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Published in: Clinical Rheumatology 9/2020

01-09-2020 | Ankylosing Spondylitis | Original Article

Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis

Authors: Fangze Zhang, Cuili Ma, Bin Zhang, Liqi Bi

Published in: Clinical Rheumatology | Issue 9/2020

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Abstract

Objectives

This study aimed to investigate the relationship among smoking, TNF-α-blocker therapy, and the dynamic changes in gut microbiota in patients with ankylosing spondylitis (AS).

Methods

Using a 16S rRNA sequence, 98 fecal samples of 20 AS patients collected after 0, 1, 3 and 6 months of anti-TNF-α treatment and from 20 matched health controls were examined. The variation in composition, abundance, and diversity of gut microbiota was analyzed. The dynamic effects of smoking and treatment on gut microbiota and therapeutic efficacy in AS patients were studied.

Results

The increased relative abundance of microbiota in AS nonsmokers was g_Comamonas and g_Desulfovibrio, while that in AS smokers was g_Actinomyces, g_Collinsella, g_Lachnospiraceae_UCG-008, and g_Paraprevotella. The relative abundance of gut microbiota showed dynamic variation. The improvement rate of ASDAS in AS nonsmokers was higher than that in AS smokers (2.297 vs 1.736) after anti-TNF-α treatment. The β-diversity of gut microbiota in AS smokers was lower than that in AS nonsmokers and improved with treatment.

Conclusions

Both smoking and TNF-α-blocker had significant effects on the composition, relative abundance, and diversity of gut microbiota in AS patients. The AS smokers characteristically shared g_Collinsella and g_Dorea. The relative abundance of gut microbiota revealed high variability and was in dynamic fluctuation during treatment. The response of gut microbiota to anti-TNF-α treatment was found to be heterogeneous and selective. AS nonsmokers showed a greater improvement rate of ASDAS-CRP with treatment than AS smokers did. The AS smokers showed a lower β-diversity of gut microbiota, and improved after treatment.
Key Points
• Characterized the dynamic variation in gut microbiota in AS patients classified as smokers and nonsmokers during treatment with anti-TNF-α.
• Confirmed the interaction between smoking, anti-TNF-α therapy, and gut microbiota.
Literature
6.
go back to reference Martinez A, Pacheco-Tena C, Vazquez-Mellado J, Burgos-Vargas R (2004) Relationship between disease activity and infection in patients with spondyloarthropathies. Ann Rheum Dis 63:1338–1340CrossRefPubMedPubMedCentral Martinez A, Pacheco-Tena C, Vazquez-Mellado J, Burgos-Vargas R (2004) Relationship between disease activity and infection in patients with spondyloarthropathies. Ann Rheum Dis 63:1338–1340CrossRefPubMedPubMedCentral
8.
go back to reference Rath HC, Wilson KH, Sartor RB (1999) Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli. Infect Immun 67:2969–2974CrossRefPubMedPubMedCentral Rath HC, Wilson KH, Sartor RB (1999) Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli. Infect Immun 67:2969–2974CrossRefPubMedPubMedCentral
9.
go back to reference Mäki-Ikola O, Leirisalo-Repo M, Turunen U, Granfors K (1997) Association of gut inflammation with increased serum IgA class Klebsiella antibody concentrations in patients with axial ankylosing spondylitis (AS): implication for different aetiopathogenetic mechanisms for axial and peripheral AS? Ann Rheum Dis 56:180–183CrossRefPubMedPubMedCentral Mäki-Ikola O, Leirisalo-Repo M, Turunen U, Granfors K (1997) Association of gut inflammation with increased serum IgA class Klebsiella antibody concentrations in patients with axial ankylosing spondylitis (AS): implication for different aetiopathogenetic mechanisms for axial and peripheral AS? Ann Rheum Dis 56:180–183CrossRefPubMedPubMedCentral
10.
go back to reference Martínez-González O, Cantero-Hinojosa J, Paule-Sastre P, Gómez-Magán JC, Salvatierra-Ríos D (1994) Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives. Br J Rheumatol 33:644–647CrossRefPubMed Martínez-González O, Cantero-Hinojosa J, Paule-Sastre P, Gómez-Magán JC, Salvatierra-Ríos D (1994) Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives. Br J Rheumatol 33:644–647CrossRefPubMed
11.
go back to reference Fragoulis GE, Siebert S, McInnes IB (2016) Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med 67:337–353CrossRefPubMed Fragoulis GE, Siebert S, McInnes IB (2016) Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med 67:337–353CrossRefPubMed
15.
go back to reference Jones GT, Ratz T, Dean LE, Macfariane GJ, Atzeni F (2017) Disease severity in never smokers, ex-smokers, and current smokers with axial spondyloarthritis: results from the Scotland registry for ankylosing spondylitis. Arthritis Care Res 69:1407–1413. https://doi.org/10.1002/acr.23157CrossRef Jones GT, Ratz T, Dean LE, Macfariane GJ, Atzeni F (2017) Disease severity in never smokers, ex-smokers, and current smokers with axial spondyloarthritis: results from the Scotland registry for ankylosing spondylitis. Arthritis Care Res 69:1407–1413. https://​doi.​org/​10.​1002/​acr.​23157CrossRef
16.
go back to reference Van der LS, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368CrossRef Van der LS, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368CrossRef
17.
go back to reference Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21:2286–2291PubMed Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21:2286–2291PubMed
18.
go back to reference Braun J, Pham T, Sieper J, Davis J, van der Linden S, Dougados M, van der Heijde D, ASAS Working Group (2003) International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 62:817–824CrossRefPubMedPubMedCentral Braun J, Pham T, Sieper J, Davis J, van der Linden S, Dougados M, van der Heijde D, ASAS Working Group (2003) International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 62:817–824CrossRefPubMedPubMedCentral
19.
20.
25.
go back to reference De Vos M, Cuvelier C, Mielants H, Veys E, Barbier F, Elewaut A (1989) Ileocolonoscopy in seronegative spondylarthropathy. Gastroenterology 96:339–344CrossRefPubMed De Vos M, Cuvelier C, Mielants H, Veys E, Barbier F, Elewaut A (1989) Ileocolonoscopy in seronegative spondylarthropathy. Gastroenterology 96:339–344CrossRefPubMed
27.
go back to reference Van Praet L, Jans L, Carron P, Jacques P, Glorieus E, Colman R (2014) Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Ann Rheum Dis 73:1186–1189. https://doi.org/10.1136/annrheumdis-2013-203854 Van Praet L, Jans L, Carron P, Jacques P, Glorieus E, Colman R (2014) Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Ann Rheum Dis 73:1186–1189. https://​doi.​org/​10.​1136/​annrheumdis-2013-203854
28.
go back to reference Orchard TR, Thiyagaraja S, Welsh KI, Wordsworth BP, Hill Gaston JS, Jewell DP (2000) Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 118:274–278CrossRefPubMed Orchard TR, Thiyagaraja S, Welsh KI, Wordsworth BP, Hill Gaston JS, Jewell DP (2000) Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 118:274–278CrossRefPubMed
36.
go back to reference Quévrain E, Maubert MA, Michon C, Chain F, Marquant R, Tailhades J, Miquel S, Carlier L, Bermúdez-Humarán LG, Pigneur B, Lequin O, Kharrat P, Thomas G, Rainteau D, Aubry C, Breyner N, Afonso C, Lavielle S, Grill JP, Chassaing G, Chatel JM, Trugnan G, Xavier R, Langella P, Sokol H, Seksik P (2016) Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease. Gut 65:415–425. https://doi.org/10.1136/gutjnl-2014-307649CrossRefPubMed Quévrain E, Maubert MA, Michon C, Chain F, Marquant R, Tailhades J, Miquel S, Carlier L, Bermúdez-Humarán LG, Pigneur B, Lequin O, Kharrat P, Thomas G, Rainteau D, Aubry C, Breyner N, Afonso C, Lavielle S, Grill JP, Chassaing G, Chatel JM, Trugnan G, Xavier R, Langella P, Sokol H, Seksik P (2016) Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease. Gut 65:415–425. https://​doi.​org/​10.​1136/​gutjnl-2014-307649CrossRefPubMed
38.
go back to reference Wu TR, Lin CS, Chang CJ, Lin TL, Martel J, Ko YF, Ojcius DM, Lu CC, Young JD, Lai HC (2019) Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut 68:248–262. https://doi.org/10.1136/gutjnl-2017-315458 Wu TR, Lin CS, Chang CJ, Lin TL, Martel J, Ko YF, Ojcius DM, Lu CC, Young JD, Lai HC (2019) Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut 68:248–262. https://​doi.​org/​10.​1136/​gutjnl-2017-315458
39.
go back to reference Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, Littmann ER, Ling L, Gobourne AC, Miller LC, Docampo MD, Peled JU, Arpaia N, Cross JR, Peets TK, Lumish MA, Shono Y, Dudakov JA, Poeck H, Hanash AM, Barker JN, Perales MA, Giralt SA, Pamer EG, van den Brink MR (2015) Intestinal Blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant 21(8):1373–1383. https://doi.org/10.1016/j.bbmt.2015.04.016CrossRefPubMedPubMedCentral Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, Littmann ER, Ling L, Gobourne AC, Miller LC, Docampo MD, Peled JU, Arpaia N, Cross JR, Peets TK, Lumish MA, Shono Y, Dudakov JA, Poeck H, Hanash AM, Barker JN, Perales MA, Giralt SA, Pamer EG, van den Brink MR (2015) Intestinal Blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant 21(8):1373–1383. https://​doi.​org/​10.​1016/​j.​bbmt.​2015.​04.​016CrossRefPubMedPubMedCentral
41.
go back to reference Kim D, Hofstaedter CE, Zhao C, Mattei L, Tanes C, Clarke E, Lauder A, Sherrill-Mix S, Chehoud C, Kelsen J, Conrad M, Collman RG, Baldassano R, Bushman FD, Bittinger K (2017) Optimizing methods and dodging pitfalls in microbiome research. Microbiome 5(1):52. https://doi.org/10.1186/s40168-017-0267-5 Kim D, Hofstaedter CE, Zhao C, Mattei L, Tanes C, Clarke E, Lauder A, Sherrill-Mix S, Chehoud C, Kelsen J, Conrad M, Collman RG, Baldassano R, Bushman FD, Bittinger K (2017) Optimizing methods and dodging pitfalls in microbiome research. Microbiome 5(1):52. https://​doi.​org/​10.​1186/​s40168-017-0267-5
Metadata
Title
Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis
Authors
Fangze Zhang
Cuili Ma
Bin Zhang
Liqi Bi
Publication date
01-09-2020
Publisher
Springer International Publishing
Published in
Clinical Rheumatology / Issue 9/2020
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-020-05032-4

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