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. 2019 Jan 1;8(1):69-77.
doi: 10.1530/EC-18-0513.

Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED

Emmi Naskali  1 , Katja Dettmer  2 , Peter J Oefner  2 , Pedro A B Pereira  3 , Kai Krohn  4 , Petri Auvinen  3 , Annamari Ranki  1 , Nicolas Kluger  1
Affiliations

Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED

Emmi Naskali et al. Endocr Connect. .

Abstract

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.

Keywords: APECED; Paneth cells; constipation; diarrhea; entero-endrocrine cells; serotonin.

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Figures

Figure 1
Figure 1
Serum serotonin levels (nmol/L) in relation to circulating TPH-1 and AADC Aabs. The line represents the mean value of serum serotonin for each patient group and healthy control persons.
Figure 2
Figure 2
Serum metabolite concentrations (nmol/L) according to the presence of severe constipation.
Figure 3
Figure 3
Stool microbiome alpha diversity indices for control persons and APECED subjects. Based on non-rarefied count data at the OTU level.
Figure 4
Figure 4
Taxon relative abundances (%) of the control and APECED groups. The 20 most common genera in the entire data set are explicitly shown.
Figure 5
Figure 5
Relative abundances (%) of the genus Escherichia/Shigella for control persons and APECED subjects.
See this image and copyright information in PMC

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