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Original research
Alterations to the duodenal microbiota are linked to gastric emptying and symptoms in functional dyspepsia
  1. Erin R Shanahan1,2,
  2. Seungha Kang3,
  3. Heidi Staudacher1,2,
  4. Ayesha Shah2,4,
  5. Anh Do2,
  6. Grace Burns5,6,
  7. Veronique S Chachay7,
  8. Natasha A Koloski2,4,
  9. Simon Keely5,6,
  10. Marjorie M Walker8,9,
  11. Nicholas J Talley8,9,
  12. Mark Morrison10,
  13. Gerald J Holtmann2,4
  1. 1Faculty of Medicine and Faculty of Health & Behavioural Sciences, University of Queensland, Brisbane, Queensland, Australia
  2. 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
  3. 3The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
  4. 4Faculty of Medicine, Faculty of Health & Behavioural Sciences, and NHMRC Centre of Research Excellence Digestive Health, University of Queensland, Brisbane, Queensland, Australia
  5. 5School of Biomedical Sciences and Pharmacy and NHMRC Centre of Research Excellence Digestive Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia
  6. 6Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
  7. 7School of Human Movement and Nutrition Sciences, Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, Queensland, Australia
  8. 8Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
  9. 9School of Medicine and Public Health and NHMRC Centre of Research Excellence Digestive Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia
  10. 10The University of Queensland Diamantina Institute and NHMRC Centre of Research Excellence Digestive Health, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
  1. Correspondence to Professor Mark Morrison, The University of Queensland Diamantina Institute and NHMRC Centre of Research Excellence Digestive Health, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia; m.morrison1{at}uq.edu.au; Professor Gerald J Holtmann; g.holtmann{at}uq.edu.au

Abstract

Objective Functional dyspepsia (FD) is a complex disorder, with debilitating epigastric symptoms. Evidence suggests alterations in gastrointestinal (GI) motility, visceral hypersensitivity, permeability and low-level immune activation in the duodenum may play a role. However, we still have a relatively poor understanding of how these factors interact to precipitate the onset of FD symptoms which are frequently meal related. The duodenal microbiota, in combination with specific dietary substrates, may be important mediators in disease pathophysiology; however, these interlinked factors have not been thoroughly investigated in FD.

Design Eighty-six individuals (56 FD, 30 controls) undergoing endoscopy were consecutively recruited and underwent detailed clinical assessment, including upper GI symptoms, gastric emptying and dietary assessment. Duodenal biopsies were obtained aseptically, and the mucosa-associated microbiota (MAM) analysed via 16S rRNA gene amplicon sequencing.

Results The relative abundances of predominant members of the Firmicutes, Bacteroidota and Fusobacteriota phyla were linked to symptom burden in FD. Inverse relationships between the relative abundances of Streptococcus and Prevotella, and the relative abundance of Veillonella spp with gastric emptying time, were also observed. No significant differences in long-term nutrient intake or diet quality were found between FD and controls, and there appeared to be limited association between habitual diet and duodenal MAM profiles.

Conclusion This study suggests a link between the duodenal MAM, gastric emptying and FD symptoms, and this is largely independent of long-term dietary intake.

  • INTESTINAL MICROBIOLOGY
  • DIET
  • DUODENAL MUCOSA
  • GASTRIC EMPTYING

Data availability statement

Data are available on reasonable request. Online supplemental information included.

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Data availability statement

Data are available on reasonable request. Online supplemental information included.

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Footnotes

  • Twitter @hmstaudacher, @simonkeely

  • MM and GJH contributed equally.

  • Contributors ERS: study design, acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. SK: acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. HS: acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. AS: acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. AD: acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. GB: acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. VSC: acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. NAK: acquisition of data; drafting and critical revision of the manuscript for important intellectual content. SK: acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. MMW: study design, acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. NJT: study design, acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. MM: study design, acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content. GJH: study design, acquisition of data; analysis and interpretation of data; drafting and critical revision of the manuscript for important intellectual content.

  • Funding This study was funded by the National Health and Medical Research Council of Australia and The Princess Alexandra Hospital Research Foundation Australia.

  • Competing interests These authors disclose the following: NJT reports personal fees from Allakos, Aviro Health, from Antara Life Sciences, Arlyx, Bayer, Danone, Planet Innovation, Takeda, Viscera Labs, twoXAR, Viscera Labs, Dr Falk Pharma, Censa, Cadila Pharmaceuticals, Progenity Inc, Sanofi-aventis, Glutagen, ARENA Pharmaceuticals, IsoThrive, BluMaiden, HVN National Science Challenge, non-financial support from HVN National Science Challenge NZ, outside the submitted work; In addition, NJT has a patent Biomarkers of IBS licensed (#12735358.9 -1405/2710383 and (#12735358.9 -1405/2710384), a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, a patent Nestec European Patent licensed, and a patent Singapore Provisional Patent NTU Ref: TD/129/17 “Microbiota Modulation Of BDNF Tissue Repair Pathway” issued and copyright Nepean Dyspepsia Index (NDI) 1998 and Editorial: Medical Journal of Australia (Editor in Chief), Up to Date (Section Editor), Precision and Future Medicine, Sungkyunkwan University School of Medicine, South Korea, Med (Journal of Cell Press). NJT participates on committees for: Australian Medical Council (AMC) Council Member (2016-2019), MBS Review Taskforce (2016-2020), NHMRC Principal Committee, Research Committee (2016-2021), Asia Pacific Association of Medical Journal Editors (APAME) (current), GESA Board Member (2017-2019). NJT Misc: Avant Foundation (judging of research grants) (2019). NJT community and patient advocacy groups: Advisory Board, IFFGD (International Foundation for Functional GI Disorders). NJT acknowledges funding from the National Health and Medical Research Council (NHMRC) for the Centre for Research Excellence in Digestive Health. NJT holds an NHMRC Investigator grant. SK reports Grant/Research Support: National Health and Medical Research Council (Ideas Grant and Centre for Research Excellence) Viscera Labs (Research contract), Microba Life Science (Research contract). Consultant/Advisory Boards: Gossamer Bio (Scientific Advisory Board), Anatara Lifescience (Scientific Advisory Board), Microba Life Science (Consultancy). SK, MM, GLB, and NJT are co-inventors of “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, submitted 07/06/2021, via the University of Newcastle and UniQuest (University of Queensland) with PCT application 07/06/2022 (PCT/AU2022/050556). MM has received research grants from Soho Flordis International (SFI) Australia Research, Bayer Steigerwald Arzneimittelwerk and Yakult-Nature Global Grant for Gut Health; speaker’s honoraria, and travel sponsorship from Janssen Australia; consultancy fees from Sanofi Australia and Danone-Nutricia Australia; speaker honoraria and travel sponsorship from Perfect Company (China), and travel sponsorship from Yakult Inc (Japan). MM also acknowledges funding from NHMRC Australia, Australian Research Council, Princess Alexandra Hospital Research Foundation, Medical Research Futures Fund of Australia, Helmsley Charitable Trust via the Australasian Gastrointestinal Research Foundation, and United States Department of Defense. MM serves on the science advisory board (non-remunerated) for GenieBiome, Hong Kong. GJH reports to be on the advisory boards Australian Biotherapeutics, Glutagen, Bayer and received research support from Bayer, Abbott, Pfizer, Janssen, Takeda, Allergan. He serves on the Boards of the West Moreton Hospital and Health Service, Queensland, UQ Healthcare, Brisbane and the Gastro-Liga, Germany. He has a patent for the Brisbane aseptic biopsy device and serves as Editor of the Gastro-Liga Newsletter.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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