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Gut Pathog. 2021 Feb 25;13(1):13. doi: 10.1186/s13099-021-00409-5.

Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn's disease.

Gut pathogens

Shijia Hu, Eileen Png, Michelle Gowans, David E H Ong, Paola Florez de Sessions, Jie Song, Niranjan Nagarajan

Affiliations

  1. Discipline of Orthodontics and Paediatric Dentistry, Faculty of Dentistry, National University of Singapore, 9 Lower Kent Ridge Road, Singapore, 119085, Singapore. [email protected].
  2. Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis St, Singapore, 138672, Singapore.
  3. Division of Gastroenterology & Hepatology, National University Hospital, 5 Lower Kent Ridge Rd, Singapore, 119074, Singapore.
  4. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

PMID: 33632307 PMCID: PMC7905567 DOI: 10.1186/s13099-021-00409-5

Abstract

BACKGROUND: This study aims to characterize, the gut and oral microbiome in Asian subjects with Crohn's disease (CD) using whole genome shotgun sequencing, thereby allowing for strain-level comparison.

METHODS: A case-control study with age, sex and ethnicity matched healthy controls was conducted. CD subjects were limited to well-controlled patients without oral manifestations. Fecal and saliva samples were collected for characterization of gut and oral microbiome respectively. Microbial DNA were extracted, libraries prepared and sequenced reads profiled. Taxonomic diversity, taxonomic association, strain typing and microbial gene pathway analyses were conducted.

RESULTS: The study recruited 25 subjects with CD and 25 healthy controls. The oral microbe Streptococcus salivarius was found to be enriched and of concordant strains in the gut and oral microbiome of Crohn's disease subjects. This was more likely in CD subjects with higher Crohn's Disease Activity Index (184.3 ± 2.9 vs 67.1 ± 82.5, p = 0.012) and active disease status (Diarrhoea/abdominal pain/blood-in-stool/fever and fatigue) (p = 0.016). Gut species found to be significantly depleted in CD compared to control (Relative abundance: Median[Range]) include: Faecalibacterium prausnitzii (0.03[0.00-4.56] vs 13.69[5.32-18.71], p = 0.010), Roseburia inulinivorans (0.00[0.00-0.03] vs 0.21[0.01-0.53], p = 0.010) and Alistipes senegalensis (0.00[0.00-0.00] vs 0.00[0.00-0.02], p = 0.029). While Clostridium nexile (0.00[0.00-0.12] vs 0.00[0.00-0.00], p = 0.038) and Ruminococcus gnavus (0.43[0.02-0.33] vs 0.00[0.00-0.13], p = 0.043) were found to be enriched. C. nexile enrichment was not found in CD subjects of European descent. Microbial arginine (Linear-discriminant-analysis: 3.162, p = 0.001) and isoprene (Linear-discriminant-analysis: 3.058, p < 0.001) pathways were found at a higher relative abundance level in gut microbiome of Crohn's disease.

CONCLUSIONS: There was evidence of ectopic gut colonization by oral bacteria, especially during the active phase of CD. Previously studied gut microbial differences were detected, in addition to novel associations which could have resulted from geographical/ethnic differences to subjects of European descent. Differences in microbial pathways provide possible targets for microbiome modification.

Keywords: Crohn’s disease; Gastrointestinal microbiome; Metagenomics; Oral microbiome

References

  1. Digestion. 2016;93(1):59-65 - PubMed
  2. J Dent Res. 2020 Aug;99(9):1021-1029 - PubMed
  3. Inflamm Bowel Dis. 2011 Jan;17(1):179-84 - PubMed
  4. Nat Rev Gastroenterol Hepatol. 2015 Dec;12(12):720-7 - PubMed
  5. JAMA. 2013 May 22;309(20):2150-8 - PubMed
  6. Nat Methods. 2015 Oct;12(10):902-3 - PubMed
  7. Infect Immun. 2013 Oct;81(10):3500-2 - PubMed
  8. Genome Res. 2017 Apr;27(4):626-638 - PubMed
  9. J Crohns Colitis. 2015 May;9(5):398-403 - PubMed
  10. Gut. 2005 Feb;54(2):237-41 - PubMed
  11. Gut Microbes. 2018 Jan 2;9(1):38-54 - PubMed
  12. Aliment Pharmacol Ther. 2015 Feb;41(4):329-41 - PubMed
  13. Cell Host Microbe. 2014 Mar 12;15(3):382-392 - PubMed
  14. World J Gastroenterol. 2014 Feb 7;20(5):1192-210 - PubMed
  15. Inflamm Bowel Dis. 2012 May;18(5):935-42 - PubMed
  16. PLoS Comput Biol. 2012;8(6):e1002358 - PubMed
  17. Inflamm Bowel Dis. 2009 Aug;15(8):1183-9 - PubMed
  18. Gastroenterology. 1976 Mar;70(3):439-44 - PubMed
  19. Inflamm Bowel Dis. 2019 Oct 18;25(11):1751-1763 - PubMed
  20. Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):12672-12677 - PubMed
  21. mBio. 2016 Sep 20;7(5): - PubMed
  22. Cell. 2020 Jul 23;182(2):447-462.e14 - PubMed
  23. Elife. 2019 Feb 12;8: - PubMed
  24. BMC Bioinformatics. 2014 Jun 12;15:182 - PubMed
  25. Immunology. 2017 Aug;151(4):363-374 - PubMed
  26. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6 - PubMed
  27. Cell Host Microbe. 2007 Aug 16;2(2):119-29 - PubMed
  28. Inflamm Bowel Dis. 2015 Dec;21(12):2797-805 - PubMed
  29. Nature. 2019 May;569(7758):655-662 - PubMed
  30. Nat Microbiol. 2018 Mar;3(3):337-346 - PubMed
  31. Lancet. 2012 Nov 3;380(9853):1590-605 - PubMed
  32. Science. 2017 Oct 20;358(6361):359-365 - PubMed
  33. Amino Acids. 2004 Jul;26(4):321-9 - PubMed
  34. Environ Microbiol. 2015 Mar;17(3):699-710 - PubMed
  35. Sci Rep. 2016 Mar 15;6:23075 - PubMed
  36. Genome Biol. 2012 Apr 16;13(9):R79 - PubMed
  37. Gigascience. 2017 Jul 1;6(7):1-11 - PubMed
  38. DNA Res. 2014 Feb;21(1):15-25 - PubMed
  39. Stand Genomic Sci. 2012 Jul 30;6(3):1-16 - PubMed
  40. Gastroenterology. 2008 Dec;135(6):1907-13 - PubMed
  41. Front Microbiol. 2018 May 30;9:1136 - PubMed
  42. Gut Pathog. 2018 Oct 10;10:44 - PubMed
  43. Cell Host Microbe. 2011 May 19;9(5):390-403 - PubMed
  44. PLoS One. 2014 Mar 07;9(3):e90981 - PubMed

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