DOI QR코드

DOI QR Code

Gut Microbiome Alterations and Functional Prediction in Chronic Spontaneous Urticaria Patients

  • Zhang, Xinyue (Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University) ;
  • Zhang, Jun (College of Science, Northwest University) ;
  • Chu, Zhaowei (Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University) ;
  • Shi, Linjing (Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University) ;
  • Geng, Songmei (Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University) ;
  • Guo, Kun (Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University)
  • Received : 2020.12.09
  • Accepted : 2021.03.16
  • Published : 2021.05.28

Abstract

The effects of the gut microbiome on both allergy and autoimmunity in dermatological diseases have been indicated in several recent studies. Chronic spontaneous urticaria (CSU) is a disease involving allergy and autoimmunity, and there is no report detailing the role of microbiota alterations in its development. This study was performed to identify the fecal microbial composition of CSU patients and investigate the different compositions and potential genetic functions on the fecal microbiota between CSU patients and normal controls. The gut microbiota of CSU patients and healthy individuals were obtained by 16s rRNA massive sequencing. Gut microbiota diversity and composition were compared, and bioinformatics analysis of the differences was performed. The gut microbiota composition results showed that Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia were dominant microbiota in CSU patients. The differential analysis showed that relative abundance of the Proteobacteria (p = 0.03), Bacilli (p = 0.04), Enterobacterales (p = 0.03), Enterobacteriaceae (p = 0.03) was significantly increased in CSU patients. In contrast, the relative abundance of Megamonas, Megasphaera, and Dialister (all p < 0.05) in these patients significantly decreased compared with healthy controls. The different microbiological compositions impacted normal gastrointestinal functions based on function prediction, resulting in abnormal pathways, including transport and metabolism. We found CSU patients exhibited gut microbiota dysbiosis compared with healthy controls. Our results indicated CSU is associated with gut microbiota dysbiosis and pointed out that the bacterial taxa increased in CSU patients, which might be involved in the pathogenesis of CSU. These results provided clues for future microbial-based therapies on CSU.

Keywords

Acknowledgement

We appreciate the financial support provided by the National Natural Science Foundation of China. Moreover, we are indebted to all study participants involved in the study. We are grateful to the support provided by the Second Hospital Affiliated Hospital and Xi'an Jiaotong University.

