Skip to main content

Advertisement

Log in

Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic arthritis (JIA) responding to two treatment periods with exclusive enteral nutrition (EEN)

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The microbiome and immune system of the digestive tract are highly important in both health and disease. Exclusive enteral nutrition (EEN) is a common anti-inflammatory treatment in children with Crohn’s disease in the European countries, and the mechanism is most likely linked to changes in the intestinal microbiome. In the present study, EEN was given in two treatment periods several months apart to a patient with very severe, disabling juvenile idiopathic arthritis (JIA), with a remarkable clinical response as the result. The aim of the present study was to study how the EEN treatment influenced the microbiome and metabolome of this patient. Fecal samples from before, during, and between treatments with EEN were studied. The microbiome was analyzed by sequencing of 16S rRNA amplicons using Illumina MiSeq, and the metabolome was analyzed using nuclear magnetic resonance. The microbiome changed markedly from treatment with EEN, with a strong reduction of the Bacteroidetes phylum. Metabolic profiles showed clear differences before, during, and between treatment with EEN, where butyrate, propionate, and acetate followed a cyclic pattern with the lowest levels at the end of each treatment period. This patient with JIA showed remarkable clinical improvement after EEN treatment, and we found corresponding changes in both the fecal microbiome and the metabolome. Further studies are needed to explore the pathophysiological role of the intestinal canal in children with JIA.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Petty RE et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31(2):390–392

    PubMed  Google Scholar 

  2. Stoll ML, Punaro M, Patel AS (2011) Fecal calprotectin in children with the enthesitis-related arthritis subtype of juvenile idiopathic arthritis. J Rheumatol 38(10):2274–2275

    Article  PubMed  PubMed Central  Google Scholar 

  3. Conti F et al (2005) Chronic intestinal inflammation and seronegative spondyloarthropathy in children. Dig Liver Dis 37(10):761–767

    Article  CAS  PubMed  Google Scholar 

  4. Lionetti P et al (2000) Evidence of subclinical intestinal inflammation by 99m technetium leukocyte scintigraphy in patients with HLA-B27 positive juvenile onset active spondyloarthropathy. J Rheumatol 27(6):1538–1541

    CAS  PubMed  Google Scholar 

  5. Arvonen M et al (2012) Altered expression of intestinal human leucocyte antigen D-related and immune signalling molecules in juvenile idiopathic arthritis. Clin Exp Immunol 170(3):266–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Belkaid Y, Hand TW (2014) Role of the microbiota in immunity and inflammation. Cell 157(1):121–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Scher JU et al (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2:e01202

    Article  PubMed  PubMed Central  Google Scholar 

  8. Costello ME et al (2014) Intestinal dysbiosis in ankylosing spondylitis. Arthritis Rheumatol 67(3):686–691

    Article  Google Scholar 

  9. Scher JU et al (2015) Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol 67(1):128–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Stoll ML et al (2014) Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther 16(6):486

    Article  PubMed  PubMed Central  Google Scholar 

  11. Tejesvi MV et al (2015) Faecal microbiome in new-onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis

  12. Gevers D et al (2014) The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15(3):382–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kolho KL et al (2015) Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am J Gastroenterol 110(6):921–930

    Article  PubMed  Google Scholar 

  14. Leach ST, Mitchell HM, Eng WR, Zhang L, Day AS (2008) Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn’s disease. Aliment Pharmacol Ther 28(6):724–733

    Article  CAS  PubMed  Google Scholar 

  15. Zachos M, Tondeur M, Griffiths AM (2007) Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 1:CD000542

    PubMed  Google Scholar 

  16. Tjellstrom B et al (2012) Effect of exclusive enteral nutrition on gut microflora function in children with Crohn’s disease. Scand J Gastroenterol 47(12):1454–1459

    Article  PubMed  Google Scholar 

  17. Gerasimidis K et al (2014) Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn’s disease during enteral nutrition. Inflamm Bowel Dis 20(5):861–871

    Article  PubMed  Google Scholar 

  18. Furusawa Y et al (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504(7480):446–450

    Article  CAS  PubMed  Google Scholar 

  19. Fischer R, Bowness P, Kessler BM (2013) Two birds with one stone: doing metabolomics with your proteomics kit. Proteomics 13(23-24):3371–3386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Puchades-Carrasco L, Palomino-Schatzlein M, Perez-Rambla C, Pineda-Lucena A (2015) Bioinformatics tools for the analysis of NMR metabolomics studies focused on the identification of clinically relevant biomarkers. Brief Bioinform

  21. Berntson L (2014) Anti-inflammatory effect by exclusive enteral nutrition (EEN) in a patient with juvenile idiopathic arthritis (JIA): brief report. Clin Rheumatol 33(8):1173–1175

    Article  PubMed  Google Scholar 

  22. Kampmann C, Dicksved J, Engstrand L, Rautelin H (2015) Composition of human faecal microbiota in resistance to Campylobacter infection. Clin Microbiol Infect 22 (1):61.e61–61.e68

  23. Hugerth LW et al (2014) DegePrime, a program for degenerate primer design for broad-taxonomic-range PCR in microbial ecology studies. Appl Environ Microbiol 80(16):5116–5123

    Article  PubMed  PubMed Central  Google Scholar 

  24. Engstrand Lilja H, Wefer H, Nystrom N, Finkel Y, Engstrand L (2015) Intestinal dysbiosis in children with short bowel syndrome is associated with impaired outcome. Microbiome 3:18

    Article  PubMed  PubMed Central  Google Scholar 

  25. Caporaso JG et al (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26(19):2460–2461

    Article  CAS  PubMed  Google Scholar 

  27. Caporaso JG, Bittinger K, Bushman FD, DeSantis TZ, Andersen GL, Knight R (2010) PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics 26(2):266–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Giongo A et al (2011) Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 5(1):82–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Murri M et al (2013) Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med 11:46

    Article  PubMed  PubMed Central  Google Scholar 

  30. David LA et al (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505(7484):559–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Holmes E, Li JV, Athanasiou T, Ashrafian H, Nicholson JK (2011) Understanding the role of gut microbiome-host metabolic signal disruption in health and disease. Trends Microbiol 19(7):349–359

    Article  CAS  PubMed  Google Scholar 

  32. Madsen RK et al (2011) Diagnostic properties of metabolic perturbations in rheumatoid arthritis. Arthritis Res Ther 13(1):R19

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Department of Women’s and Children’s Health, Uppsala University Hospital, Uppsala, and the Gillbergska Foundation, Uppsala.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lillemor Berntson.

Ethics declarations

The study was approved by the regional ethics committee in Uppsala County (Dnr 2012/378). Oral as well as written consent was obtained from the patient’s parents.

Disclosures

None.

Additional information

Key messages

In this patient with JIA, exclusive enteral nutrition had a remarkable anti-inflammatory effect in two treatment periods, corresponding to changes in fecal microbiota and metabolites.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berntson, L., Agback, P. & Dicksved, J. Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic arthritis (JIA) responding to two treatment periods with exclusive enteral nutrition (EEN). Clin Rheumatol 35, 1501–1506 (2016). https://doi.org/10.1007/s10067-016-3238-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-016-3238-5

Keywords

Navigation