Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2018

Open Access 01-12-2018 | Research article

Age and fecal microbial strain-specific differences in patients with spondyloarthritis

Authors: Matthew L. Stoll, Pamela F. Weiss, Jennifer E. Weiss, Peter A. Nigrovic, Barbara S. Edelheit, S. Lou Bridges Jr, Maria I. Danila, Charles H. Spencer, Marilynn G. Punaro, Kenneth Schikler, Andreas Reiff, Ranjit Kumar, Randy Q. Cron, Casey D. Morrow, Elliot J. Lefkowitz

Published in: Arthritis Research & Therapy | Issue 1/2018

Login to get access

Abstract

Background

Prior studies have demonstrated abnormalities in the composition of the gastrointestinal microbiota in pediatric and adult patients with spondyloarthritis (SpA). In particular, diminished fecal abundance of Faecalibacterium prausnitzii and abnormalities in both directions in the abundance of the Bacteroides genus have been identified.

Methods

We obtained fecal specimens from 30 children with treatment-naïve enthesitis-related arthritis (ERA) and 19 healthy controls, as well as specimens from 11 adult patients with longstanding SpA and 10 adult healthy controls. All of the samples underwent sequencing of the 16S ribosomal DNA. A subset of the pediatric fecal samples was subjected to shotgun metagenomics sequencing.

Results

ERA patients had decreased abundance of the anti-inflammatory F. prausnitzii A2-165 strain (41 ± 28% versus 54 ± 20% of all sequences matching F. prausnitzii, p = 0.084) and an increased abundance of the control F. prausnitzii L2/6 strain (28 ± 28% versus 15 ± 15%, p = 0.038). Similar trends were observed in adults with longstanding SpA (n = 11) and controls (n = 10). In contrast, the fecal abundance of Bacteroides fragilis was increased in ERA subjects (2.0 ± 4.0% versus 0.45 ± 0.7% of all sequences, p = 0.045), yet was diminished in adult subjects (0.2 ± % versus 1.0 ± % of all sequences, p = 0.106). Shotgun metagenomics sequencing of the fecal DNA in the pediatric subjects revealed diminished coverage of the butanoate pathway (abundance normalized to controls of 1 ± 0.48 versus 0.72 ± 0.33 in ERA, p = 0.037).

