Skip to main content
SpringerLink
Log in

Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders. Here, we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia (ITP) patients and 52 healthy controls. Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally, and classifier based on species markers distinguished individuals with ITP from healthy controls. In particular, the abundance of Ruminococcus gnavus, Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-naïve ITP patients, and the alterations of microbial species were correlated with clinical indices. Functionally, the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP, which may contribute to the onset of ITP by affecting the immune system. Furthermore, we found that corticosteroid treatment affected the gut microbiome of ITP. Compared with corticosteroid-sensitive ITP patients, we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome, which was different from that of the treatment-naïve ITP patients. Together, we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albertsen, M., Hugenholtz, P., Skarshewski, A., Nielsen, K.L., Tyson, G. W., and Nielsen, P.H. (2013). Genome sequences of rare, uncultured bacteria obtained by differential coverage binning of multiple metagenomes. Nat Biotechnol 31, 533–538.

    CAS  PubMed  Google Scholar 

  • Asahi, A., Nishimoto, T., Okazaki, Y., Suzuki, H., Masaoka, T., Kawakami, Y., Ikeda, Y., and Kuwana, M. (2008). Helicobacter pylori eradication shifts monocyte Fcy receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients. J Clin Invest 118, 2939–2949.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Audia, S., Mahévas, M., Samson, M., Godeau, B., and Bonnotte, B. (2017). Pathogenesis of immune thrombocytopenia. Autoimmun Rev 16, 620–632.

    CAS  PubMed  Google Scholar 

  • Azzouz, D., Omarbekova, A., Heguy, A., Schwudke, D., Gisch, N., Rovin, B.H., Caricchio, R., Buyon, J.P., Alekseyenko, A.V., and Silverman, G. J. (2019). Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis 78, 947–956.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bettaieb, A., Oksenhendler, E., Duedari, N., and Bierling, P. (1996). Cross-reactive antibodies between HIV-gp120 and platelet gpIIIa (CD61) in HIV-related immune thrombocytopenic purpura. Clin Exp Immunol 103, 19–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Borody, T., Campbell, J., Torres, M., Nowak, A., and Leis, S. (2011). Reversal of idiopathic thrombocytopenic purpura [ITP] with fecal microbiota transplantation [FMT]. Am J Gastroenterol 106, S352.

    Google Scholar 

  • Brandt, L.J., Aroniadis, O.C., Mellow, M., Kanatzar, A., Kelly, C., Park, T., Stollman, N., Rohlke, F., and Surawicz, C. (2012). Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 107, 1079–1087.

    PubMed  Google Scholar 

  • Breunis, W.B., van Mirre, E., Bruin, M., Geissler, J., de Boer, M., Peters, M., Roos, D., de Haas, M., Koene, H.R., and Kuijpers, T.W. (2008). Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura. Blood 111, 1029–1038.

    CAS  PubMed  Google Scholar 

  • Chiang, J.Y.L. (2009). Bile acids: regulation of synthesis. J Lipid Res 50, 1955–1966.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chua, H.H., Chou, H.C., Tung, Y.L., Chiang, B.L., Liao, C.C., Liu, H.H., and Ni, Y.H. (2018). Intestinal dysbiosis featuring abundance of Ruminococcus gnavus associates with allergic diseases in infants. Gastroenterology 154, 154–167.

    PubMed  Google Scholar 

  • Clemente, J.C., Ursell, L.K., Parfrey, L.W., and Knight, R. (2012). The impact of the gut microbiota on human health: an integrative view. Cell 148, 1258–1270.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Collison, J. (2019). Gut microbiota linked to kidney disease in SLE. Nat Rev Rheumatol 15, 188.

    PubMed  Google Scholar 

  • Cooper, N., and Ghanima, W. (2019). Immune thrombocytopenia. N Engl J Med 381, 945–955.

    PubMed  Google Scholar 

  • Dao, M.C., Everard, A., Aron-Wisnewsky, J., Sokolovska, N., Prifti, E., Verger, E.O., Kayser, B.D., Levenez, F., Chilloux, J., Hoyles, L., et al. (2016). Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65, 426–436.

