1887

Journal of Medical Microbiology logo

Volume 69, Issue 6

Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment Open Access

Abstract

. Ankylosing spondylitis (AS) is a systemic progressive disease with an unknown etiology that may be related to the gut microbiome. Therefore, a more thorough understanding of its pathogenesis is necessary for directing future therapy.

. We aimed to determine the differences in intestinal microbial composition between healthy individuals and patients with AS who received and who did not receive treatment interventions. In parallel, the pathology of AS in each patient was analysed to better understand the link between AS treatment and the intestinal microbiota of the patients.

. Sixty-six faecal DNA samples, including 37 from healthy controls (HCs), 11 from patients with untreated AS (NM), 7 from patients treated with nonsteroidal anti-inflammatory drugs (e.g. celecoxib; WM) and 11 from patients treated with Chinese herbal medicine (CHM), such as the Bushen–Qiangdu–Zhilv decoction, were collected and used in the drug effect analysis. All samples were sequenced using Illumina HiSeq 4000 and the microbial composition was determined.

. Four species were enriched in the patients with AS: , , and (HC vs. NM, <0.05); only was found to be significantly changed in the NM-HC comparison. No additional species were found in the HC vs. CHM analysis, which indicated a beneficial effect of CHM in removing the other three strains. was found to be significantly increased in the comparison between the HC and WM groups, along with four other species (, Clostridiales bacterium 1_7_47FAA, and ). The patients with AS harboured more bacterial species associated with carbohydrate metabolism and glycan biosynthesis in their faeces. They also had bacterial profiles less able to biodegrade xenobiotics or synthesize and transport vitamins.

. The gut microbiota of the patients with AS varied from that of the HCs, and the treatment had an impact on this divergence. Our data provide insight that could guide improvements in AS treatment.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Ankylosing spondylitis , Drug effect , Flavonifractor plautii , Heparan sulfate degradation and Pathogenesis
Funding
This study was supported by the:
  • Zhejiang Traditional Chinese Medicine Administration (Award No.YN2015MJ06, No.YN2018ML08, No.YN2018ZD06)
    • Principle Award Recipient: Not Applicable
  • Guangzhou Science, Technology and Innovation Commission (CN) (Award No.201710010076)
    • Principle Award Recipient: Not Applicable
  • the Key Research Project of Guangzhou University of Chinese Medicine (Award No.XK2019021)
    • Principle Award Recipient: Not Applicable
  • Water Resources Department of Guangdong Province (CN) (Award No.2016A020226041)
    • Principle Award Recipient: Not Applicable
  • National Natural Science Foundation of China (Award No. 81673898)
    • Principle Award Recipient: Not Applicable
© 2020 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001107
2019-11-28
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jmm/69/6/797.html?itemId=/content/journal/jmm/10.1099/jmm.0.001107&mimeType=html&fmt=ahah

