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1.
Front Cell Infect Microbiol ; 13: 1166389, 2023.
Article in English | MEDLINE | ID: mdl-37180436

ABSTRACT

Introduction: Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. Method: From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. Results: The microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. Conclusion: In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.


Subject(s)
Bacteria , Microbiota , Nasal Cavity , Rhinitis, Allergic , Rhinitis , Humans , Male , Female , Young Adult , Adult , Rhinitis, Allergic/microbiology , Rhinitis/microbiology , Nasal Cavity/microbiology , Metagenome , Biodiversity , RNA, Ribosomal, 16S/analysis , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification
2.
Front Immunol ; 14: 1079154, 2023.
Article in English | MEDLINE | ID: mdl-37020561

ABSTRACT

Background: Allergic rhinoconjunctivitis (ARC) and allergic rhinitis (AR) are prevalent allergic diseases. People are becoming increasingly aware of the impact of microbial disorders on host immunity and allergic diseases. Studies have demonstrated an association between allergic diseases and the microbiome, but much remains unknown. We assessed changes in the conjunctival microbiome and nasal microbiome in patients with ARC or AR. Methods: Conjunctival swabs and nasal swabs were collected from each participant for 16S rRNA amplicon sequencing. Bacterial communities were analyzed. Results: Forty patients with ARC, 20 patients suffering from AR, and 34 healthy controls (HCs) were recruited. This study found the abundance of conjunctival microbiome in patients with ARC or AR was significantly lower than that in HCs. The diversity of conjunctival microbiome in patients with AR was significantly lower than those in the other two groups. There is no significant difference in abundance of nasal microbiome between the three groups. The diversities of nasal microbiome in patients with ARC or AR were significantly lower than that in HCs. We found significant differences in microbiota compositions in patients with ARC or AR compared with those in HCs. However, no significant difference in microbiota compositions was found between patients with ARC and patients with AR. Microbiome functions in the ARC group and AR group were also altered compared with HCs. Conclusions: We revealed changes in the composition and function of the conjunctival microbiome and nasal microbiome of patients with ARC or AR, which suggests that there is a relationship between allergic conditions and the local microbiome.


Subject(s)
Conjunctivitis , Microbiota , Rhinitis, Allergic , Humans , Dysbiosis , RNA, Ribosomal, 16S/genetics , Rhinitis, Allergic/microbiology , Nose
3.
Nat Microbiol ; 8(2): 218-230, 2023 02.
Article in English | MEDLINE | ID: mdl-36635572

ABSTRACT

Allergic rhinitis (AR)-commonly called hay fever-is a widespread condition that affects the quality of life of millions of people. The pathophysiology of AR remains incompletely understood. In particular, it is unclear whether members of the colonizing nasal microbiota contribute to AR. Here, using 16S ribosomal RNA sequencing, we show that the nasal microbiome of patients with AR (n = 55) shows distinct differences compared with that from healthy individuals (n = 105), including decreased heterogeneity and the increased abundance of one species, Streptococcus salivarius. Using ex vivo and in vivo models of AR, we demonstrate that this commensal bacterium contributes to AR development, promoting inflammatory cytokine release and morphological changes in the nasal epithelium that are characteristic of AR. Our data indicate that this is due to the ability of S. salivarius to adhere to the nasal epithelium under AR conditions. Our study indicates the potential of targeted antibacterial approaches for AR therapy.


Subject(s)
Microbiota , Rhinitis, Allergic , Streptococcus salivarius , Humans , Quality of Life , Rhinitis, Allergic/microbiology , Nasal Mucosa
4.
Front Cell Infect Microbiol ; 12: 841995, 2022.
Article in English | MEDLINE | ID: mdl-35310838