    CAS  PubMed  Google Scholar 

  • Derrien, M., Belzer, C., and de Vos, W.M. (2017). Akkermansia muciniphila and its role in regulating host functions. Microb Pathogenesis 106, 171–181.

    Google Scholar 

  • Eckburg, P.B., Bik, E.M., Bernstein, C.N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S.R., Nelson, K.E., and Relman, D.A. (2005). Diversity of the human intestinal microbial flora. Science 308, 1635–1638.

    PubMed  PubMed Central  Google Scholar 

  • Fiorucci, S., and Distrutti, E. (2015). Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med 21, 702–714.

    CAS  PubMed  Google Scholar 

  • Forslund, K., Hildebrand, F., Nielsen, T., Falony, G., Le Chatelier, E., Sunagawa, S., Prifti, E., Vieira-Silva, S., Gudmundsdottir, V., Krogh Pedersen, H., et al. (2015). Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528, 262–266.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Francis, O.E., Bendall, M., Manimaran, S., Hong, C., Clement, N.L., Castro-Nallar, E., Snell, Q., Schaalje, G.B., Clement, M.J., Crandall, K. A., et al. (2013). Pathoscope: Species identification and strain attribution with unassembled sequencing data. Genome Res 23, 1721–1729.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Franzosa, E.A., Sirota-Madi, A., Avila-Pacheco, J., Fornelos, N., Haiser, H. J., Reinker, S., Vatanen, T., Hall, A.B., Mallick, H., McIver, L.J., et al. (2019). Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol 4, 293–305.

    CAS  PubMed  Google Scholar 

  • Frydman, G.H., Davis, N., Beck, P.L., and Fox, J.G. (2015). Helicobacter pylori eradication in patients with immune thrombocytopenic purpura: A review and the role of biogeography. Helicobacter 20, 239–251.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fu, L., Niu, B., Zhu, Z., Wu, S., and Li, W. (2012). CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 28, 3150–3152.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Furumitsu, Y., Yukioka, K., Yukioka, M., Ochi, T., Morishima, Y., Matsui-Yuasa, I., Otani, S., Inaba, M., Nishizawa, Y., and Morii, H. (2000). Interleukin-1beta induces elevation of spermidine/spermine N1-acetyl-transferase activity and an increase in the amount of putrescine in synovial adherent cells from patients with rheumatoid arthritis. J Rheumatol 27, 1352–1357.

    CAS  PubMed  Google Scholar 

  • Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450.

    CAS  PubMed  Google Scholar 

  • Goleva, E., Harris, J.K., Robertson, C.E., Jackson, L.P., Martin, R.J., and Leung, D.Y.M. (2017). Airway microbiome and responses to corticosteroids in corticosteroid-resistant asthma patients treated with acid suppression medications. J Allergy Clin Immunol 140, 860–862.e1.

    CAS  PubMed  Google Scholar 

  • Goleva, E., Jackson, L.P., Harris, J.K., Robertson, C.E., Sutherland, E.R., Hall, C.F., Good Jr., J.T., Gelfand, E.W., Martin, R.J., and Leung, D.Y. M. (2013). The effects of airway microbiome on corticosteroid responsiveness in asthma. Am J Respir Crit Care Med 188, 1193–1201.

    CAS  PubMed  PubMed Central  Google Scholar 

  • He, Y., Xu, L.L., Feng, F.E., Wang, Q.M., Zhu, X.L., Wang, C.C., Zhang, J. M., Fu, H.X., Xu, L.P., Liu, K.Y., et al. (2018). Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF-κB/SMAD pathway in patients with immune thrombocytopenia. Br J Haematol 180, 395–411.

    CAS  PubMed  Google Scholar 

  • Hevia, A., Milani, C., López, P., Cuervo, A., Arboleya, S., Duranti, S., Turroni, F., Gonzàlez, S., Suàrez, A., Gueimonde, M., et al. (2014). Intestinal dysbiosis associated with systemic lupus erythematosus. mBio 5.

