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Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED

OBJECTIVE: Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotoni...

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Autores principales: Naskali, Emmi, Dettmer, Katja, Oefner, Peter J, Pereira, Pedro A B, Krohn, Kai, Auvinen, Petri, Ranki, Annamari, Kluger, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365670/
https://www.ncbi.nlm.nih.gov/pubmed/30608907
http://dx.doi.org/10.1530/EC-18-0513
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author Naskali, Emmi
Dettmer, Katja
Oefner, Peter J
Pereira, Pedro A B
Krohn, Kai
Auvinen, Petri
Ranki, Annamari
Kluger, Nicolas
author_facet Naskali, Emmi
Dettmer, Katja
Oefner, Peter J
Pereira, Pedro A B
Krohn, Kai
Auvinen, Petri
Ranki, Annamari
Kluger, Nicolas
author_sort Naskali, Emmi
collection PubMed
description OBJECTIVE: Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotonin (5-HT) biosynthesis. DESIGN: We sought to determine the serum levels of 5-HT, tryptophan (Trp) metabolites and L-DOPA in 37 Finnish APECED patients and to correlate their abundance with the presence of TPH and AADC Aabs, GI dysfunction and depressive symptoms. We also performed an exploratory analysis of the gut microbiome. METHODS: Serum 5-HT, L-DOPA and Trp metabolite levels were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). TPH and AADC Aabs were measured by ELISA. Depression was assessed with a structured RBDI questionnaire. The V3–V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration. RESULTS: Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found. CONCLUSIONS: This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression. Hence, serum 5-HT, TPH1 and AADC Aabs should be determined in APECED patients presenting with GI symptoms.
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spelling pubmed-63656702019-02-11 Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED Naskali, Emmi Dettmer, Katja Oefner, Peter J Pereira, Pedro A B Krohn, Kai Auvinen, Petri Ranki, Annamari Kluger, Nicolas Endocr Connect Research OBJECTIVE: Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotonin (5-HT) biosynthesis. DESIGN: We sought to determine the serum levels of 5-HT, tryptophan (Trp) metabolites and L-DOPA in 37 Finnish APECED patients and to correlate their abundance with the presence of TPH and AADC Aabs, GI dysfunction and depressive symptoms. We also performed an exploratory analysis of the gut microbiome. METHODS: Serum 5-HT, L-DOPA and Trp metabolite levels were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). TPH and AADC Aabs were measured by ELISA. Depression was assessed with a structured RBDI questionnaire. The V3–V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration. RESULTS: Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found. CONCLUSIONS: This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression. Hence, serum 5-HT, TPH1 and AADC Aabs should be determined in APECED patients presenting with GI symptoms. Bioscientifica Ltd 2019-01-04 /pmc/articles/PMC6365670/ /pubmed/30608907 http://dx.doi.org/10.1530/EC-18-0513 Text en © 2019 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research
Naskali, Emmi
Dettmer, Katja
Oefner, Peter J
Pereira, Pedro A B
Krohn, Kai
Auvinen, Petri
Ranki, Annamari
Kluger, Nicolas
Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED
title Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED
title_full Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED
title_fullStr Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED
title_full_unstemmed Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED
title_short Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED
title_sort serotonin and tryptophan metabolites, autoantibodies and gut microbiome in apeced
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365670/
https://www.ncbi.nlm.nih.gov/pubmed/30608907
http://dx.doi.org/10.1530/EC-18-0513
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