and disease in a cohort of 250 patients enrolled in the REIMAGINE study at Cedars-Sinai Medical Center

  • We show a clear relationship between the human oral microbiota and that of the duodenum

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Summary

Introduction

Upper gastrointestinal (GI) disorders and abdominal pain afflict between 12 and 30% of the worldwide population and research suggests these conditions are linked to the gut microbiome. The small intestine is the major site for immune surveillance in the gut, and compared with the large intestine, it has greater than 100 times the surface area and a thinner and more permeable mucus layer. In metabolic diseases or gastrointestinal (GI) disorders (e.g., irritable bowel syndrome [IBS], Crohn’s disease, malabsorption) that can cause GI symptoms, such as pain, bloating, and diarrhea, the small intestine instead of the colon may be the primary site of microbial interactions related to disease. Compared with the large intestine, the small intestine has several physiological differences that indicate its potential relevance for microbial interactions. The mucus layer of the small intestine is much thinner and more diffuse [4], potentially allowing closer interactions between microbes and the host. The small intestine is the main site for intestinal immune surveillance by lamina propria dendritic cells [5] and Peyer’s patches [6], contributing to the body’s response to both commensal and pathogenic microbes

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