  • Huson, D.H., Auch, A.F., Qi, J., and Schuster, S.C. (2007). MEGAN analysis of metagenomic data. Genome Res 17, 377–386.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Imhann, F., Bonder, M.J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E.F., Jankipersadsing, S.A., Cenit, M.C., Harmsen, H.J.M., et al. (2016). Proton pump inhibitors affect the gut microbiome. Gut 65, 740–748.

    CAS  PubMed  Google Scholar 

  • Iwamura, C., Bouladoux, N., Belkaid, Y., Sher, A., and Jankovic, D. (2017). Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis. Blood 129, 171–176.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson, M.A., Goodrich, J.K., Maxan, M.E., Freedberg, D.E., Abrams, J. A., Poole, A.C., Sutter, J.L., Welter, D., Ley, R.E., Bell, J.T., et al. (2016). Proton pump inhibitors alter the composition of the gut microbiota. Gut 65, 749–756.

    PubMed  Google Scholar 

  • Jackson, S., Beck, P.L., Pineo, G.F., and Poon, M.C. (2005). Helicobacter pylori eradication: novel therapy for immune thrombocytopenic purpura? A review of the literature. Am J Hematol 78, 142–150.

    CAS  PubMed  Google Scholar 

  • Jie, Z., Xia, H., Zhong, S.L., Feng, Q., Li, S., Liang, S., Zhong, H., Liu, Z., Gao, Y., Zhao, H., et al. (2017). The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun 8, 845.

    PubMed  PubMed Central  Google Scholar 

  • Kinnebrew, M.A., Buffie, C.G., Diehl, G.E., Zenewicz, L.A., Leiner, I., Hohl, T.M., Flavell, R.A., Littman, D.R., and Pamer, E.G. (2012). Interleukin 23 production by intestinal CD103 CD11b dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36, 276–287.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kong, Y., Cao, X.N., Zhang, X.H., Shi, M.M., Lai, Y.Y., Wang, Y., Xu, L.P., Chang, Y.J., and Huang, X.J. (2018). Atorvastatin enhances bone marrow endothelial cell function in corticosteroid-resistant immune thrombocytopenia patients. Blood 131, 1219–1233.

    CAS  PubMed  Google Scholar 

  • Kuwana, M., Asahi, A., Suzuki, H., Okazaki, Y., and Ikeda, Y. (2006). Eradication of Helicobacter pylori shifts the balance of Fcy receptors on monocytes toward the inhibitory FcyRIIB in patients with chronic ITP. Blood 108, 1082.

    Google Scholar 

  • Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.M., Kennedy, S., et al. (2013). Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546.

    CAS  PubMed  Google Scholar 

  • Lewis, J.D., Chen, E.Z., Baldassano, R.N., Otley, A.R., Griffiths, A.M., Lee, D., Bittinger, K., Bailey, A., Friedman, E.S., Hoffmann, C., et al. (2015). Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe 18, 489–500.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li, J., Ma, S., Shao, L., Ma, C., Gao, C., Zhang, X.H., Hou, M., and Peng, J. (2017). Inflammation-related gene polymorphisms associated with primary immune thrombocytopenia. Front Immunol 8.

  • Li, R., Yu, C., Li, Y., Lam, T.W., Yiu, S.M., Kristiansen, K., and Wang, J. (2009). SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25, 1966–1967.

    CAS  PubMed  Google Scholar 

  • Li, W., and Godzik, A. (2006). Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 22, 1658–1659.

    CAS  PubMed  Google Scholar 

  • Liu, C., Cheng, L., Ji, L., Li, F., Zhan, Y., Wu, B., Ke, Y., Chen, P., Hua, F., Yuan, L., et al. (2020). Intestinal microbiota dysbiosis play a role in pathogenesis of patients with primary immune thrombocytopenia. Thromb Res 190, 11–19.

    CAS  PubMed  Google Scholar 

  • Liu, R., Hong, J., Xu, X., Feng, Q., Zhang, D., Gu, Y., Shi, J., Zhao, S., Liu, W., Wang, X., et al. (2017). Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat Med 23, 859–868.

