Cytokine-specific autoantibodies shape the gut microbiome in autoimmune polyendocrine syndrome type 1

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:148

Article

Petersen, Anders O.^1,2,3  Jokinen, Martta^4,5  Plichta, Damian R.^1,2  Liebisch, Gerhard⁶  Gronwald, Wolfram⁷  Dettmer, Katja⁷  Oefner, Peter J.⁷  Vlamakis, Hera^1,2  Chung, Daniel C.⁸  Ranki, Annamari^4,5  Xavier, Ramnik J.^{1,2,8,9,10,11} 

[1] Broad Inst & Harvard, Cambridge, MA 02142 USA

[2] MIT, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA

[3] Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark

[4] Univ Helsinki, Dept Dermatol & Allergol, Helsinki, Finland

[5] Helsinki Univ Hosp, Helsinki, Finland

[6] Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany

[7] Univ Regensburg, Inst Funct Gen, Regensburg, Germany

[8] Harvard Med Sch, Div Gastroenterol, Boston, MA 02115 USA

[9] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[10] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[11] Harvard Med Sch, Boston, MA 02115 USA

关键词: APS-1;    APECED;    autoimmunity;    autoantibody;    cytokine;    chemokine;    microbiome;    Lactobacillus rhamnosus GG;    tryptophan;    GABA;   

DOI  :  10.1016/j.jaci.2021.03.025

来源: Elsevier

【 摘 要 】

Background: Gastrointestinal dysfunction is a frequent and disabling manifestation of autoimmune polyendocrine syndrome type 1 (APS-1), a rare monogenic multiorgan autoimmune disease caused by the loss of central AIREcontrolled immune tolerance. Objectives: This study aimed to understand the role of the gut microbiome in APS-1 symptoms and potentially alleviate common gastrointestinal symptoms by probiotic intervention. Methods: This study characterized the fecal microbiomes of 28 patients with APS-1 and searched for associations with gastrointestinal symptoms, circulating anti-cytokine autoantibodies, and tryptophan-related metabolites. Additionally, daily doses of the probiotic Lactobacillus rhamnosus GG were administered for 3 months. Results: Of 581 metagenomic operational taxonomic units (mOTUs) characterized in total, 14 were significantly associated with patients with APS-1 compared with healthy controls, with 6 mOTUs depleted and 8 enriched in patients with APS-1. Four overabundant mOTUs were significantly associated with severity of constipation. Phylogenetically conserved microbial associations with autoantibodies against cytokines were observed. After the 3-month intervention with the probiotic L rhamnosus GG, a subset of gastrointestinal symptoms were alleviated. L rhamnosus GG abundance was increased postintervention and corresponded with decreased abundances of Alistipes onderdonkii and Collinsella aerofaciens, 2 species positively associated with severity of diarrhea in patients with APS-1. Conclusions: The APS-1 microbiome correlates with several APS-1 symptoms, some of which are alleviated after a 3-month L rhamnosus GG intervention. Autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria. (J Allergy Clin Immunol 2021;148:876-88.)

【 授权许可】

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