ABSTRACT

Perturbation of the microbiome has numerous associations with the phenotypes and progression in chronic airways disease. However, the differences in the nasal microbiome in asthma and allergic rhinitis (AR) have not been defined. We examined whether the nasal microbiome would vary among different comorbidities in asthma and AR and that those differences may be associated with the severity of asthma. Nasal lavage fluid was collected from 110 participants, including 20 healthy controls, 30 subjects with AR, 30 subjects with asthma and 30 subjects with combined asthma + AR. The Asthma Control Questionnaire (ACQ-7) was used to evaluate asthma control status. Using 16S rRNA bacterial gene sequencing, we analyzed nasal microbiome in patients with asthma, AR, combined asthma + AR, and healthy controls. Bacterial diversity was analyzed in corresponding with α diversity indices (Chao and Shannon index). Compared with healthy controls, the Chao index tended to be lower in subjects with AR (P = 0.001), asthma (P = 0.001), and combined asthma + AR (P = 0.001) when compared with healthy controls. Furthermore, the Shannon index was significantly lower in subjects with asthma (P = 0.013) and comorbid asthma with AR (P = 0.004) than the control subjects. Disparity in the structure and composition of nasal bacteria were also observed among the four groups. Furthermore, patients with combined asthma + AR and isolated asthma were divided into two groups according to the level of disease control: partially or well-controlled and uncontrolled asthma. The mean relative abundance observed in the groups mentioned the genera of Pseudoflavonifractor were dominated in patients with well and partially controlled disease, in both isolated asthma and combined asthma + AR. In subjects with uncontrolled asthma and combined asthma + AR, a lower evenness and richness (Shannon index, P = 0.040) was observed in nasal microbiome composition. Importantly, lower evenness and richness in the nasal microbiome may be associated with poor disease control in combined asthma + AR. This study showed the upper airway microbiome is associated with airway inflammation disorders and the level of asthma control.


Subject(s)
Asthma , Microbiota , Rhinitis, Allergic , Asthma/complications , Bacteria/genetics , Humans , Microbiota/genetics , RNA, Ribosomal, 16S/genetics , Rhinitis, Allergic/complications , Rhinitis, Allergic/microbiology
5.
Int J Mol Sci ; 22(9)2021 Apr 29.
Article in English | MEDLINE | ID: mdl-33947066

ABSTRACT

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.


Subject(s)
Microbiota , Nasal Cavity/microbiology , Nasal Mucosa/microbiology , Rhinitis/microbiology , Sinusitis/microbiology , Adult , Antigens, Bacterial/immunology , Child , Chronic Disease , Dysbiosis/immunology , Dysbiosis/microbiology , Humans , Metabolomics/methods , Nasal Cavity/immunology , Nasal Mucosa/immunology , Proteomics/methods , Rhinitis/immunology , Rhinitis, Allergic/immunology , Rhinitis, Allergic/microbiology , Sequence Analysis, DNA/methods , Sinusitis/immunology
6.
Hum Exp Toxicol ; 40(11): 2012-2021, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34018444

ABSTRACT

Children are susceptible to allergic rhinitis (caused by external allergens) accompanied by functional gastrointestinal disease, which seriously affects physical and mental health. Antihistamines and nasal spray hormones are commonly used in clinical treatment, but these drugs often have unsatisfactory efficacy and result in high recurrence rates. Therefore, understanding the pathogenesis of allergic rhinitis with functional gastrointestinal disease and seeking safer treatment and prevention methods is essential. Herein, molecular ecology and immunoassays were used to analyze correlations between pediatric allergic rhinitis with functional gastrointestinal disease and both the intestinal microbiota and gastrointestinal peptide levels. Fifty healthy children (healthy group) and 80 children with allergic rhinitis with functional gastrointestinal disease (case group: evenly divided into a control group (conventional drug therapy) and an intervention group (conventional drug therapy + glutamine+probiotics)), were enrolled. Bifidobacterium and Lactobacillus counts and the gastrin and motilin levels were lower in the case group than in the healthy group, whereas Enterobacter, yeast, and Enterococcus counts and the somatostatin, serotonin, and vasoactive intestinal peptide levels were higher. Post treatment, intestinal microbiota indices, gastrointestinal peptide levels, and intestinal barrier function were better in the intervention group than in the control group (p < 0.05). The intervention group had a significantly higher total therapeutic response rate (95.00%) than the control group (77.50%). The intestinal microbiota was closely associated with gastrointestinal peptide levels. Treatment with glutamine and probiotics regulated these levels, re-established balance in the intestinal microbiota, and restored intestinal barrier function.


