The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients.
The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients.
复制标题
肠道微生物群和代谢组与免疫抑制的炎症性肠病患者中COVID-19疫苗诱导的抗体应答减少相关。
DOI：
10.1016/j.ebiom.2022.104430
复制
发表时间：
2023-02
期刊：
影响因子：
11.1
通讯作者：
Powell, Nick
中科院分区：
文献类型：
--
作者：
Alexander, James L.;Mullish, Benjamin H.;Danckert, Nathan P.;Liu, Zhigang;Olbei, Marton L.;Saifuddin, Aamir;Torkizadeh, Melissa;Ibraheim, Hajir;Blanco, Jesus Miguens;Roberts, Lauren A.;Bewshea, Claire M.;Nice, Rachel;Lin, Simeng;Prabhudev, Hemanth;Sands, Caroline;Horneffer-van der Sluis, Verena;Lewis, Matthew;Sebastian, Shaji;Lees, Charlie W.;Teare, Julian P.;Hart, Ailsa;Goodhand, James R.;Kennedy, Nicholas A.;Korcsmaros, Tamas;Marchesi, Julian R.;Ahmad, Tariq;Powell, Nick
关键词：
接受抗 TNF 治疗的炎症性肠病 (IBD) 患者对 SARS-CoV-2 疫苗接种表现出体液免疫反应减弱。 IBD 中受到干扰的肠道微生物群及其功能代谢输出在塑造宿主免疫反应中发挥着重要作用。我们探讨了肠道微生物群和代谢组是否可以解释免疫抑制 IBD 患者抗 SARS-CoV-2 疫苗接种反应的变化。在 CLARITY-IBD 研究中，前瞻性地从英夫利昔单抗治疗的 IBD 患者中收集了粪便和血清样本，这些患者正在接受 SARS-CoV-2 疫苗接种。在接种两剂 ChAdOx1 nCoV-19 或 BNT162b2 疫苗后测量抗体反应。患者被分类为反应高于或低于更广泛的 CLARITY-IBD 队列的几何平均值。对粪便样本进行了 16S rRNA 基因扩增子测序、核磁共振 (NMR) 光谱分析以及超高效液相色谱质谱 (UHPLC-MS) 胆汁酸分析。进行单变量、多变量和相关分析以确定疫苗接种反应的肠道微生物和代谢组学预测因子。招募了 43 名接受英夫利昔单抗治疗的 IBD 患者（30 名克罗恩病患者、12 名溃疡性结肠炎患者、1 名 IBD 未分类患者；26 名患者同时接受硫嘌呤治疗）。 8 名患者有先前感染 SARS-CoV-2 的证据。 17 名患者 (39.5%) 的血清学反应低于几何平均值。低于平均水平的反应者肠道微生物群多样性较低 (p = 0.037)。嗜胆菌丰度与较好的血清学反应相关，而链球菌与较差的反应相关。高于和低于平均水平的反应者的粪便代谢组是不同的（OPLS-DA R2X 0.25、R2Y 0.26、Q2 0.15；CV-ANOVA p = 0.038）。三甲胺、异丁酸盐和 omega-鼠胆酸与较好的反应相关，而琥珀酸盐、苯丙氨酸、牛磺石胆酸盐和牛磺脱氧胆酸盐与较差的反应相关。我们的数据表明，免疫功能低下患者的肠道微生物群与对 SARS-CoV-2 疫苗接种的不同血清学反应之间存在关联。包括三甲胺在内的微生物代谢物可能在减轻抗 TNF 诱导的免疫反应减弱方面发挥重要作用。 JLA 是 NIHR 学术临床讲座 (CL-2019-21-502) 的获得者，由 和 资助。 BHM 是 NIHR 学术临床讲师 (CL-2019-21-002) 的获得者。伦敦帝国理工学院消化疾病科接受总部位于 和 的 (BRC) 的财政和基础设施支持。代谢组学研究在伦敦帝国理工学院 MRC-NIHR 国家表型组中心进行；这项工作得到了 (MRC)、(NIHR)（拨款号 MC_PC_12025）的支持，基础设施支持由 (BRC) 提供。 NIHR 埃克塞特临床研究机构是埃克塞特大学医学院医学与健康学院与皇家德文郡和埃克塞特 NHS 基金会信托基金之间的合作伙伴关系。该项目得到 (NIHR) 埃克塞特临床研究机构的支持。所表达的观点仅代表作者的观点，并不一定代表 NIHR 或英国卫生和社会保障部的观点。
Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by and . BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the (BRC) based at and . Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the (MRC), the (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.
登录
查看更多内容
影响因子：
3.6
作者：
Bjerrum, Jacob Tveiten;Wang, Yulan;Hao, Fuhua;Coskun, Mehmet;Ludwig, Christian;Guenther, Ulrich;Nielsen, Ole Haagen
通讯作者：
Nielsen, Ole Haagen
影响因子：
64.8
作者：
Devkota, Suzanne;Wang, Yunwei;Musch, Mark W.;Leone, Vanessa;Fehlner-Peach, Hannah;Nadimpalli, Anuradha;Antonopoulos, Dionysios A.;Jabri, Bana;Chang, Eugene B.
通讯作者：
Chang, Eugene B.
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
35.7
作者：
Alexander, James L.;Liu, Zhigang;Sandoval, Diana Munoz;Reynolds, Catherine;Ibraheim, Hajir;Anandabaskaran, Sulak;Saifuddin, Aamir;Seoane, Rocio Castro;Anand, Nikhil;Nice, Rachel;Bewshea, Claire;D'Mello, Andrea;Constable, Laura;Jones, Gareth R.;Balarajah, Sharmili;Fiorentino, Francesca;Sebastian, Shaji;Irving, Peter M.;Hicks, Lucy C.;Williams, Horace R. T.;Kent, Alexandra J.;Linger, Rachel;Parkes, Miles;Kok, Klaartje;Patel, Kamal V.;Teare, Julian P.;Altmann, Daniel M.;Goodhand, James R.;Hart, Ailsa L.;Lees, Charlie W.;Boyton, Rosemary J.;Kennedy, Nicholas A.;Ahmad, Tariq;Powell, Nick
通讯作者：
Powell, Nick
影响因子：
15.5
作者：
Davis, Nicole M;Proctor, Diana M;Callahan, Benjamin J
通讯作者：
Callahan, Benjamin J