References

  1. Poonawalla T, and Kelly B. 2009. Urticaria : a review. Am. J. Clin. Dermatol. 10: 9-21. https://doi.org/10.2165/0128071-200910010-00002
  2. The definition, diagnostic testing, and management of chronic inducible urticarias - The EAACI/GA2LEN/EDF/ UNEV consensus recommendations 2016 update and revision.
  3. Kaplan AP. 2020. Diagnosis and treatment of chronic spontaneous urticaria, ALLERGY.
  4. Bracken SJ, Abraham S, MacLeod AS. 2019. Autoimmune theories of chronic spontaneous urticaria. Front. Immunol. 10: 627. https://doi.org/10.3389/fimmu.2019.00627
  5. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. 2007. The human microbiome project. Nature 449: 804-810. https://doi.org/10.1038/nature06244
  6. Pascal M, Perez-Gordo M, Caballero T, Escribese MM, Lopez LM, Luengo O, et al. 2018. Microbiome and allergic diseases. Front. Immunol. 9: 1584. https://doi.org/10.3389/fimmu.2018.01584
  7. Lindberg M, Soderquist B. 2017. Atopic dermatitis and gut microbiota. Br. J. Dermatol. 176: 297-298. https://doi.org/10.1111/bjd.15276
  8. Marrs T, Flohr C. 2016. The role of skin and gut microbiota in the development of atopic eczema. Br. J. Dermatol. 175 Suppl 2: 13-18. https://doi.org/10.1111/bjd.14907
  9. Hidalgo-Cantabrana C, Gomez J, Delgado S, Requena-Lopez S, Queiro-Silva R, and Margolles A, et al. 2019. Gut microbiota dysbiosis in a cohort of patients with psoriasis. Br. J. Dermatol. 181: 1287-1295. https://doi.org/10.1111/bjd.17931
  10. Huang L, Gao R, Yu N, Zhu Y, Ding Y, Qin H. 2019. Dysbiosis of gut microbiota was closely associated with psoriasis. Sci. China Life Sci. 62: 807-815. https://doi.org/10.1007/s11427-018-9376-6
  11. Codoner FM, Ramirez-Bosca A, Climent E, Carrion-Gutierrez M, Guerrero M, Perez-Orquin JM, et al. 2018. Gut microbial composition in patients with psoriasis. Sci. Rep. 8: 3812. https://doi.org/10.1038/s41598-018-22125-y
  12. Tang MF, Sy HY, Kwok JS, Tam WH, Hon KL, Tung CK, et al. 2016. Eczema susceptibility and composition of faecal microbiota at 4 weeks of age: a pilot study in Chinese infants. Br. J. Dermatol. 174: 898-900. https://doi.org/10.1111/bjd.14205
  13. Pedersen E, Skov L, Thyssen J, Jensen P. 2018. Role of the gut microbiota in atopic dermatitis: a systematic review. Acta Derm. Venereol. 99: 5-11.
  14. Lee S, Lee E, Park YM, Hong S. 2018. Microbiome in the gut-skin axis in atopic dermatitis. Allergy Asthma Immunol. Res. 10: 354-362. https://doi.org/10.4168/aair.2018.10.4.354
  15. Manfredo VS, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, et al. 2018. Translocation of a gut pathobiont drives autoimmunity in mice and humans, Sci. 359: 1156-1161. https://doi.org/10.1126/science.aar7201
  16. Rezazadeh A, Shahabi S, Bagheri M, Nabizadeh E, Jazani NH. 2018. The protective effect of Lactobacillus and Bifidobacterium as the gut microbiota members against chronic urticaria. Int. Immunopharmacol. 59: 168-173. https://doi.org/10.1016/j.intimp.2018.04.007
  17. Nabizadeh E, Jazani NH, Bagheri M, Shahabi S. 2017. Association of altered gut microbiota composition with chronic urticaria. Ann. Allergy Asthma. Immunol. 119: 48-53. https://doi.org/10.1016/j.anai.2017.05.006
  18. Lu T, Chen Y, Guo Y, Sun J, Shen W, Yuan M, et al. 2019. Altered gut microbiota diversity and composition in chronic urticaria. Dis. Markers 2019: 6417471.
  19. Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, et al. 2009. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 75: 7537-7541. https://doi.org/10.1128/AEM.01541-09
  20. DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie E L, Keller K, et al. 2006. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 72: 5069-5072. https://doi.org/10.1128/AEM.03006-05
  21. Kemp PF, and Aller JY (2004) Bacterial diversity in aquatic and other environments: what 16S rDNA libraries can tell us. FEMS Microbiol. Ecol. 47: 161-177. https://doi.org/10.1016/S0168-6496(03)00257-5
  22. Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. 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
  23. Bisgaard H, Li N, Bonnelykke K, Chawes BL, Skov T, Paludan-Muller G, et al. 2011. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J. Allergy Clin. Immunol. 128: 646-652. https://doi.org/10.1016/j.jaci.2011.04.060
  24. Tan L, Zhao S, Zhu W, Wu L, Li J, Shen M, et al. 2018. The Akkermansia muciniphila is a gut microbiota signature in psoriasis. Exp. Dermatol. 27: 144-149. https://doi.org/10.1111/exd.13463