Subject(s)
Gastrointestinal Diseases/drug therapy , Gastrointestinal Diseases/physiopathology , Gastrointestinal Microbiome/drug effects , Histamine Antagonists/therapeutic use , Probiotics/therapeutic use , Rhinitis, Allergic/drug therapy , Rhinitis, Allergic/microbiology , Rhinitis, Allergic/physiopathology , Female , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/microbiology , Humans , Infant , Male , Rhinitis, Allergic/complications
7.
Nutrients ; 13(4)2021 Apr 16.
Article in English | MEDLINE | ID: mdl-33923532

ABSTRACT

BACKGROUND: Probiotics may prevent the allergic response development due to their anti-inflammatory and immunomodulatory effects. The aim of this study is to determine if the prophylactic treatment with a mixture of Bifidobacterium animalis subsp. Lactis BB12 and Enterococcus faecium L3 would reduce symptoms and need for drug use in children with allergic rhinitis (AR). METHODS: The study included 250 children aged from 6 to 17 years, affected by AR. Patients were randomly assigned to the intervention group (150) or to the placebo group (100). Patients in the intervention group, in addition to conventional therapy (local corticosteroids and/or oral antihistamines), were treated in the 3 months preceding the onset of symptoms related to the presence of the allergen to which the children were most sensitized, with a daily oral administration of a probiotic mixture containing the Bifidobacterium animalis subsp. Lactis BB12 DSM 15954 and the Enterococcus faecium L3 LMG P-27496 strain. We used Nasal Symptoms Score (NSS) to evaluate AR severity before and after the treatment with probiotics or placebo. RESULTS: the patients in the intervention group had a significant reduction in their NSS after probiotic treatment (p-value = 2.2 × 10-10. Moreover, for the same group of patients, we obtained a significant reduction in the intake of pharmacological therapy. In particular, we obtained a reduction in the use of oral antihistamines (p-value = 2.2 × 10-16), local corticosteroids (p-value = 2.2 × 10-13), and of both drugs (p-value 1.5 × 10-15). CONCLUSIONS: When administered as a prophylactic treatment, a mixture of BB12 and L3 statistically decreased signs and symptoms of AR and reduced significantly the need of conventional therapy.


Subject(s)
Bifidobacterium animalis , Enterococcus faecium , Probiotics/administration & dosage , Rhinitis, Allergic/prevention & control , Adolescent , Child , Double-Blind Method , Female , Humans , Male , Prospective Studies , Rhinitis, Allergic/microbiology , Treatment Outcome
8.
Expert Rev Clin Immunol ; 17(2): 115-126, 2021 02.
Article in English | MEDLINE | ID: mdl-33428498

ABSTRACT

Introduction: A substantial number of patients worldwide are affected by allergies. Emerging evidence suggests that the individual microbial composition might contribute to the development of allergies or might even protect from allergic diseases.Areas covered: This review provides a detailed summary regarding available knowledge on the composition of a healthy human microbiome at allergy relevant body sites. It highlights factors influencing the microbiota composition. Furthermore, recent findings on the mutual interaction of the microbiota with the innate and adaptive immune system are reported. In the final part, this knowledge is combined to discuss microbial implications for food allergy, allergic asthma, allergic rhinitis, and skin allergies. Literature for this review was gathered by searching PubMed and Google Scholar databases between October and December 2020.Expert opinion: Due to the highly individual composition, it is currently not possible to define the characteristics of a site-specific microbiome in health and disease. Mainly effects of bacterial communities have been investigated, while fungal or viral influences are not yet well understood. The communication between microbial communities found in different organs impact on allergy development. Thus, a personalized approach is essential to beneficially influence these complex interactions and to modulate the host-specific microbiota in allergies.


Subject(s)
Hypersensitivity , Microbiota , Adaptive Immunity , Asthma/immunology , Asthma/microbiology , Dermatitis, Atopic/immunology , Dermatitis, Atopic/microbiology , Drug Hypersensitivity/immunology , Drug Hypersensitivity/microbiology , Food Hypersensitivity/immunology , Food Hypersensitivity/microbiology , Gastrointestinal Microbiome/immunology , Gastrointestinal Microbiome/physiology , Humans , Hypersensitivity/immunology , Hypersensitivity/microbiology , Immunity, Innate , Microbiota/immunology , Microbiota/physiology , Respiratory System/immunology , Respiratory System/microbiology , Rhinitis, Allergic/immunology , Rhinitis, Allergic/microbiology , Skin/immunology , Skin/microbiology
9.
Front Immunol ; 12: 771136, 2021.
Article in English | MEDLINE | ID: mdl-35069544