    CAS  PubMed  Google Scholar 

  • Luo, Y., Chen, G.L., Hannemann, N., Ipseiz, N., Krönke, G., Bäuerle, T., Munos, L., Wirtz, S., Schett, G., and Bozec, A. (2015). Microbiota from obese mice regulate hematopoietic stem cell differentiation by altering the bone niche. Cell Metab 22, 886–894.

    CAS  PubMed  Google Scholar 

  • Malnick’ S.D.H., Oppenheim, A., and Melzer, E. (2015). Immune thrombocytopenia caused by fecal microbial transplantation in a patient with severe recurrent clostridium difficile infection. J Clin Gastroenterol 49, 888–889.

    Google Scholar 

  • Manzo, V.E., and Bhatt, A.S. (2015). The human microbiome in hematopoiesis and hematologic disorders. Blood 126, 311–318.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maynard, C.L., Elson, C.O., Hatton, R.D., and Weaver, C.T. (2012). Reciprocal interactions of the intestinal microbiota and immune system. Nature 489, 231–241.

    CAS  PubMed  PubMed Central  Google Scholar 

  • McMillan, R., and Nugent, D. (2005). The effect of antiplatelet autoantibodies on megakaryocytopoiesis. Int J Hematol 81, 94–99.

    CAS  PubMed  Google Scholar 

  • Miquel, S., Martín, R., Rossi, O., Bermúdez-Humaràn, L.G., Chatel, J.M., Sokol, H., Thomas, M., Wells, J.M., and Langella, P. (2013). Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol 16, 255–261.

    CAS  PubMed  Google Scholar 

  • Moreno, B., Fernandez-Diez, B., Di Penta, A., and Villoslada, P. (2010). Preclinical studies of methylthioadenosine for the treatment of multiple sclerosis. Mult Scler 16, 1102–1108.

    CAS  PubMed  Google Scholar 

  • Nielsen, H.B., Almeida, M., Juncker, A.S., Rasmussen, S., Li, J., Sunagawa, S., Plichta, D.R., Gautier, L., Pedersen, A.G., Le Chatelier, E., et al. (2014). Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol 32, 822–828.

    CAS  PubMed  Google Scholar 

  • Nomura, S., Matsuzaki, T., Ozaki, Y., Yamaoka, M., Yoshimura, C., Katsura, K., Xie, G.L., Kagawa, H., Ishida, T., and Fukuhara, S. (1998). Clinical significance of HLA-DRB1*0410 in Japanese patients with idiopathic thrombocytopenic purpura. Blood 91, 3616–3622.

    CAS  PubMed  Google Scholar 

  • Patil, K.R., and Nielsen, J. (2005). Uncovering transcriptional regulation of metabolism by using metabolic network topology. Proc Natl Acad Sci USA 102, 2685–2689.

    CAS  PubMed  Google Scholar 

  • Plaza-Díaz, J., Ruiz-Ojeda, F.J., Vilchez-Padial, L.M., and Gil, A. (2017). Evidence of the anti-inflammatory effects of probiotics and synbiotics in intestinal chronic diseases. Nutrients 9, 555.

    PubMed Central  Google Scholar 

  • Png, C.W., Linden, S.K., Gilshenan, K.S., Zoetendal, E.G., McSweeney, C. S., Sly, L.I., McGuckin, M.A., and Florin, T.H.J. (2010). Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol 105, 2420–2428.

    CAS  PubMed  Google Scholar 

  • Provan, D., Arnold, D.M., Bussel, J.B., Chong, B.H., Cooper, N., Gernsheimer, T., Ghanima, W., Godeau, B., Gonzàlez-López, T.J., Grainger, J., et al. (2019). Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 3, 3780–3817.

    PubMed  PubMed Central  Google Scholar 

  • Provan, D., Stasi, R., Newland, A.C., Blanchette, V.S., Bolton-Maggs, P., Bussel, J.B., Chong, B.H., Cines, D.B., Gernsheimer, T.B., Godeau, B., et al. (2010). International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 115, 168–186.