  25. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. 2005. Diversity of the human intestinal microbial flora. Science 308: 1635-1638. https://doi.org/10.1126/science.1110591
  26. Qin J, Li R, Raes J, Arumugam M, Burgdorf K, Manichanh C, et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464: 59-65. https://doi.org/10.1038/nature08821
  27. Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, et al. 2010. Disordered microbial communities in asthmatic airways. PLoS One 5: e8578. https://doi.org/10.1371/journal.pone.0008578
  28. Huang YJ, Nelson CE, Brodie EL, Desantis TZ, Baek MS, Liu J, et al. 2011. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J. Allergy Clin. Immunol. 127: 372-381. https://doi.org/10.1016/j.jaci.2010.10.048
  29. Moy AP, Murali M, Nazarian RM. 2016. Identification of a Th2- and Th17-skewed immune phenotype in chronic urticaria with Th22 reduction dependent on autoimmunity and thyroid disease markers. J. Cutan. Pathol. 43: 372-378. https://doi.org/10.1111/cup.12673
  30. Ling Z, Jin C, Xie T, Cheng Y, Li L, Wu N. 2016. Alterations in the fecal microbiota of patients with HIV-1 infection: an observational study in a Chinese population. Sci. Rep. 6: 30673. https://doi.org/10.1038/srep30673
  31. Xu H, Wang X, Feng W, Liu Q, Zhou S, Liu Q, et al. 2020. The gut microbiota and its interactions with cardiovascular disease. Microb. Biotechnol. 13: 637-656. https://doi.org/10.1111/1751-7915.13524
  32. Karaolis DK, Somara S, Maneval DJ, Johnson JA, Kaper JB. 1999. A bacteriophage encoding a pathogenicity island, a type-IV pilus and a phage receptor in cholera bacteria. Nature 399: 375-379. https://doi.org/10.1038/20715
  33. Ensina LF, Cusato-Ensina AP, Cardona R. 2019. Advances in the pathogenesis representing definite outcomes in chronic urticaria. Curr. Opin. Allergy Clin. Immunol. 19: 193-197. https://doi.org/10.1097/ACI.0000000000000519
  34. Peters BA, Dominianni C, Shapiro JA, Church TR, Wu J, Miller G, et al. 2016. The gut microbiota in conventional and serrated precursors of colorectal cancer. Microobiome 4: 69. https://doi.org/10.1186/s40168-016-0218-6
  35. Terzic J, Grivennikov S, Karin E, Karin M. 2010. Inflammation and colon cancer. Gastroenterology 138: 2101-2114. https://doi.org/10.1053/j.gastro.2010.01.058
  36. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. 2012. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat. Rev. Microbiol. 10: 575-582. https://doi.org/10.1038/nrmicro2819
  37. Wang X, Zhang L, Wang Y, Liu X, Zhang H, Liu Y, et al. 2018. Gut microbiota dysbiosis is associated with Henoch-Schonlein Purpura in children. Int. Immunopharmacol. 58: 1-8. https://doi.org/10.1016/j.intimp.2018.03.003
  38. Kolkhir P, Borzova E, Grattan C, Asero R, Pogorelov D, Maurer M. 2017. Autoimmune comorbidity in chronic spontaneous urticaria: a systematic review. Autoimmun. Rev. 16: 1196-1208. https://doi.org/10.1016/j.autrev.2017.10.003
  39. Sugino KY, Paneth N, Comstock SS. 2019. Michigan cohorts to determine associations of maternal pre-pregnancy body mass index with pregnancy and infant gastrointestinal microbial communities: late pregnancy and early infancy. PLoS One 14: e213733.
  40. Pitta DW, Indugu N, Vecchiarelli B, Hennessy M, Baldin M, Harvatine KJ. 2020. Effect of 2-hydroxy-4-(methylthio) butanoate (HMTBa) supplementation on rumen bacterial populations in dairy cows when exposed to diets with risk for milk fat depression. J. Dairy Sci. 103: 2718-2730. https://doi.org/10.3168/jds.2019-17389
  41. Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. 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
  42. Polkowska-Pruszynska B, Gerkowicz A, Krasowska D. 2019. The gut microbiome alterations in allergic and inflammatory skin diseases - an update. J. Eur. Acad. Dermatol. Venereol. 34: 455-464. https://doi.org/10.1111/jdv.15951
  43. Pundir P, Liu R, Vasavda C, Serhan N, Limjunyawong N, Yee R, et al. 2019. A connective tissue mast-cell-specific receptor detects bacterial quorum-sensing molecules and mediates antibacterial immunity. Cell Host Microbe 26: 114-122. https://doi.org/10.1016/j.chom.2019.06.003

Cited by

  1. Abnormalities in Gut Microbiota and Metabolism in Patients With Chronic Spontaneous Urticaria vol.12, 2021, https://doi.org/10.3389/fimmu.2021.691304
  2. Salivary Microbiota Is Significantly Less Diverse in Patients with Chronic Spontaneous Urticaria Compared to Healthy Controls: Preliminary Results vol.11, pp.12, 2021, https://doi.org/10.3390/life11121329