ABSTRACT

Allergic rhinitis (AR) is a common heterogeneous chronic disease with a high prevalence and a complex pathogenesis influenced by numerous factors, involving a combination of genetic and environmental factors. To gain insight into the pathogenesis of AR and to identity diagnostic biomarkers, we combined systems biology approach to analyze microbiome and serum composition. We collected inferior turbinate swabs and serum samples to study the microbiome and serum metabolome of 28 patients with allergic rhinitis and 15 healthy individuals. We sequenced the V3 and V4 regions of the 16S rDNA gene from the upper respiratory samples. Metabolomics was used to examine serum samples. Finally, we combined differential microbiota and differential metabolites to find potential biomarkers. We found no significant differences in diversity between the disease and control groups, but changes in the structure of the microbiota. Compared to the HC group, the AR group showed a significantly higher abundance of 1 phylum (Actinobacteria) and 7 genera (Klebsiella, Prevotella and Staphylococcus, etc.) and a significantly lower abundance of 1 genus (Pelomonas). Serum metabolomics revealed 26 different metabolites (Prostaglandin D2, 20-Hydroxy-leukotriene B4 and Linoleic acid, etc.) and 16 disrupted metabolic pathways (Linoleic acid metabolism, Arachidonic acid metabolism and Tryptophan metabolism, etc.). The combined respiratory microbiome and serum metabolomics datasets showed a degree of correlation reflecting the influence of the microbiome on metabolic activity. Our results show that microbiome and metabolomics analyses provide important candidate biomarkers, and in particular, differential genera in the microbiome have also been validated by random forest prediction models. Differential microbes and differential metabolites have the potential to be used as biomarkers for the diagnosis of allergic rhinitis.


Subject(s)
Metabolome/immunology , Microbiota/immunology , Respiratory System , Rhinitis, Allergic , Adolescent , Adult , Aged , Biomarkers/blood , Female , Humans , Male , Metabolomics , Middle Aged , Respiratory System/immunology , Respiratory System/microbiology , Rhinitis, Allergic/blood , Rhinitis, Allergic/immunology , Rhinitis, Allergic/microbiology
10.
Int J Med Sci ; 17(17): 2603-2610, 2020.
Article in English | MEDLINE | ID: mdl-33162788

ABSTRACT

Objective: Interleukin-17 (IL-17) C is a cytokine expressed by epithelial cells in response to bacterial stimulation. In contrast to other members of the IL-17 family of cytokines, IL-17C is upregulated early during infection, maintains integrity of the epithelial layer barrier, and mediates the innate immune response. We investigated the expression profile of IL-17C in pediatric adenoids. Methods: Pediatric adenoid tissues and lavage fluids were collected from a total of 38 subjects. The Limulus amebocyte lysate test and real-time PCR using Staphylococcus aureus primers were performed to evaluate bacterial contents in adenoids. Expression of IL-17RE in adenoids was analyzed using real-time polymerase chain reaction and western blot. The expression of IL-17C was evaluated by western blot and immunohistochemistry and compared between allergic rhinitis (AR) and control subjects. The levels of Hsp27, Hsp70, and IL-17C in adenoid lavage fluids were evaluated by enzyme-linked immunosorbent assay, and the correlation between these molecules was statistically analyzed. Results: The pediatric adenoids were found to be exposed to bacteria and had a normal flora comprising both gram-negative and -positive bacteria. IL-17RE, an IL-17C specific receptor, was highly expressed in the epithelium of adenoids. IL-17C was expressed in all evaluated adenoid tissue samples, irrespective of the allergic status of the patient. IL-17C secretion was detected in half of the adenoid lavage fluid samples and was associated with Hsp70 level. Conclusion: Our findings indicate the possible role of pediatric adenoids in innate immunity modulation via an innate immunity-associated cytokine.


