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

doi:10.1186/s13075-018-1510-6

. 2018 Jan 30;20(1):14.

doi: 10.1186/s13075-018-1510-6.

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

Affiliations

¹ University of Alabama at Birmingham, Birmingham, AL, USA. mstoll@peds.uab.edu.
² Children's Hospital of Philadelphia, Philadelphia, PA, USA.
³ Hackensack University Medical Center, Hackensack, NJ, USA.
⁴ Boston Children's Hospital and Brigham and Women's Hospital, Boston, MA, USA.
⁵ Connecticut Children's Medical Center, Hartford, CT, USA.
⁶ University of Alabama at Birmingham, Birmingham, AL, USA.
⁷ Nationwide Children's Hospital, Columbus, OH, USA.
⁸ Texas Scottish Rite Hospital, Dallas, TX, USA.
⁹ University of Louisville, Louisville, KY, USA.
¹⁰ Children's Hospital of Los Angeles, Los Angeles, CA, USA.

PMID: 29382366
PMCID: PMC5791354
DOI: 10.1186/s13075-018-1510-6

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

Matthew L Stoll et al. Arthritis Res Ther. 2018.

. 2018 Jan 30;20(1):14.

doi: 10.1186/s13075-018-1510-6.

Authors

Affiliations

¹ University of Alabama at Birmingham, Birmingham, AL, USA. mstoll@peds.uab.edu.
² Children's Hospital of Philadelphia, Philadelphia, PA, USA.
³ Hackensack University Medical Center, Hackensack, NJ, USA.
⁴ Boston Children's Hospital and Brigham and Women's Hospital, Boston, MA, USA.
⁵ Connecticut Children's Medical Center, Hartford, CT, USA.
⁶ University of Alabama at Birmingham, Birmingham, AL, USA.
⁷ Nationwide Children's Hospital, Columbus, OH, USA.
⁸ Texas Scottish Rite Hospital, Dallas, TX, USA.
⁹ University of Louisville, Louisville, KY, USA.
¹⁰ Children's Hospital of Los Angeles, Los Angeles, CA, USA.

PMID: 29382366
PMCID: PMC5791354
DOI: 10.1186/s13075-018-1510-6

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.

Keywords: Bacteroides; Faecalibacterium; Microbiota; Sequencing; Spondyloarthritis.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Office of the IRB at UAB as well as at the respective study sites: Children’s Hospital of Philadelphia, Hackensack University Medical Center, Children’s Hospital Boston, Connecticut Children’s Medical Center, Nationwide Children’s Hospital, University of Texas at Southwestern Medical Center (which governs Texas Scottish Rite Hospital), University of Louisville, and Children’s Hospital of LA. Informed consent and assent as appropriate were obtained from all study subjects and/or their guardians as per local regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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

Figures

**Fig. 1**
Principal coordinates analysis of the 16S sequencing results obtained from children with ERA and pediatric healthy controls demonstrating clustering by diagnosis. Blue and red dots reflect ERA patients and controls, respectively

**Fig. 2**
Strain-level variation in the fecal abundance of *Faecalibacterium prausnitzii* in children with ERA and pediatric controls. Abundance of *F. prausnitzii* as a percentage of total fecal content is similar in patients and controls (a). As a percentage of total *F. prausnitzii*, children with ERA have a trend toward decreased fecal abundance of the anti-inflammatory A2-165 strain (b) as well as increased abundance of the L2/6 strain (c). ERA enthesitis-related arthritis

**Fig. 3**
Fecal abundance of *Bacteroides fragilis* in pediatric and adult subjects with SpA. Increased fecal abundance is observed in ERA patients compared to pediatric controls (a), while a trend toward decreased fecal abundance was observed in adult SpA patients compared to adult controls (b). ERA enthesitis-related arthritis, SpA spondyloarthritis

**Fig. 4**
Fecal abundance of bacterial genes comprising a pathway involved in butyrate synthesis. Results of two separate studies shown. For each, each subject was normalized to the mean of the healthy controls for that study, and the combined results are shown. ERA enthesitis-related arthritis

See this image and copyright information in PMC

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References

1. Stoll ML. Gut microbes, immunity, and spondyloarthritis. Clin Immunol. 2015;159(2):134–42. doi: 10.1016/j.clim.2015.05.001. - DOI - PubMed
1. Sheehan D, Shanahan F. The gut microbiota in inflammatory bowel disease. Gastroenterol Clin North Am. 2017;46(1):143–54. doi: 10.1016/j.gtc.2016.09.011. - DOI - PubMed
1. 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. doi: 10.1007/s11938-014-0042-7. - DOI - PMC - PubMed
1. 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
1. 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. doi: 10.1093/rheumatology/41.12.1395. - DOI - PubMed

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[1] Stoll ML. Gut microbes, immunity, and spondyloarthritis. Clin Immunol. 2015;159(2):134–42. doi: 10.1016/j.clim.2015.05.001. - DOI - PubMed

[2] Stoll ML. Gut microbes, immunity, and spondyloarthritis. Clin Immunol. 2015;159(2):134–42. doi: 10.1016/j.clim.2015.05.001. - DOI - PubMed

[3] Sheehan D, Shanahan F. The gut microbiota in inflammatory bowel disease. Gastroenterol Clin North Am. 2017;46(1):143–54. doi: 10.1016/j.gtc.2016.09.011. - DOI - PubMed

[4] Sheehan D, Shanahan F. The gut microbiota in inflammatory bowel disease. Gastroenterol Clin North Am. 2017;46(1):143–54. doi: 10.1016/j.gtc.2016.09.011. - DOI - PubMed

[5] 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. doi: 10.1007/s11938-014-0042-7. - DOI - PMC - PubMed

[6] 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. doi: 10.1007/s11938-014-0042-7. - DOI - PMC - PubMed

[7] 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

[8] 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

[9] 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. doi: 10.1093/rheumatology/41.12.1395. - DOI - PubMed

[10] 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. doi: 10.1093/rheumatology/41.12.1395. - DOI - PubMed

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