    CAS  PubMed  Google Scholar 

  • Qi, X., Li, X., Zhao, Y., Wu, X., Chen, F., Ma, X., Zhang, F., and Wu, D. (2018). Treating steroid refractory intestinal acute graft-vs.-host disease with fecal microbiota transplantation: A pilot study. Front Immunol 9, 2195.

    PubMed  PubMed Central  Google Scholar 

  • Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60.

    CAS  PubMed  Google Scholar 

  • Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K.S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., et al. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Qin, N., Yang, F., Li, A., Prifti, E., Chen, Y., Shao, L., Guo, J., Le Chatelier, E., Yao, J., Wu, L., et al. (2014). Alterations of the human gut microbiome in liver cirrhosis. Nature 513, 59–64.

    CAS  PubMed  Google Scholar 

  • Rooks, M.G., and Garrett, W.S. (2016). Gut microbiota, metabolites and host immunity. Nat Rev Immunol 16, 341–352.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Satoh, T., Miyazaki, K., Shimohira, A., Amano, N., Okazaki, Y., Nishimoto, T., Akahoshi, T., Munekata, S., Kanoh, Y., Ikeda, Y., et al. (2013). Fcy receptor IIB gene polymorphism in adult Japanese patients with primary immune thrombocytopenia. Blood 122, 1991–1992.

    CAS  PubMed  Google Scholar 

  • Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humaràn, L. G., Gratadoux, J.J., Blugeon, S., Bridonneau, C., Furet, J.P., Corthier, G., et al. (2008). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA 105, 16731–16736.

    CAS  PubMed  Google Scholar 

  • Stat, M., Pochon, X., Franklin, E.C., Bruno, J.F., Casey, K.S., Selig, E.R., and Gates, R.D. (2013). The distribution of the thermally tolerant symbiont lineage (Symbiodinium clade D) in corals from Hawaii: correlations with host and the history of ocean thermal stress. Ecol Evol 3, 1317–1329.

    PubMed  PubMed Central  Google Scholar 

  • Suzuki, T., Matsushima, M., Masui, A., Watanabe, K., Takagi, A., Ogawa, Y., Shirai, T., and Mine, T. (2005). Effect of Helicobacter pylori eradication in patients with chronic idiopathic thrombocytopenic purpura—A randomized controlled trial. Am J Gastroenterol 100, 1265–1270.

    PubMed  Google Scholar 

  • Takahashi, T., Yujiri, T., Shinohara, K., Inoue, Y., Sato, Y., Fujii, Y., Okubo, M., Zaitsu, Y., Ariyoshi, K., Nakamura, Y., et al. (2004). Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Br J Haematol 124, 91–96.

    CAS  PubMed  Google Scholar 

  • Thomas, T.J., Meryhew, N.L., and Messner, R.P. (1990). Enhanced binding of lupus sera to the polyamine-induced left-handed Z-DNA form of polynucleotides. Arthritis Rheum 33, 356–365.

    CAS  PubMed  Google Scholar 

  • Tsutsumi, Y., Kanamori, H., Yamato, H., Ehira, N., Kawamura, T., Umehara, S., Mori, A., Obara, S., Ogura, N., Tanaka, J., et al. (2005). Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura. Ann Hematol 84, 807–811.

    CAS  PubMed  Google Scholar 

  • Wang, Q., Li, J., Yu, T.S., Liu, Y., Li, K., Liu, S., Liu, Y., Feng, Q., Zhang, L., Li, G.S., et al. (2019). Disrupted balance of CD4+ T-cell subsets in bone marrow of patients with primary immune thrombocytopenia. Int J Biol Sci 15, 2798–2814.

    PubMed  PubMed Central  Google Scholar 

  • Wang, T., Zhao, H., Ren, H., Guo, J., Xu, M., Yang, R., and Han, Z.C. (2005). Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica 90, 914–923.

    CAS  PubMed  Google Scholar 

  • Wen, C., Zheng, Z., Shao, T., Liu, L., Xie, Z., Le Chatelier, E., He, Z., Zhong, W., Fan, Y., Zhang, L., et al. (2017). Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol 18, 142.