Subject(s)
Adenoids/immunology , Immunity, Innate , Interleukin-17/metabolism , Rhinitis, Allergic/immunology , Adenoids/metabolism , Adenoids/microbiology , Adenoids/pathology , Child , Child, Preschool , Epithelial Cells , Female , Humans , Male , Receptors, Interleukin-17/metabolism , Rhinitis, Allergic/microbiology , Rhinitis, Allergic/pathology
12.
BMC Microbiol ; 20(1): 301, 2020 10 07.
Article in English | MEDLINE | ID: mdl-33028252

ABSTRACT

BACKGROUND: The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models. RESULTS: Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. CONCLUSION: Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.


Subject(s)
Immunity, Innate , Nasal Mucosa/immunology , Rhinitis, Allergic/immunology , Staphylococcus aureus/immunology , Staphylococcus epidermidis/immunology , Symbiosis/immunology , Animals , Corynebacterium/growth & development , Cytokines/genetics , Cytokines/immunology , Disease Models, Animal , Enterobacter aerogenes/growth & development , Epithelial Cells/immunology , Epithelial Cells/microbiology , Female , Gene Expression , Humans , Interleukin-33/genetics , Interleukin-33/immunology , Mice, Inbred BALB C , Micrococcus luteus/growth & development , Mucus/immunology , Mucus/microbiology , Nasal Mucosa/microbiology , Ovalbumin/administration & dosage , Primary Cell Culture , RNA, Messenger/genetics , RNA, Messenger/immunology , Rhinitis, Allergic/chemically induced , Rhinitis, Allergic/microbiology , Rhinitis, Allergic/pathology , Staphylococcus aureus/growth & development , Staphylococcus epidermidis/growth & development
13.
Microb Cell Fact ; 19(1): 171, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32873292

ABSTRACT

BACKGROUND: Although recent studies have indicated that intestinal microbiota dweller are involved in the pathogenesis of allergy rhinitis (AR), the influence of gut microbiota on AR adult has not been fully elucidated yet. Hence, we carried out this study to uncover the distinctive bacterial taxa that differentiate allergy rhinitis patients from healthy individuals. Feces samples from thirty three AR patients and thirty one healthy individuals were analyzed by 16S rRNA gene sequencing. RESULTS: Results showed that the bacterial diversity in AR group was significantly higher than that of the non-AR group. Bacterial communities between AR and non-AR group were significantly differentiated as revealed by Principal coordinates analysis (PCoA) and the variation within non-AR were higher than that of the counterpart. Firmicutes, Fusobacteria, Actinobacteria, Cyanobacteria and Chloroflexi were the significantly differed phyla taxa and the top significantly distinguished bacterial genus included Prevotella_9, Phascolarctobacterium, Roseburia, Megamonas, Alistipes, Lachnoclostridium and Fusobacterium. The higher network complexity in AR group were dominated by taxa belonging to Firmicutes. The predicted function, alpha linolenic acid metabolism and bacterial invasion of epithelial cells pathway were higher in non-AR group while gonadotropin-releasing hormone (GnRH) signaling pathway, Fc γ-R mediated phagocytosis and endocytosis were higher in AR patients. Although the bacterial diversity between moderate and severe AR patients showed no significant difference, the significant correlation between featured genus and total nasal symptom score or rhinoconjunctivitis quality of life questionnaire, such as Butyricicoccus and Eisenbergiella, revealed the potential to intervene the AR status by means of gut microbiota. CONCLUSIONS: In conclusion, patients with allergy rhinitis had distinguished gut microbiota characteritics in comparison with healthy controls. The results suggest that gut microbiota might play crucial roles in influencing the course and different symptoms of AR. Trial registration ChiCTR, ChiCTR1900028613. Registered 29 December 2019, https://www.chictr.org.cn/showproj.aspx?proj=47650 .


Subject(s)
Biodiversity , Feces/microbiology , Gastrointestinal Microbiome , Rhinitis, Allergic/microbiology , Adult , China/epidemiology , Female , Genome, Bacterial , Humans , Male , Metagenome , Quality of Life , RNA, Ribosomal, 16S , Severity of Illness Index , Surveys and Questionnaires , Young Adult
14.
J Allergy Clin Immunol ; 146(6): 1358-1366, 2020 12.
Article in English | MEDLINE | ID: mdl-32693091

