Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED - A Pilot Study

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Hetemäki , I , Jian , C , Laakso , S M , Mäkitie , O , Pajari , A-M , Vos de , W M , Arstila , P & Salonen , A 2021 , ' Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED - A Pilot Study ' , Frontiers in Immunology , vol. 12 , 668219 . https://doi.org/10.3389/fimmu.2021.668219

Titel: Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED - A Pilot Study
Författare: Hetemäki, Iivo; Jian, Ching; Laakso, Saila Marita; Mäkitie, Outi; Pajari, Anne-Maria; Vos de, Willem Meindert; Arstila, Petteri; Salonen, Anne
Upphovmannens organisation: Department of Bacteriology and Immunology
de Vos & Salonen group
HUMI - Human Microbiome Research
CAMM - Research Program for Clinical and Molecular Metabolism
HUS Children and Adolescents
Clinicum
Lastentautien yksikkö
Children's Hospital
Department of Food and Nutrition
Willem Meindert Vos de / Principal Investigator
Research Programs Unit
Petteri Arstila / Principal Investigator
Datum: 2021-07
Språk: eng
Sidantal: 12
Tillhör serie: Frontiers in Immunology
ISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2021.668219
Permanenta länken (URI): http://hdl.handle.net/10138/334347
Abstrakt: Backgrounds and Aims: APECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients’ clinical phenotype and gastrointestinal symptoms. Methods: DNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined. Results: Analysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus, were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms. Conclusions: Gut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms.
Subject: ANTIBODIES
AUTOIMMUNITY
CANDIDA-ALBICANS COLONIZATION
DISEASE
MICROBIOME
atopobium
autoantibodies
autoimmunity
dysbiosis
faecalibacterium
gut microbiota
immune dysregulation
lps
3121 General medicine, internal medicine and other clinical medicine
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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