Conclusions

The anti-inflammatory F. prausnitzii A2-165 strain appears to be depleted in both pediatric and adult SpA. In contrast, B. fragilis may be depleted in adult disease yet abundant in pediatric SpA, suggesting developmental effects on the immune system.
Appendix
Available only for authorised users
Literature
1.
2.
Sheehan D, Shanahan F. The gut microbiota in inflammatory bowel disease. Gastroenterol Clin North Am. 2017;46(1):143–54.CrossRefPubMed
3.
Hansen JJ, Sartor RB. Therapeutic manipulation of the microbiome in IBD: current results and future approaches. Curr Treat Options Gastroenterol. 2015;13(1):105–20.CrossRefPubMedPubMedCentral
4.
van Sommeren S, Janse M, Karjalainen J, Fehrmann R, Franke L, Fu J, et al. Extraintestinal manifestations and complications in inflammatory bowel disease: from shared genetics to shared biological pathways. Inflamm Bowel Dis. 2014;20(6):987–94.PubMed
5.
Stebbings S, Munro K, Simon MA, Tannock G, Highton J, Harmsen H, et al. Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis. Rheumatology (Oxford). 2002;41(12):1395–401.CrossRef
6.
Tito RY, Cypers H, Joossens M, Varkas G, Van Praet L, Glorieus E, et al. Brief Report: Dialister as a microbial marker of disease activity in spondyloarthritis. Arthritis Rheumatol. 2017;69(1):114–21.CrossRefPubMed
7.
Aggarwal A, Sarangi AN, Gaur P, Shukla A, Aggarwal R. Gut microbiome in children with enthesitis-related arthritis in a developing country and the effect of probiotic administration. Clin Exp Immunol. 2017;187(3):480–9.CrossRefPubMed
8.
Stoll ML, Kumar R, Morrow CD, Lefkowitz EJ, Cui X, Genin A, et al. Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther. 2014;16(6):486.CrossRefPubMedPubMedCentral
9.
Cao Y, Shen J, Ran ZH. Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Gastroenterol Res Pract. 2014;2014:872725.PubMedPubMedCentral
10.
Hold GL, Schwiertz A, Aminov RI, Blaut M, Flint HJ. Oligonucleotide probes that detect quantitatively significant groups of butyrate-producing bacteria in human feces. Appl Environ Microbiol. 2003;69(7):4320–4.CrossRefPubMedPubMedCentral
11.
Stoll ML, Kumar R, Lefkowitz EJ, Cron RQ, Morrow CD, Barnes S. Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors. Genes Immun. 2016;17(7):400–5.CrossRefPubMedPubMedCentral
12.
Muller PH, De Meij TG, Westedt M, De Groot EF, Allaart CF, Brinkman DM, et al. Disturbance of microbial core species in new-onset juvenile idiopathic arthritis. J Pediatr Infect Dis. 2017;12:131–5.CrossRef
13.
Tejesvi MV, Arvonen M, Kangas SM, Keskitalo PL, Pirttila AM, Karttunen TJ, et al. Faecal microbiome in new-onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis. 2016;35(3):363–70.CrossRefPubMed
14.
Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2:e01202.CrossRefPubMedPubMedCentral
15.
Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol. 2016;68(11):2646–661.
16.
Martin R, Miquel S, Benevides L, Bridonneau C, Robert V, Hudault S, et al. Functional characterization of novel Faecalibacterium prausnitzii strains isolated from healthy volunteers: a step forward in the use of F prausnitzii as a next-generation probiotic. Front Microbiol. 2017;8:1226.CrossRefPubMedPubMedCentral
17.
18.
De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107(33):14691–6.CrossRefPubMedPubMedCentral
19.
Zhang J, Guo Z, Xue Z, Sun Z, Zhang M, Wang L, et al. A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities. ISME J. 2015;9(9):1979–90.CrossRefPubMedPubMedCentral
20.
Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.PubMed
21.
Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777–83.CrossRefPubMed
22.
Rudwaleit M, van der Heijde D, Landewe R, Akkoc N, Brandt J, Chou CT, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis. 2011;70(1):25–31.CrossRefPubMed
23.
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665–73.CrossRefPubMed
24.
Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–3.CrossRefPubMedPubMedCentral
25.
26.
Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335–6.CrossRefPubMedPubMedCentral
27.
Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol. 2009;75(23):7537–41.CrossRefPubMedPubMedCentral
28.
Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73(16):5261–7.CrossRefPubMedPubMedCentral
29.
DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. 2006;72(7):5069–72.CrossRefPubMedPubMedCentral
30.
31.
32.
Abubucker S, Segata N, Goll J, Schubert AM, Izard J, Cantarel BL, et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput Biol. 2012;8(6):e1002358.CrossRefPubMedPubMedCentral
33.
