Oral microbiota in autoimmune polyendocrine syndrome type 1

Bruserud, Øyvind; Siddiqui, Huma; Marthinussen, Michaela Cuida; Chen, Tsute; Jönsson, Roland; Oftedal, Bergithe E.; Olsen, Ingar; Husebye, Eystein S.; Wolff, Anette S. B.

doi:10.1080/20002297.2018.1442986

Cited by 11 publications

(9 citation statements)

References 40 publications

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“…Indeed, the salivary microbiome of patients was significantly different from healthy controls (Figure 7) and showed higher diversity. The dysbiosis in APECED patients' oral cavity has been described in an earlier investigation with some overlaps in differentially abundant taxonomic units between the two studies, but also with discrepancies that can arise from various technical, analytical and biological differences between the two studies (57). Alterations in the microbiota could also be caused by medications, as well as Sjögren's-like syndrome, which is especially frequent among APECED patients in the United States (10).…”

Section: Discussionmentioning

confidence: 82%

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity

Kaleviste

Rühlemann²,

Kärner

et al. 2020

Front. Immunol.

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Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by recessive mutations in the AIRE gene. The hallmark of the disease is the production of highly neutralizing autoantibodies against type I interferons and IL-22. Considering the importance of IL-22 in maintaining mucosal barrier integrity and shaping its microbial community, we sought to study potential changes in the oral cavity in this model of human IL-22 paucity. We found that besides known Th22 cell deficiency, APECED patients have significantly fewer circulating MAIT cells with potential IL-22 secreting capacity. Saliva samples from APECED patients revealed local inflammation, the presence of autoantibodies against IFN-α and IL-22, and alterations in the oral microbiota. Moreover, gene expression data of buccal biopsy samples suggested impaired antimicrobial response and cell proliferation, both of which are processes regulated by IL-22. Our data complement the knowledge gained from mouse models and support the concept of IL-22 being a critical homeostatic cytokine in human mucosal sites.

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Section: Discussionmentioning

confidence: 82%

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity

Kaleviste

Rühlemann²,

Kärner

et al. 2020

Front. Immunol.

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“…This difference is most likely explained by the fact that our study has a larger sample size, BMI-matched healthy controls from the same age range as the patients, and a fecal DNA extraction method that efficiently captures both gram-positive and gram-negative gut commensals (13). Moreover, two small studies on the salivary microbiota from six and seven APECED patients with agematched controls found altered bacterial compositions in APECED patients' oral cavity, but their results are mixed and in part discrepant (31,32).…”

Section: Discussionmentioning

confidence: 88%

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

et al. 2021

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Backgrounds and AimsAPECED 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.MethodsDNA 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.ResultsAnalysis 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.ConclusionsGut 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.

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“…Second, some alterations of the PBC salivary microbiota differ from those of several autoimmune diseases. For example, compared with HC saliva, saliva of celiac disease patients ( 27 ) and rheumatoid arthritis patients ( 28 , 29 ) showed enriched Lactobacillus and Lactobacillus salivarius separately, which were not observed in the comparison between PBC patients and HCs; patients with rheumatic heart disease had enriched salivary Streptococcus and depleted salivary Prevotella and Veillonella , which were altered conversely in PBC patients ( 30 ); Bacteroidetes were enriched in PBC saliva but were depleted in the saliva of patients with autoimmune polyendocrine syndrome type-1 ( 31 ). Finally, compared with HCs, PBC patients exhibited depletion of salivary Lactobacillales, particularly Streptococcaceae , which was enriched in PBC faeces ( 3 , 4 ).…”

Section: Discussionmentioning

confidence: 99%

The Salivary Microbiota of Patients With Primary Biliary Cholangitis Is Distinctive and Pathogenic

Jiang

Chen

et al. 2021

Front. Immunol.

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The role of host-microbiota interactions in primary biliary cholangitis (PBC) has received increased attention. However, the impact of PBC on the oral microbiota and contribution of the oral microbiota to PBC are unclear. In this study, thirty-nine PBC patients without other diseases and 37 healthy controls (HCs) were enrolled and tested for liver functions and haematological variables. Saliva specimens were collected before and after brushing, microbiota was determined using 16S rDNA sequencing, metabolomics was profiled using Gas Chromatography-Mass Spectrometer (GC-MS), 80 cytokines were assayed using biochips, and inflammation inducibility was evaluated using OKF6 keratinocytes and THP-1 macrophages. Finally, the effect of ultrasonic scaling on PBC was estimated. Compared with HCs, PBC saliva had enriched taxa such as Bacteroidetes, Campylobacter, Prevotella and Veillonella and depleted taxa such as Enterococcaceae, Granulicatella, Rothia and Streptococcus. PBC saliva also had enriched sCD163, enriched metabolites such as 2-aminomalonic acid and 1-dodecanol, and depleted metabolites such as dodecanoic acid and propylene glycol. sCD163, 4-hydroxybenzeneacetic acid and 2-aminomalonic acid were significantly correlated with salivary cytokines, bacteria and metabolites. Salivary Veillonellaceae members, 2-aminomalonic acid, and sCD163 were positively correlated with liver function indicators such as serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PBC salivary microbes induced more soluble interleukin (IL)-6 receptor α (sIL-6Rα), sIL-6Rβ and tumour necrosis factor ligand superfamily (TNFSF)13B from OKF6 keratinocytes, and PBC salivary supernatant induced more IL-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine (C-C motif) ligand (CCL)13, C-X-C motif chemokine (CXC)L1 and CXCL16 from THP-1 macrophages. Toothbrushing significantly reduced the expression of inflammatory cytokines such as IL-1β, IL-8 and TNF-α and harmful metabolites such as cadaverine and putrescine in PBC but not HC saliva after P‐value correction. The levels of ALP and bilirubin in PBC serum were decreased after ultrasonic scaling. Together, PBC patients show significant alterations in their salivary microbiota, likely representing one cause and treatment target of oral inflammation and worsening liver functions.

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Oral microbiota in autoimmune polyendocrine syndrome type 1

Cited by 11 publications

References 40 publications

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity

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

The Salivary Microbiota of Patients With Primary Biliary Cholangitis Is Distinctive and Pathogenic

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