References

  1. Costello ME, Elewaut D, Kenna TJ, Brown MA, Microbes BMA. Microbes, the gut and ankylosing spondylitis. Arthritis Res Ther 2013; 15:214 [View Article][PubMed]
     [Google Scholar]
  2. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis--insights into pathogenesis. Nat Rev Rheumatol 2016; 12:81–91 [View Article][PubMed]
     [Google Scholar]
  3. Kiltz U, Baraliakos X, Karakostas P, Igelmann M, Kalthoff L et al. The degree of spinal inflammation is similar in patients with axial spondyloarthritis who report high or low levels of disease activity: a cohort study. Ann Rheum Dis 2012; 71:1207–1211 [View Article][PubMed]
     [Google Scholar]
  4. Braun J, Sieper J. Ankylosing spondylitis. The Lancet 2007; 369:1379–1390 [View Article]
     [Google Scholar]
  5. Evans DM, Spencer CCA, Pointon JJ, Su Z, Harvey D et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet 2011; 43:761–767 [View Article]
     [Google Scholar]
  6. Tsui F, Tsui HW, Akram A, Haroon N, Inman R. The genetic basis of ankylosing spondylitis: new insights into disease pathogenesis. Appl Clin Genet 2014; 7:105–115 [View Article]
     [Google Scholar]
  7. Rosenbaum JT, Lin P, Asquith M, Costello M-E, Kenna TJ et al. Does the microbiome play a causal role in spondyloarthritis?. Clin Rheumatol 2014; 33:763–767 [View Article]
     [Google Scholar]
  8. Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2M: an animal model of HLA-B27-associated human disorders. Cell 1990; 63:1099–1112 [View Article][PubMed]
     [Google Scholar]
  9. Yang L, Wang L, Wang X, Xian C, Lu H. A possible role of intestinal microbiota in the pathogenesis of ankylosing spondylitis. Int J Mol Sci 2016; 17:2126 [View Article]
     [Google Scholar]
  10. Rashid T, Ebringer A. Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry. Autoimmune Dis 2012; 2012:539282 [View Article][PubMed]
     [Google Scholar]
  11. Wen C, Zheng Z, Shao T, Liu L, Xie Z et al. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol 2017; 18:142 [View Article]
     [Google Scholar]
  12. Lubrano E, Spadaro A, Amato G, Benucci M, Cavazzana I et al. Tumour necrosis factor alpha inhibitor therapy and rehabilitation for the treatment of ankylosing spondylitis: a systematic review. Semin Arthritis Rheum 2015; 44:542–550 [View Article]
     [Google Scholar]
  13. Goei The HS, Steven MM, van der Linden SM, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a comparison of the Rome, New York and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Rheumatology 1985; 24:242–249 [View Article]
     [Google Scholar]
  14. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P et al. A new approach to defining disease status in ankylosing spondylitis: the Bath ankylosing spondylitis disease activity index. J Rheumatol 1994; 21:2286–2291[PubMed]
     [Google Scholar]
  15. Qin J, Li Y, Cai Z, Li S, Zhu J et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490:55–60 [View Article]
     [Google Scholar]
  16. Chen Y, Chen Y, Shi C, Huang Z, Zhang Y et al. SOAPnuke: a MapReduce acceleration-supported software for integrated quality control and preprocessing of high-throughput sequencing data. Gigascience 2018; 7:1–6 [View Article]
     [Google Scholar]
  17. Li R, Yu C, Li Y, Lam TW, Yiu SM et al. SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 2009; 25:1966–1967 [View Article][PubMed]
     [Google Scholar]
  18. Nielsen HB, Almeida M, Juncker AS, Rasmussen S, Li J et al. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol 2014; 32:822–828 [View Article]
     [Google Scholar]
  19. Xie H, Guo R, Zhong H, Feng Q, Lan Z et al. Shotgun Metagenomics of 250 adult twins reveals genetic and environmental impacts on the gut microbiome. Cell Systems 2016; 3:572–584 [View Article]
     [Google Scholar]
  20. Segata N, Waldron L, Ballarini A, Narasimhan V, Jousson O et al. Metagenomic microbial community profiling using unique clade-specific marker genes. Nat Methods 2012; 9:811–814 [View Article]
     [Google Scholar]
  21. Short DF, Zemel BS, Gilsanz V, Kalkwarf HJ, Lappe JM et al. Fitting of bone mineral density with consideration of anthropometric parameters. Osteoporos Int 2011; 22:1047–1057 [View Article][PubMed]
     [Google Scholar]
  22. Patil KR, Nielsen J. Uncovering transcriptional regulation of metabolism by using metabolic network topology. Proc Natl Acad Sci USA 2005; 102:2685–2689 [View Article][PubMed]
     [Google Scholar]
  23. Robin X, Turck N, Hainard A, Tiberti N, Lisacek F et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 2011; 12:77 [View Article]
     [Google Scholar]
  24. Truong DT, Franzosa EA, Tickle TL, Scholz M, Weingart G et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat Methods 2015; 12:902–903 [View Article]
     [Google Scholar]
  25. Bao X, Moseman EA, Saito H, Petryanik B, Thiriot A et al. Endothelial heparan sulfate controls chemokine presentation in recruitment of lymphocytes and dendritic cells to lymph nodes. Immunity 2010; 33:817–829 [View Article]
     [Google Scholar]
  26. Defois C, Ratel J, Garrait G, Denis S, Le Goff O et al. Food chemicals disrupt human gut microbiota activity and impact intestinal homeostasis as revealed by in vitro systems. Sci Rep 2018; 8:11006 [View Article]
     [Google Scholar]
  27. Palmer D, El Miedany Y. Tackling comorbidity associated with rheumatic diseases in standard practice. Br J Nurs 2017; 26:380–387 [View Article][PubMed]
     [Google Scholar]
  28. Shipton MJ, Thachil J. Vitamin B12 deficiency – A 21st century perspective. Clin Med 2015; 15:145–150 [View Article][PubMed]
     [Google Scholar]
  29. Dai Z, Koh W-P. B-Vitamins and bone Health–A review of the current evidence. Nutrients 2015; 7:3322–3346 [View Article]
     [Google Scholar]
  30. Faith JJ, Ahern PP, Ridaura VK, Cheng J, Gordon JI. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci Transl Med 2014; 6:220ra11 [View Article]
     [Google Scholar]
  31. Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR et al. The role of short-chain fatty acids in health and disease. Adv Immunol 2014; 121:91–119 [View Article][PubMed]
     [Google Scholar]
  32. Pequegnat B, Sagermann M, Valliani M, Toh M, Chow H et al. A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium. Vaccine 2013; 31:2787–2790 [View Article]
     [Google Scholar]
  33. Dehoux P, Marvaud JC, Abouelleil A, Earl AM, Lambert T et al. Comparative genomics of Clostridium bolteae and Clostridium clostridioforme reveals species-specific genomic properties and numerous putative antibiotic resistance determinants. BMC Genomics 2016; 17:819 [View Article]
     [Google Scholar]
  34. Thomson P, Medina DA, Ortúzar V, Gotteland M, Garrido D. Anti-Inflammatory effect of microbial consortia during the utilization of dietary polysaccharides. Food Res Int 2018; 109:14–23 [View Article][PubMed]
     [Google Scholar]
  35. Zhang X, Osaka T, Tsuneda S. Bacterial metabolites directly modulate farnesoid X receptor activity. Nutr Metab 2015; 12:48 [View Article]
     [Google Scholar]
  36. Mohan R, Namsolleck P, Lawson PA, Osterhoff M, Collins MD et al. Clostridium asparagiforme sp. nov., isolated from a human faecal sample. Syst Appl Microbiol 2006; 29:292–299 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001107
Loading
Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment
J. Med. Microbiol. 69, 797 (2020); https://doi.org/10.1099/jmm.0.001107
/content/journal/jmm/10.1099/jmm.0.001107
/content/journal/jmm/10.1099/jmm.0.001107
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error