ABSTRACT

BACKGROUND: The upper airways present a barrier to inhaled allergens and microbes, which alter immune responses and subsequent risk for diseases, such as allergic rhinitis (AR). OBJECTIVE: We tested the hypothesis that early-life microbial exposures leave a lasting signature in DNA methylation that ultimately influences the development of AR in children. METHODS: We studied upper airway microbiota at 1 week, 1 month, and 3 months of life, and measured DNA methylation and gene expression profiles in upper airway mucosal cells and assessed AR at age 6 years in children in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort. RESULTS: We identified 956 AR-associated differentially methylated CpGs in upper airway mucosal cells at age 6 years, 792 of which formed 3 modules of correlated differentially methylated CpGs. The eigenvector of 1 module was correlated with the expression of genes enriched for lysosome and bacterial invasion of epithelial cell pathways. Early-life microbial diversity was lower at 1 week (richness P = .0079) in children with AR at age 6 years, and reduced diversity at 1 week was also correlated with the same module's eigenvector (ρ = -0.25; P = 3.3 × 10-5). We show that the effect of microbiota richness at 1 week on risk for AR at age 6 years was mediated in part by the epigenetic signature of this module. CONCLUSIONS: Our results suggest that upper airway microbial composition in infancy contributes to the development of AR during childhood, and this trajectory is mediated, at least in part, through altered DNA methylation patterns in upper airway mucosal cells.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Microbiota , Nose/microbiology , Rhinitis, Allergic , Child , Female , Humans , Infant , Infant, Newborn , Male , Prospective Studies , Rhinitis, Allergic/metabolism , Rhinitis, Allergic/microbiology
15.
Ann Allergy Asthma Immunol ; 125(5): 517-527, 2020 11.
Article in English | MEDLINE | ID: mdl-32454094

ABSTRACT

OBJECTIVE: Our understanding of the origin of allergic diseases has increased in recent years, highlighting the importance of microbial dysbiosis and epithelial barrier dysfunction in affected tissues. Exploring the microbial-epithelial-immune crosstalk underlying the mechanisms of allergic diseases will allow the development of novel prevention and treatment strategies for allergic diseases. DATA SOURCES: This review summarizes the recent advances in microbial, epithelial, and immune interactions in atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma. STUDY SELECTIONS: We performed a literature search, identifying relevant recent primary articles and review articles. RESULTS: Dynamic crosstalk between the environmental factors and microbial, epithelial, and immune cells in the development of atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma underlies the pathogenesis of these diseases. There is substantial evidence in the literature suggesting that environmental factors directly affect barrier function of the epithelium. In addition, T-helper 2 (TH2) cells, type 2 innate lymphoid cells, and their cytokine interleukin 13 (IL-13) damage skin and lung barriers. The effects of environmental factors may at least in part be mediated by epigenetic mechanisms. Histone deacetylase activation by type 2 immune response has a major effect on leaky barriers and blocking of histone deacetylase activity corrects the defective barrier in human air-liquid interface cultures and mouse models of allergic asthma with rhinitis. We also present and discuss a novel device to detect and monitor skin barrier dysfunction, which provides an opportunity to rapidly and robustly assess disease severity. CONCLUSION: A complex interplay between environmental factors, epithelium, and the immune system is involved in the development of systemic allergic diseases.


Subject(s)
Cytokines/immunology , Epithelium/immunology , Hypersensitivity/immunology , Hypersensitivity/microbiology , Immune System/microbiology , Animals , Asthma/immunology , Asthma/microbiology , Dermatitis, Atopic/immunology , Dermatitis, Atopic/microbiology , Disease Models, Animal , Epithelium/microbiology , Humans , Immunity, Innate , Lymphocytes/immunology , Mice , Rhinitis, Allergic/immunology , Rhinitis, Allergic/microbiology
16.
Laryngoscope ; 130(12): E882-E888, 2020 12.
Article in English | MEDLINE | ID: mdl-32181890

ABSTRACT

OBJECTIVES/HYPOTHESIS: Recent research has examined the nasal microbiome in rhinosinusitis and nondiseased states. Given immunologic alterations in allergic rhinitis (AR) and after allergen immunotherapy (IT), we evaluated the nasal microbiome in these conditions. STUDY DESIGN: Cross-sectional comparison. METHODS: In this cross-sectional study, nasal swabs for microbiome analysis were collected from three patient groups: IT-naïve AR patients, AR patients undergoing IT for greater than 12 months, and a control group without sinonasal inflammatory disease. RESULTS: Nasal swabs were successfully collected for 14 IT-naïve AR patients, 20 post-IT patients, and 17 controls. The α diversity showed a statistical difference in evenness but not in richness amongst samples, whereas the ß-diversity was significantly different between groups. Corynebacterium and Staphylococcus were the most prevalent bacteria across all groups. CONCLUSIONS: ß-diversity was found to be significantly different across the three groups, but the AR groups were found to be more similar to each other than to the controls. Although there is symptomatic improvement in the AR group undergoing IT, the microbiome does not appear to transition to a healthy microbiome composition. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.


