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

Broad Institute of MIT and Harvard, Cambridge, Mass; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Mass; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark. Department of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Broad Institute of MIT and Harvard, Cambridge, Mass; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Mass. Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany. Institute of Functional Genomics, University of Regensburg, Regensburg, Germany. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass. Department of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address: Annamari.Ranki@hus.fi. Broad Institute of MIT and Harvard, Cambridge, Mass; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Mass; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass. Electronic address: xavier@molbio.mgh.harvard.edu.

The Journal of allergy and clinical immunology. 2021;(3):876-888

Abstract

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 AIRE-controlled 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.

Methodological quality

Publication Type : Controlled Clinical Trial

Metadata

MeSH terms : Cytokines ; Probiotics