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Published November 2, 2021 | Published + Supplemental Material
Journal Article Open

Quantitative sequencing clarifies the role of disruptor taxa, oral microbiota, and strict anaerobes in the human small-intestine microbiome

Abstract

Background: 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. 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. Results: Using 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. Conclusion: This 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.

Additional Information

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Received 15 June 2021; Accepted 14 September 2021; Published 02 November 2021. We thank the Caltech Bioinformatics Resource Center for assistance with statistical analyses, Jenny Ji for related analyses and Natasha Shelby for contributions to writing and editing this manuscript. We acknowledge OpenMoji for use of the saliva and stool graphics in Fig. 1. We thank Stacy Weitsman, Walter Morales and Maria Jesus Villanueva-Milan from MAST for assistance with sample processing and data curation from the REIMAGINE study. We also thank the Gastroenterology team at Cedars-Sinai Medical Center for assistance with patient recruitment and endoscopy procedures. This work was supported in part by the Kenneth Rainin Foundation (2018-1207), the Jacobs Institute for Molecular Engineering for Medicine, and a National Institutes of Health Biotechnology Leadership Pre-doctoral Training Program (BLP) fellowship from Caltech's Donna and Benjamin M. Rosen Bioengineering Center (T32GM112592, to J.T.B.). The funders had no role in the design of the study, the collection, analysis, and interpretation of data, nor in writing the manuscript. Jacob T. Barlow and Gabriela Leite contributed equally to this work. Author Contributions: Conceptualization, J.T.B., G.L., R.M., M.P., and R.F.I.. Methodology, J.T.B., G.L., S.C., R.S., C.C.. Formal analysis, J.T.B.. Investigation, J.T.B, G.L., and A.E.R. Resources, G.L. Data curation, J.T.B., and G.L. Writing—original draft, J.T.B. Writing—review and editing, J.T.B., G.L., A.R., R.M., M.P., and R.F.I. Visualization, J.T.B. Supervision, M.P., and R.F.I. The author(s) read and approved the final manuscript. Ethics approval and consent to participate: The study was reviewed and approved by the Cedars-Sinai Medical Center IRB (Protocol #00035192). All participants provided written informed consent prior to participation. Consent for publication: Not applicable. Competing interests: The quantitative sequencing technology described in this publication is the subject of a patent application filed by Caltech. R.F.I. receives patent royalties from Bio-Rad related to droplet digital PCR.

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Additional details

Created:
August 22, 2023
Modified:
December 22, 2023