Subject(s)
Bacteria/isolation & purification , Desensitization, Immunologic , Microbiota , Nose/microbiology , Rhinitis, Allergic/microbiology , Rhinitis, Allergic/therapy , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Rhinitis, Allergic/immunology , Young Adult
18.
Eur Arch Otorhinolaryngol ; 277(1): 121-128, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31552526

ABSTRACT

PURPOSE: Allergic fungal rhinosinusitis (AFRS) is a common disorder with a high prevalence and a very high incidence of recurrence. Management includes surgery and medical treatment in the form of local and/or systemic steroids. However, some cases are resistant to the action of steroids and further treatment is warranted. Being an immune-mediated disorder, targeting IgE seems a logical step. Immunotherapy drugs acting on the IgE (e.g. omalizumab) can modify the clinical course of the disease. This study aimed at evaluating the effect of omalizumab on the clinical course of patients undergoing surgery for AFRS. MATERIALS AND METHODS: This is a two-arm prospective, randomized, single blind clinical trial among patients with AFRS. Twenty patients were included and randomly divided into two groups: Group A; 10 patients received a single subcutaneous injection of omalizumab (Xolair ' Novartis) (150 mg) 2 weeks postoperatively. Group B: 10 patients received local steroids nasal sprays (budesonide or mometasone furoate, 100 µg twice daily for 6 months, starting 2 weeks postoperatively. All patients underwent history, examination, CT scan and IgE level estimation and were submitted to endoscopic sinus surgery. They were evaluated at 4 weeks interval for 6 months. RESULTS: In both groups there were highly significant differences between pre/post-operative SNOT-20 scores, TNSS scores, total IgE level and Philpott-Javer staging scores. Comparison between the two study groups at 24 weeks showed a highly significant difference (p = 0.001) between post-operative SNOT 20 and TNSS scores in favour of group A. There was no statistically significant difference between the two study groups as regarding postoperative total IgE or Philpott-Javer scores. There were two recurrences in both arms, but no significant side effects. DISCUSSION: We compared a single post operative injection of omalizumab with twice daily intranasal steroid spray for 6 months. Both treatments were effective, but the omalizumab group showed a more significant clinical and endoscopic response. There were no significant side effects in both arms. This novel approach used a single low dose injection of omalizumab increased the compliance of the patients with minimal complications. Longer follow-up of the patients is ongoing to determine the optimal time for re-injection. The only downside was the higher cost of omalizumab compared to that of local steroids.


Subject(s)
Glucocorticoids/administration & dosage , Mycoses/drug therapy , Omalizumab/administration & dosage , Rhinitis, Allergic/drug therapy , Sinusitis/drug therapy , Administration, Intranasal , Adolescent , Adult , Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/therapeutic use , Budesonide/administration & dosage , Budesonide/immunology , Budesonide/therapeutic use , Chronic Disease , Endoscopy , Female , Glucocorticoids/therapeutic use , Health Status Indicators , Humans , Immunoglobulin E/immunology , Injections, Subcutaneous , Male , Mometasone Furoate/administration & dosage , Mometasone Furoate/therapeutic use , Mycoses/immunology , Mycoses/microbiology , Mycoses/surgery , Nasal Polyps/drug therapy , Nasal Polyps/immunology , Nasal Polyps/surgery , Nasal Sprays , Omalizumab/therapeutic use , Prospective Studies , Rhinitis, Allergic/immunology , Rhinitis, Allergic/microbiology , Rhinitis, Allergic/surgery , Single-Blind Method , Sinusitis/immunology , Sinusitis/microbiology , Sinusitis/surgery , Tomography, X-Ray Computed , Young Adult
19.
Am J Otolaryngol ; 41(1): 102301, 2020.
Article in English | MEDLINE | ID: mdl-31732306

