SpringerLink
Log in

Features of the gut prokaryotic virome of Japanese patients with Crohn’s disease

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

A Correction to this article was published on 28 June 2022

This article has been updated

Abstract

Background/aims

The gut virome is mainly composed of bacteriophages and influences gut homeostasis and pathogenic conditions. In this study, we analyzed the gut prokaryotic virome in Japanese patients with Crohn’s disease (CD).

Materials/methods

We collected 19 fecal samples from CD patients and 16 samples from healthy controls. The gut bacteriome was analyzed by 16S rRNA gene sequencing and the virome was profiled by shotgun metagenomic sequencing.

Results

Despite no differences in richness and evenness, there was a significant difference in the overall structure of the gut virome between CD patients and controls (P = 0.013). CrAssphage and Staphylococcus virus, belonging to the order Caudovirales, were dominant in the gut virome of controls and CD patients. The abundance of crAssphage was significantly greater in CD patients than controls (P = 0.021). Lactococcus, Enterococcus and Lactobacillus phages were present only in CD patients, while Xanthomonas and Escherichia phages were unique to the controls. In the gut bacteriome of CD patients, richness and evenness were significantly lower, and a significant difference in the overall structure was observed between groups (P = 0.014). The gut bacteriome of CD patients was characterized by a decrease of the genera Faecalibacterium, Roseburia, and Ruminococcus and an increase of the family Enterobacteriaceae. There were more significant correlations between viruses and bacteria in CD patients than controls.

Conclusions

The gut virome of CD patients was distinct from that of healthy controls in a Japanese population. An altered gut virome may be one of the factors associated with the bacterial dysbiosis of CD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Change history

References

  1. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–34.

    Article  CAS  PubMed  Google Scholar 

  2. Kaplan GG, Ng SC. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology. 2017;152(313–321):e312.

    Google Scholar 

  3. Chan HC, Ng SC. Emerging biologics in inflammatory bowel disease. J Gastroenterol. 2017;52:141–50.

    Article  CAS  PubMed  Google Scholar 

  4. Human Microbiome Project C. Structure. function and diversity of the healthy human microbiome. Nature. 2012;486:207–14.

    Article  CAS  Google Scholar 

  5. Human Microbiome Project C. A framework for human microbiome research. Nature. 2012;486:215–1

  6. Tisza MJ, Buck CB. A catalog of tens of thousands of viruses from human metagenomes reveals hidden associations with chronic diseases. Proc Natl Acad Sci USA. 2021;118:e2023202118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sartor RB, Wu GD. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology. 2017;152:327–39, e324.

    Article  CAS  Google Scholar 

  8. Becker C, Neurath MF, Wirtz S. The intestinal microbiota in inflammatory bowel disease. ILAR J. 2015;56:192–204.

    Article  CAS  PubMed  Google Scholar 

  9. Imai T, Inoue R, Kawada Y, et al. Characterization of fungal dysbiosis in Japanese patients with inflammatory bowel disease. J Gastroenterol. 2019;54:149–59.

    Article  CAS  PubMed  Google Scholar 

  10. Sokol H, Leducq V, Aschard H, et al. Fungal microbiota dysbiosis in IBD. Gut. 2017;66:1039–48.

    Article  CAS  PubMed  Google Scholar 

  11. Norman JM, Handley SA, Virgin HW. Kingdom-agnostic metagenomics and the importance of complete characterization of enteric microbial communities. Gastroenterology. 2014;146:1459–69.

    Article  CAS  PubMed  Google Scholar 

  12. Norman JM, Handley SA, Baldridge MT, et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell. 2015;160:447–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Maronek M, Link R, Ambro L, et al. Phages and their role in gastrointestinal disease: focus on inflammatory bowel disease. Cells. 2020;9:1013.

    Article  CAS  PubMed Central  Google Scholar 

  14. Ungaro F, Massimino L, D’Alessio S, et al. The gut virome in inflammatory bowel disease pathogenesis: from metagenomics to novel therapeutic approaches. United Eur Gastroenterol J. 2019;7:999–1007.

    Article  CAS  Google Scholar 

  15. Minot S, Bryson A, Chehoud C, et al. Rapid evolution of the human gut virome. Proc Natl Acad Sci USA. 2013;110:12450–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Beller L, Matthijnssens J. What is (not) known about the dynamics of the human gut virome in health and disease. Curr Opin Virol. 2019;37:52–7.

    Article  PubMed  Google Scholar 

  17. Waller AS, Yamada T, Kristensen DM, et al. Classification and quantification of bacteriophage taxa in human gut metagenomes. ISME J. 2014;8:1391–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Perez-Brocal V, Garcia-Lopez R, Nos P, et al. Metagenomic analysis of Crohn’s disease patients identifies changes in the virome and microbiome related to disease status and therapy, and detects potential interactions and biomarkers. Inflamm Bowel Dis. 2015;21:2515–32.

    Article  PubMed  Google Scholar 

  19. Zuo T, Lu XJ, Zhang Y, et al. Gut mucosal virome alterations in ulcerative colitis. Gut. 2019;68:1169–79.

    Article  CAS  PubMed  Google Scholar 

  20. Nishijima S, Suda W, Oshima K, et al. The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res. 2016;23:125–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Best WR, Becktel JM, Singleton JW, et al. Development of a Crohn’s disease activity index. Nat Cooperative Crohn’s Dis Study Gastroenterol. 1976;70:439–44.

    CAS  Google Scholar 

  22. Imaeda H, Bamba S, Takahashi K, et al. Relationship between serum infliximab trough levels and endoscopic activities in patients with Crohn’s disease under scheduled maintenance treatment. J Gastroenterol. 2014;49:674–82.