    PubMed  PubMed Central  Google Scholar 

  • Wu, H., Esteve, E., Tremaroli, V., Khan, M.T., Caesar, R., Mannerås-Holm, L., Ståhlman, M., Olsson, L.M., Serino, M., Planas-Fèlix, M., et al. (2017). Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med 23, 850–858.

    CAS  PubMed  Google Scholar 

  • Xing, J., Ying, Y., Mao, C., Liu, Y., Wang, T., Zhao, Q., Zhang, X., Yan, F., and Zhang, H. (2018). Hypoxia induces senescence of bone marrow mesenchymal stem cells via altered gut microbiota. Nat Commun 9, 2020.

    PubMed  PubMed Central  Google Scholar 

  • Zhang, J.M., Feng, F.E., Wang, Q.M., Zhu, X.L., Fu, H.X., Xu, L.P., Liu, K. Y., Huang, X.J., and Zhang, X.H. (2016). Platelet-derived growth factor-BB protects mesenchymal stem cells (MSCs) derived from immune thrombocytopenia patients against apoptosis and senescence and maintains MSC-mediated immunosuppression. Stem Cells Transl Med 5, 1631–1643.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, W., Nardi, M.A., Borkowsky, W., Li, Z., and Karpatkin, S. (2009). Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood 113, 4086–4093.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, X., Zhang, D., Jia, H., Feng, Q., Wang, D., Liang, D., Wu, X., Li, J., Tang, L., Li, Y., et al. (2015). The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 21, 895–905.

    CAS  PubMed  Google Scholar 

  • Zhu, W., Lomsadze, A., and Borodovsky, M. (2010). Ab initio gene identification in metagenomic sequences. Nucleic Acids Res 38, e132.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Beijing Municipal Science and Technology Commission (Z171100001017084), Natural Science Foundation of Beijing Municipality (7171013 and H2018206423), Key Program of National Natural Science Foundation of China (81730004), the National Natural Science Foundation of China (81670116 and 81970113), and National Key Research and Development Program of China (2017YFA0105503).

Author information

Author notes

  1. Contributed equally to this work

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China

    Yanan Wang, Fengqi Liu, Gaochao Zhang, Yan Su, Xueyan Sun, Qi Chen, Chencong Wang, Haixia Fu, Yun He, Xiaolu Zhu, Xiao Liu, Meng Lv, Xiangyu Zhao, Xiaosu Zhao, Xiaojun Huang & Xiaohui Zhang

  2. Collaborative Innovation Centre of Hematology, Peking University, Beijing, 100044, China

    Yanan Wang, Fengqi Liu, Gaochao Zhang, Yan Su, Xueyan Sun, Qi Chen, Chencong Wang, Haixia Fu, Yun He, Xiaolu Zhu, Xiao Liu, Meng Lv, Xiangyu Zhao, Xiaosu Zhao, Xiaojun Huang & Xiaohui Zhang

  3. National Clinical Research Center for Hematologic Disease, Beijing, 100044, China

    Yanan Wang, Fengqi Liu, Gaochao Zhang, Yan Su, Xueyan Sun, Qi Chen, Chencong Wang, Haixia Fu, Yun He, Xiaolu Zhu, Xiao Liu, Meng Lv, Xiangyu Zhao, Xiaosu Zhao, Xiaojun Huang & Xiaohui Zhang

  4. CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China

    Yueying Li & Qianfei Wang

  5. National Center for Bioinformation, Beijing, 100101, China

    Yueying Li & Qianfei Wang

  6. University of Chinese Academy of Sciences, Beijing, 100049, China

    Qianfei Wang

Authors
  1. Yanan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fengqi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gaochao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xueyan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chencong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haixia Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yun He
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiaolu Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Meng Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Xiangyu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Xiaosu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yueying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Qianfei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Xiaojun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Xiaohui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaohui Zhang.

Additional information

Compliance and ethics

The author(s) declare that they have no conflict of interest.

Supporting Figures

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Liu, F., Zhang, G. et al. Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia. Sci. China Life Sci. 64, 766–783 (2021). https://doi.org/10.1007/s11427-020-1788-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-020-1788-2

Search

Navigation