ABSTRACT

PURPOSE: Allergic fungal rhinosinusitis (AFRS) forms a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) that is mainly characterized by eosinophilic nasal polyps, allergic mucin detected in the sinuses at surgery, and specific features on computerized tomography. Which biological markers predict disease recurrence in AFRS is still not clear, and the role of blood inflammatory cells in predicting recurrent polyps after surgery has yet to be investigated. The aim of this study was to newly investigate the prognostic role (in terms of recurrence rate) of preoperative blood eosinophil and basophil levels in AFRS. MATERIALS AND METHODS: A consecutive series of 17 adult patients who underwent endoscopic sinus surgery for AFRS was retrospectively assessed. RESULTS: Sinonasal polyps recurred in 7 of 17 patients. Considering the whole cohort, a significant positive correlation emerged between blood eosinophil and basophil counts, but not between blood and tissue eosinophil counts. Statistical analysis found significantly higher blood eosinophil and basophil levels in AFRS patients who relapsed than in those who did not. CONCLUSIONS: Considering the current difficulty of identifying more effective, personalized approaches to postoperative disease management in AFRS, our preliminary data support the impression that blood eosinophil and basophil levels warrant testing in further prospective and larger (preferably multi-institutional) investigations as part of the preoperative work-up for patients with AFRS in order to administer dedicated postoperative medical treatments for patients at higher risk of relapse.


Subject(s)
Basophils , Eosinophils , Mycoses/blood , Mycoses/microbiology , Rhinitis, Allergic/blood , Rhinitis, Allergic/microbiology , Sinusitis/blood , Sinusitis/microbiology , Adult , Chronic Disease , Endoscopy , Female , Humans , Male , Middle Aged , Mucins/analysis , Mycoses/diagnostic imaging , Mycoses/surgery , Nasal Polyps/blood , Nasal Polyps/diagnostic imaging , Nasal Polyps/microbiology , Nasal Polyps/surgery , Prognosis , Recurrence , Retrospective Studies , Rhinitis, Allergic/diagnostic imaging , Rhinitis, Allergic/surgery , Sinusitis/diagnostic imaging , Sinusitis/surgery , Tomography, X-Ray Computed
20.
Curr Opin Allergy Clin Immunol ; 20(1): 30-35, 2020 02.
Article in English | MEDLINE | ID: mdl-31789894

ABSTRACT

PURPOSE OF REVIEW: The prevalence of chronic upper airway inflammatory diseases such as allergic rhinitis and chronic rhinosinusitis (CRS) is increasing markedly posing a potential health threat globally. The involvement of the upper respiratory microbiota in chronic inflammatory diseases of the upper airways has been of considerable interest. The purpose of this review is to understand the characteristics of upper respiratory microbiota in both healthy and chronic inflammatory diseases of the upper airways like allergic rhinitis and CRS and to know the potential role of interventions with probiotics. RECENT FINDINGS: We present here the studies on the nasal microbiota in healthy infants, allergic rhinitis, and CRS. The results demonstrate that there are stable and unstable profiles of microbiota during infancy. Decreased diversity or an imbalance of the microbial composition could be an important factor in the development of both allergic rhinitis and CRS. We also discuss here several recent animal and human studies that demonstrate the effect of probiotics in allergic rhinitis and chronic rhinosinusitis. Results from human studies (clinical trials) have demonstrated that probiotics may be effective for allergic rhinitis, but there are no consistent results in human CRS trials. SUMMARY: Several strains of probiotics revealed potential efficacy for allergic rhinitis but not for CRS. Large clinical trials are essential to establish robust data on probiotics for chronic inflammatory upper airways diseases like allergic rhinitis and CRS.


Subject(s)
Inflammation/microbiology , Microbiota/immunology , Respiratory System/microbiology , Rhinitis, Allergic/microbiology , Rhinitis/microbiology , Animals , Chronic Disease , Clinical Trials as Topic , Humans , Probiotics/therapeutic use , Respiratory System/immunology , Rhinitis/immunology , Rhinitis/therapy , Rhinitis, Allergic/immunology , Rhinitis, Allergic/therapy
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