Pundir S, Martin MJ, O'Donovan C. UniProt Protein Knowledgebase. Methods Mol Biol. 2017;1558:41–55.CrossRefPubMed
34.
Buchfink B, Xie C, Huson DH. Fast and sensitive protein alignment using DIAMOND. Nat Methods. 2015;12(1):59–60.CrossRefPubMed
35.
Caspi R, Altman T, Billington R, Dreher K, Foerster H, Fulcher CA, et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. Nucleic Acids Res. 2014;42(Database issue):D459–71.CrossRefPubMed
36.
Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 2016;44(D1):D457–62.CrossRefPubMed
37.
Kelly BJ, Gross R, Bittinger K, Sherrill-Mix S, Lewis JD, Collman RG, et al. Power and sample-size estimation for microbiome studies using pairwise distances and PERMANOVA. Bioinformatics. 2015;31(15):2461–8.CrossRefPubMedPubMedCentral
38.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful appraoch to multiple testing. J R Stat Soc B. 1995;57:289–300.
39.
Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105(43):16731–6.CrossRefPubMedPubMedCentral
40.
Rossi O, van Berkel LA, Chain F, Tanweer Khan M, Taverne N, Sokol H, et al. Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses. Sci Rep. 2016;6:18507.CrossRefPubMedPubMedCentral
41.
Song H, Yoo Y, Hwang J, Na YC, Kim HS. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol. 2016;137(3):852–60.CrossRefPubMed
42.
Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011;332(6032):974–7.CrossRefPubMedPubMedCentral
43.
Costello ME, Ciccia F, Willner D, Warrington N, Robinson PC, Gardiner B, et al. Intestinal dysbiosis in ankylosing spondylitis. Arthritis Rheumatol. 2015;67:686–91.CrossRefPubMed
44.
Breban M, Tap J, Leboime A, Said-Nahal R, Langella P, Chiocchia G, et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann Rheum Dis. 2017;76(9):1614–622.
45.
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–4.CrossRefPubMed
46.
Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008;27(2):104–19.CrossRefPubMed
47.
Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 1994;180(6):2359–64.CrossRefPubMed
48.
Segain JP, Raingeard De La Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, et al. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut. 2000;47(3):397–403.CrossRefPubMedPubMedCentral
49.
Vaahtovuo J, Munukka E, Korkeamaki M, Luukkainen R, Toivanen P. Fecal microbiota in early rheumatoid arthritis. J Rheumatol. 2008;35(8):1500–5.PubMed
50.
Vatanen T, Kostic AD, d'Hennezel E, Siljander H, Franzosa EA, Yassour M, et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell. 2016;165(4):842–53.CrossRefPubMedPubMedCentral
51.
52.
Lin P, Bach M, Asquith M, Lee AY, Akileswaran L, Stauffer P, et al. HLA-B27 and human beta2-microglobulin affect the gut microbiota of transgenic rats. PLoS One. 2014;9(8):e105684.CrossRefPubMedPubMedCentral
53.
Mielants H, De Keyser F, Baeten D, Van den Bosch F. Gut inflammation in the spondyloarthropathies. Curr Rheumatol Rep. 2005;7(3):188–94.CrossRefPubMed
54.
Arvonen M, Virta LJ, Pokka T, Kroger L, Vahasalo P. Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections? J Rheumatol. 2015;42(3):521–6.CrossRefPubMed
55.
Horton DB, Scott FI, Haynes K, Putt ME, Rose CD, Lewis JD, et al. Antibiotic exposure and juvenile idiopathic arthritis: a case-control study. Pediatrics. 2015;136(2):e333–43.CrossRefPubMedPubMedCentral
Metadata
Title
Age and fecal microbial strain-specific differences in patients with spondyloarthritis
Authors
Matthew L. Stoll
Pamela F. Weiss
Jennifer E. Weiss
Peter A. Nigrovic
Barbara S. Edelheit
S. Lou Bridges Jr
Maria I. Danila
Charles H. Spencer
Marilynn G. Punaro
Kenneth Schikler
Andreas Reiff
Ranjit Kumar
Randy Q. Cron
Casey D. Morrow
Elliot J. Lefkowitz
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2018
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-018-1510-6

Other articles of this Issue 1/2018

Arthritis Research & Therapy 1/2018 Go to the issue

Research article

Association between general joint hypermobility and knee, hip, and lumbar spine osteoarthritis by race: a cross-sectional study

Research article

Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibroblasts and proliferation: a new potential target for antifibrotic therapy

Research article

Extravascular manifestations of Takayasu arteritis: focusing on the features shared with spondyloarthritis

Research article

Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3)

Commentary

Rheumatology in East Asia

Research article

Metabolomics approach by 1H NMR spectroscopy of serum reveals progression axes for asymptomatic hyperuricemia and gout

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits