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01-05-2019 | Streptococci | Original Article

Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behcet’s disease (210 characters)

Authors: Jun Shimizu, Takao Kubota, Erika Takada, Kenji Takai, Naruyoshi Fujiwara, Nagisa Arimitsu, Yuji Ueda, Sueshige Wakisaka, Tomoko Suzuki, Noboru Suzuki

Published in: Clinical Rheumatology | Issue 5/2019

Abstract

Objectives

We have previously demonstrated that the phylum Actinobacteria, the family Lactobacillaceae, and the genus Bifidobacterium increased in relative abundance of gut microbiota in patients with Behcet’s disease (BD). The phylum Firmicutes and the class Clostridia were predominant in the feces of normal individuals. The class Clostridia includes short-chain fatty acid–producing bacteria, important for the balance between regulatory T cells and helper T type 17 (Th17) cells. It is possible that the bacterial compositional alteration causes low intestinal short-chain fatty acid concentrations, leading to skewed immune functions in patients with BD.

Methods

To test the hypothesis, we examined species composition and gene functions from the 16S rRNA data by utilizing PICRUSt software.

Results

We have shown that relative abundance of Eggerthella lenta, Acidaminococcus species, Lactobacillus mucosae, Bifidobacterium bifidum, Lactobacillus iners, Streptococcus species, and Lactobacillus salivarius increased significantly in patients with BD. Relative abundance of Megamonas hypermegale, Butyrivibrio species, Streptococcus infantis, and Filifactor species increased significantly in normal individuals compared with BD patients. In the functional annotation analysis by PICRUSt, we found prevalent gene functions of the pentose phosphate pathway and the inosine monophosphate biosynthesis in patients with BD. The data suggested that BD gut microbes altered nucleic acid and fatty acid synthesis.

Conclusions

These compositional and functional alterations of gut microbes may accompany unfavorable molecular exchanges between intestinal immunocompetent cells and gut microbes, and these interactions may have an association with the immune aberration in patients with BD.

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Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behçet’s disease. N Engl J Med 341:1284–1291CrossRefPubMed

Shimizu J, Takai K, Takada E, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N (2016) Possible association of proinflammatory cytokines including IL1β and TNFα with enhanced Th17 cell differentiation in patients with Behcet’s disease. Clin Rheumatol 35:1857–1863. https://doi.org/10.1007/s10067-015-2966-2 CrossRefPubMed

Shimizu J, Takai K, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Yoshikawa H, Kaneko F, Suzuki T, Suzuki N (2012) Excessive CD4+ T cells co-expressing interleukin-17 and interferon-γ in patients with Behçet’s disease. Clin Exp Immunol 168:68–74. https://doi.org/10.1111/j.1365-2249.2011.04543.x CrossRefPubMedPubMedCentral

Shimizu J, Izumi T, Arimitsu N, Fujiwara N, Ueda Y, Wakisaka S, Yoshikawa H, Kaneko F, Suzuki T, Takai K, Suzuki N (2012) Skewed TGFβ/Smad signalling pathway in T cells in patients with Behçet’s disease. Clin Exp Rheumatol 30:S35–S39PubMed

Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–498. https://doi.org/10.1016/j.cell.2009.09.033 CrossRefPubMedPubMedCentral

Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S, Taniguchi T, Morita H, Hattori M, Honda K (2013) Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500:232–236. https://doi.org/10.1038/nature12331 CrossRefPubMed

Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N (2016) Bifidobacteria abundance-featured gut microbiota compositional change in patients with Behcet’s disease. PLoS One 11:e0153746. https://doi.org/10.1371/journal.pone.0153746 CrossRefPubMedPubMedCentral

Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–573. https://doi.org/10.1126/science.1241165 CrossRefPubMed

Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9:313–323. https://doi.org/10.1038/nri2515 CrossRefPubMedPubMedCentral

10.

Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, Centanni M, Cianchi F, Gotti R, Emmi L, Brigidi P, Bizzaro N, De Bellis G, Prisco D, Candela M, D’Elios MM (2015) Behçet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev 14:269–276. https://doi.org/10.1016/j.autrev.2014.11.009 CrossRefPubMed

11.

Ye Z, Zhang N, Wu C, Zhang X, Wang Q, Huang X, Du L, Cao Q, Tang J, Zhou C, Hou S, He Y, Xu Q, Xiong X, Kijlstra A, Qin N, Yang P (2018) A metagenomic study of the gut microbiome in Behcet’s disease. Microbiome 6:135. https://doi.org/10.1186/s40168-018-0520-6 CrossRefPubMedPubMedCentral

12.

Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z, Chen B, Li Y, Zhong H, Xie H, Jie Z, Chen W, Tang S, Xu X, Wang X, Cai X, Liu S, Xia Y, Li J, Qiao X, Al-Aama JY, Chen H, Wang L, Wu QJ, Zhang F, Zheng W, Li Y, Zhang M, Luo G, Xue W, Xiao L, Li J, Chen W, Xu X, Yin Y, Yang H, Wang J, Kristiansen K, Liu L, Li T, Huang Q, Li Y, Wang J (2015) The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 21:895–905. https://doi.org/10.1038/nm.3914 CrossRefPubMed

13.

Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H, Hattori M, Yamamura T (2015) Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One 10:e0137429. https://doi.org/10.1371/journal.pone.0137429 CrossRefPubMedPubMedCentral

14.

Bhakta BB, Brennan P, James TE, Chamberlain MA, Noble BA, Silman AJ (1999) Behçet’s disease: evaluation of a new instrument to measure clinical activity. Rheumatology (Oxford) 38:728–733CrossRef

15.

Morita H, Kuwahara T, Ohshima K, Sasamoto H, Itoh K, Hattori M, Hayashi T, Takami H (2007) An improved DNA isolation method for metagenomic analysis of the microbial flora of the human intestine. Microbes Environ 22:214–222CrossRef

16.

Kim SW, Suda W, Kim S, Oshima K, Fukuda S, Ohno H, Morita H, Hattori M (2013) Robustness of gut microbiota of healthy adults in response to probiotic intervention revealed by high-throughput pyrosequencing. DNA Res 20:241–253. https://doi.org/10.1093/dnares/dst006 CrossRefPubMedPubMedCentral

17.

Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, Beiko RG, Huttenhower C (2013) Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31:814–821. https://doi.org/10.1038/nbt.2676 CrossRefPubMedPubMedCentral

18.

Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12:R60. https://doi.org/10.1186/gb-2011-12-6-r60 CrossRefPubMedPubMedCentral

19.

Pearce EL, Poffenberger MC, Chang CH, Jones RG (2013) Fueling immunity: insights into metabolism and lymphocyte function. Science 342:1242454. https://doi.org/10.1126/science.1242454 CrossRefPubMedPubMedCentral

20.

Yang Z, Fujii H, Mohan SV, Goronzy JJ, Weyand CM (2013) Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. J Exp Med 210:2119–2134. https://doi.org/10.1084/jem.20130252 CrossRefPubMedPubMedCentral

21.

Gerriets VA, Kishton RJ, Nichols AG, Macintyre AN, Inoue M, Ilkayeva O, Winter PS, Liu X, Priyadharshini B, Slawinska ME, Haeberli L, Huck C, Turka LA, Wood KC, Hale LP, Smith PA, Schneider MA, MacIver NJ, Locasale JW, Newgard CB, Shinohara ML, Rathmell JC (2015) Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest 125:194–207. https://doi.org/10.1172/JCI76012 CrossRefPubMed

22.

Hevia A, Milani C, López P, Cuervo A, Arboleya S, Duranti S, Turroni F, González S, Suárez A, Gueimonde M, Ventura M, Sánchez B, Margolles A (2014) Intestinal dysbiosis associated with systemic lupus erythematosus. MBio 5:e01548–e01514. https://doi.org/10.1128/mBio.01548-14 CrossRefPubMedPubMedCentral

23.

Wen C, Zheng Z, Shao T, Liu L, Xie Z, Le Chatelier E, He Z, Zhong W, Fan Y, Zhang L, Li H, Wu C, Hu C, Xu Q, Zhou J, Cai S, Wang D, Huang Y, Breban M, Qin N, Ehrlich SD (2017) Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol 18:142. https://doi.org/10.1186/s13059-017-1271-6 CrossRefPubMedPubMedCentral

24.

Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T, Manasson J, Pamer EG, Littman DR, Abramson SB (2015) Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol 67:128–139. https://doi.org/10.1002/art.38892 CrossRefPubMedPubMedCentral

25.

Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2:e01202. https://doi.org/10.7554/eLife.01202 CrossRefPubMedPubMedCentral

26.

Pianta A, Arvikar S, Strle K, Drouin EE, Wang Q, Costello CE, Steere AC (2017) Evidence of the immune relevance of Prevotella copri, a gut microbe, in patients with rheumatoid arthritis. Arthritis Rheumatol 69:964–975. https://doi.org/10.1002/art.40003 CrossRefPubMedPubMedCentral

27.

Cekanaviciute E, Yoo BB, Runia TF, Debelius JW, Singh S, Nelson CA, Kanner R, Bencosme Y, Lee YK, Hauser SL, Crabtree-Hartman E, Sand IK, Gacias M, Zhu Y, Casaccia P, Cree BAC, Knight R, Mazmanian SK, Baranzini SE (2017) Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A 114:10713–10718. https://doi.org/10.1073/pnas.1711235114 CrossRefPubMedPubMedCentral

28.

Seoudi N, Bergmeier LA, Drobniewski F, Paster B, Fortune F (2015) The oral mucosal and salivary microbial community of Behçet’s syndrome and recurrent aphthous stomatitis. J Oral Microbiol 7:27150. https://doi.org/10.3402/jom.v7.27150 CrossRefPubMed

29.

Coit P, Mumcu G, Ture-Ozdemir F, Unal AU, Alpar U, Bostanci N, Ergun T, Direskeneli H, Sawalha AH (2016) Sequencing of 16S rRNA reveals a distinct salivary microbiome signature in Behçet’s disease. Clin Immunol 169:28–35. https://doi.org/10.1016/j.clim.2016.06.002 CrossRefPubMed

30.

Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131:33–45CrossRefPubMedPubMedCentral

31.

Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, Punit S, Karlsson M, Bry L, Glickman JN, Gordon JI, Onderdonk AB, Glimcher LH (2010) Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8:292–300. https://doi.org/10.1016/j.chom.2010.08.004 CrossRefPubMedPubMedCentral

32.

Haghikia A, Jörg S, Duscha A, Berg J, Manzel A, Waschbisch A, Hammer A, Lee DH, May C, Wilck N, Balogh A, Ostermann AI, Schebb NH, Akkad DA, Grohme DA, Kleinewietfeld M, Kempa S, Thöne J, Demir S, Müller DN, Gold R, Linker RA (2015) Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 43:817–829. https://doi.org/10.1016/j.immuni.2015.09.007 CrossRefPubMed

33.

Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–450. https://doi.org/10.1038/nature12721 CrossRefPubMed

34.

De Paepe K, Kerckhof FM, Verspreet J, Courtin CM, Van de Wiele T (2017) Inter-individual differences determine the outcome of wheat bran colonization by the human gut microbiome. Environ Microbiol 19:3251–3267. https://doi.org/10.1111/1462-2920.13819 CrossRefPubMed

35.

Duncan SH, Russell WR, Quartieri A, Rossi M, Parkhill J, Walker AW, Flint HJ (2016) Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid. Environ Microbiol 18:2214–2225. https://doi.org/10.1111/1462-2920.13158 CrossRefPubMedPubMedCentral

36.

Paillard D, McKain N, Chaudhary LC, Walker ND, Pizette F, Koppova I, McEwan NR, Kopecný J, Vercoe PE, Louis P, Wallace RJ (2007) Relation between phylogenetic position, lipid metabolism and butyrate production by different Butyrivibrio-like bacteria from the rumen. Antonie Van Leeuwenhoek 91:417–422CrossRefPubMed

37.

Van den Abbeele P, Belzer C, Goossens M, Kleerebezem M, De Vos WM, Thas O, De Weirdt R, Kerckhof FM, Van de Wiele T (2013) Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. ISME J 7:949–961. https://doi.org/10.1038/ismej.2012.158 CrossRefPubMed

38.

Rouxel O, Da Silva J, Beaudoin L, Nel I, Tard C, Cagninacci L, Kiaf B, Oshima M, Diedisheim M, Salou M, Corbett A, Rossjohn J, McCluskey J, Scharfmann R, Battaglia M, Polak M, Lantz O, Beltrand J, Lehuen A (2017) Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nat Immunol 18:1321–1331. https://doi.org/10.1038/ni.3854 CrossRefPubMedPubMedCentral

39.

Khan MT, Duncan SH, Stams AJ, van Dijl JM, Flint HJ, Harmsen HJ (2012) The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic-anoxic interphases. ISME J 6:1578–1585. https://doi.org/10.1038/ismej.2012.5 CrossRefPubMedPubMedCentral

40.

Ghosal A, Lambrecht N, Subramanya SB, Kapadia R, Said HM (2013) Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption. Am J Physiol Gastrointest Liver Physiol 304:G64–G71. https://doi.org/10.1152/ajpgi.00379.2012 CrossRefPubMed

Title: Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behcet’s disease (210 characters)
Authors: Jun Shimizu
Takao Kubota
Erika Takada
Kenji Takai
Naruyoshi Fujiwara
Nagisa Arimitsu
Yuji Ueda
Sueshige Wakisaka
Tomoko Suzuki
Noboru Suzuki
Publication date: 01-05-2019
Publisher: Springer London
Keywords: Streptococci
Respiratory Microbiota
Published in: Clinical Rheumatology / Issue 5/2019
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-018-04419-8

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