    Article  PubMed  Google Scholar 

  23. Hirayama H, Morita Y, Imai T, et al. Ustekinumab trough levels predicting laboratory and endoscopic remission in patients with Crohn’s disease. BMC Gastroenterol. 2022;22:195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rutgeerts P, Geboes K, Vantrappen G, et al. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99:956–63.

    Article  CAS  PubMed  Google Scholar 

  25. Matsumoto M, Inoue R, Tsuruta T, et al. Long-term oral administration of cows’ milk improves insulin sensitivity in rats fed a high-sucrose diet. Br J Nutr. 2009;102:1324–33.

    Article  CAS  PubMed  Google Scholar 

  26. Inoue R, Sakaue Y, Sawai C, et al. A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders. Biosci Biotechnol Biochem. 2016;80:2450–8.

    Article  CAS  PubMed  Google Scholar 

  27. Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37:852–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Callahan BJ, McMurdie PJ, Rosen MJ, et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wood DE, Lu J, Langmead B. Improved metagenomic analysis with Kraken 2. Genome Biol. 2019;20:257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE. 2013;8:e61217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Parks DH, Tyson GW, Hugenholtz P, et al. STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics. 2014;30:3123–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Nishino K, Nishida A, Inoue R, et al. Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease. J Gastroenterol. 2018;53:95–106.

    Article  PubMed  Google Scholar 

  34. Kauffman KM, Hussain FA, Yang J, et al. A major lineage of non-tailed dsDNA viruses as unrecognized killers of marine bacteria. Nature. 2018;554:118–22.

    Article  CAS  PubMed  Google Scholar 

  35. Chen YR, Zheng HM, Zhang GX, et al. High Oscillospira abundance indicates constipation and low BMI in the Guangdong Gut Microbiome Project. Sci Rep. 2020;10:9364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gophna U, Konikoff T, Nielsen HB. Oscillospira and related bacteria—from metagenomic species to metabolic features. Environ Microbiol. 2017;19:835–41.

    Article  CAS  PubMed  Google Scholar 

  37. Anand S, Kaur H, Mande SS. Comparative in silico analysis of butyrate production pathways in gut commensals and pathogens. Front Microbiol. 2016;7:1945.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Clooney AG, Sutton TDS, Shkoporov AN, et al. Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease. Cell Host Microbe. 2019;26:764–78, e765.

    Article  CAS  Google Scholar 

  39. Pascal V, Pozuelo M, Borruel N, et al. A microbial signature for Crohn’s disease. Gut. 2017;66:813–22.

    Article  CAS  PubMed  Google Scholar 

  40. Liang G, Conrad MA, Kelsen JR, et al. Dynamics of the stool virome in very early-onset inflammatory bowel disease. J Crohns Colitis. 2020;14:1600–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dutilh BE, Cassman N, McNair K, et al. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nat Commun. 2014;5:4498.

    Article  CAS  PubMed  Google Scholar 

  42. Brown BP, Chopera D, Havyarimana E, et al. crAssphage genomes identified in fecal samples of an adult and infants with evidence of positive genomic selective pressure within tail protein genes. Virus Res. 2021;292:198219.

    Article  CAS  PubMed  Google Scholar 

  43. Guerin E, Shkoporov A, Stockdale SR, et al. Biology and taxonomy of crAss-like bacteriophages, the most abundant virus in the human gut. Cell Host Microbe. 2018;24:653–64, e656.

    Article  CAS  Google Scholar 

  44. Honap TP, Sankaranarayanan K, Schnorr SL, et al. Biogeographic study of human gut-associated crAssphage suggests impacts from industrialization and recent expansion. PLoS ONE. 2020;15:e0226930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yang K, Niu J, Zuo T, et al. Alterations in the gut virome in obesity and type 2 diabetes mellitus. Gastroenterology. 2021;161:1257–69, 1213.

    Article  CAS  Google Scholar 

  46. Gogokhia L, Buhrke K, Bell R, et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe. 2019;25:285–99, e288.

    Article  CAS  Google Scholar 

  47. Wang W, Jovel J, Halloran B, et al. Metagenomic analysis of microbiome in colon tissue from subjects with inflammatory bowel diseases reveals interplay of viruses and bacteria. Inflamm Bowel Dis. 2015;21:1419–27.

    PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Number JP20gm1010008h9904 (AA), and in part by a Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan under grant number 22K07664 and 22K08054 (AA), and in part by a Health and Labour Sciences Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan under Grant Number 20FC1037 (AA).

Author information

Authors and Affiliations

  1. Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan

    Takayuki Imai, Atsushi Nishida, Yoshihiro Yokota, Masahiro Kawahara & Akira Andoh

  2. Department of Applied Biological Science, Faculty of Agriculture, Setsunan University, Hirakata, Osaka, 573-0101, Japan

    Ryo Inoue & So Morishima

  3. Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, 305-8566, Japan

    Hiroyuki Kusada & Hideyuki Tamaki

Authors
  1. Takayuki Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryo Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atsushi Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshihiro Yokota
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. So Morishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masahiro Kawahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroyuki Kusada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hideyuki Tamaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akira Andoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akira Andoh.

Ethics declarations

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 51 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Imai, T., Inoue, R., Nishida, A. et al. Features of the gut prokaryotic virome of Japanese patients with Crohn’s disease. J Gastroenterol 57, 559–570 (2022). https://doi.org/10.1007/s00535-022-01882-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-022-01882-8

Keywords

Search

Navigation