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Distinct gene expression profiles between human preterm-derived and adult-derived intestinal organoids exposed to Enterococcus faecalis: a pilot study
  1. Andrea C Masi1,
  2. Tatiana Y Fofanova2,
  3. Christopher A Lamb3,4,
  4. Jennifer M Auchtung5,
  5. Robert A Britton2,
  6. Mary K Estes6,
  7. Sasirekha Ramani2,
  8. Simon J Cockell7,
  9. Jonathan Coxhead8,
  10. Nicholas D Embleton9,10,
  11. Janet E Berrington9,
  12. Joseph F Petrosino6,11,
  13. Christopher J Stewart1
  1. 1Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  2. 2Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
  3. 3Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  4. 4Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  5. 5Nebraska Food for Health Center and Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, USA
  6. 6Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
  7. 7Bioinformatics Support Unit, Newcastle University, Newcastle Upon Tyne, UK
  8. 8Bioscience Institute, Newcastle University, Newcastle upon Tyne, UK
  9. 9Newcastle Neonatal Service, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK
  10. 10Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
  11. 11Human Genome Sequencing Center, The Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to Dr Christopher J Stewart, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK; Christopher.Stewart{at}newcastle.ac.uk

http://dx.doi.org/10.1136/gutjnl-2021-326552

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    We read with interest the study by Kayisoglu et al1 comparing the gene expression between embryo-derived and adult-derived intestinal organoids. Some innate immune system genes were differentially expressed between the two organoid types, suggesting a potential role of exposure to the environment, including gut microbiota, in shaping the intestinal gene expression. In extremely preterm infants (<32 weeks gestation), microbial–host interaction at the epithelial surface has been associated with various morbidities including late onset sepsis and necrotising enterocolitis.2 Thus, preterm intestinal organoids may provide a specific and robust model for this population.

    We expand on the work carried by Kayisoglu et al1 by comparing whole transcriptome sequencing (RNA-sequencing) analysis performed on four preterm (23–32 weeks gestation) and five adult (30–60 years of age)3 intestinal organoid lines exposed to Enterococcus faecalis, a prevalent gut pathobiont.4 Human intestinal organoid lines were generated from preterm (surgical resection) and adult (biopsy) following the protocol described by Stewart et al.5 All specimens were from the ileum. Intestinal organoids were exposed to Enterococcus faecalis in form of monolayer using the organoid-anaerobe co-culture (OACC) model.6 All data are available at the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/), Accession: GSE161953.

    We first compared transcriptomic profiles from preterm and adult …

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    Footnotes

    • ACM and TYF are joint first authors.

    • Twitter @ACMasi10, @DrChrisLamb, @CJStewart7

    • Contributors AM and TYF conducted data analysis, interpretated results and drafted the initial manuscript. CAL, JMA, RAB, MKE, SR and JFP assisted with study design, provision of equipment, method optimisation, analysis and interpretation, and critically revising the article for important intellectual content. SJC and JC performed the RNA-sequencing and bioinformatics and assisted with analysis and interpretation, and drafting the article. NDE and JB assisted with study design, analysis and interpretation, and critically revising the article for important intellectual content. CS conceptualised the study, performed the experiments and assisted with data analysis/interpretation and drafting the manuscript. All authors approved the final manuscript.

    • Funding CS received funding from the Wellcome Institutional Strategic Support Fund (ISSF) and Newcastle University Academic Track scheme.

    • Disclaimer The funders had no role in the design and conduct of the study.

    • Competing interests TYF, JMA, RAB, MKE, JFP, CJS have filled a patent for the enteroid anaerobic co-culture system. CJS has received honorarium from Danone Nutricia.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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