Increased diversity of gut microbiota during active oral immunotherapy in peanut‐allergic adults

He, Ziyuan; Vadali, VL Gouri; Szabady, Rose L.; Zhang, Wenming; Norman, Jason; Roberts, Bruce; Tibshirani, Robert; Desai, Manisha; Chinthrajah, R. Sharon; Galli, Stephen J.; Andorf, Sandra

doi:10.1111/all.14540

Cited by 18 publications

(13 citation statements)

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“…Additional cell types such as dendritic cells, ILCs, Tfh cells and MDSCs should be explored in the context of food allergy and immunotherapy. The microbiome 97 and other local factors in the gut may also impact the response to OIT. Future studies are needed to better elucidate the complex immunologic changes that occur during OIT, particularly those that are associated with SU.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of oral immunotherapy

Barshow

Kulis

Burks

et al. 2021

Clin Experimental Allergy

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Section: Discussionmentioning

confidence: 99%

Mechanisms of oral immunotherapy

Barshow

Kulis

Burks

et al. 2021

Clin Experimental Allergy

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“…Increased microbial gut diversity has been suggested to reflect an immunomodulatory effect of OIT on the host immune system in successful desensitization [ 35 ]. A recent publication that retrospectively investigated stool samples collected from seven adult participants who received POIT, reported a significant increase in alpha diversity after treatment, but no change in beta diversity [ 35 ]. Similarly, in our cohort, beta diversity did not show any significant difference in either oral or gut microbiome between baseline and end of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Bifidobacteria and their metabolites have been shown to induce peripheral regulatory T (Treg) cells that control inflammation and promote tolerance in murine models and infant studies [ 45 , 46 , 48 , 49 ]. Another recent study reported overrepresentation of five Clostridial species, one Firmicutes bacterium, and one Bacteroides species in stool samples of adult subjects after POIT compared with baseline [ 35 ]. In contrast, Firmicutes and Bacteroidetes phyla were underrepresented in our pediatric cohort.…”

Section: Discussionmentioning

confidence: 99%

Insights into Microbiome and Metabolic Signatures of Children Undergoing Peanut Oral Immunotherapy

et al. 2022

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Background: Peanut oral immunotherapy has emerged as a novel, active management approach for peanut-allergic sufferers, but limited data exist currently on the role of the microbiome in successful desensitization. Objective: We examined the oral and gut microbiome in a cohort of 17 children undergoing peanut oral immunotherapy with the aim to identify the microbiome signatures associated with successful desensitization. We also set out to characterize their fecal metabolic profiles after successful therapy. Methods: Participants gradually built up their daily dose from 2 mg (starting dose) to 300 mg (maintenance dose) within approximately 40 weeks. We collected a buccal and stool specimen from each subject at two different time points: at baseline and post-therapy (1 month after reaching maintenance). The oral (buccal) and gut (fecal) microbiome was characterized based on sequencing of 16S rRNA gene amplicons with Illumina MiSeq. Fecal short chain fatty acid levels were measured using liquid chromatography-tandem mass spectrometry. Results: We report increased alpha diversity of the oral microbiome post-therapy and have also identified a significant increase in the relative abundance of oral Actinobacteria, associated with the desensitized state. However, the baseline gut microbiome did not differ from the post-therapy. Additionally, fecal short chain fatty acids increased after therapy, but not significantly. Conclusion: Our research adds to the limited current knowledge on microbiome and metabolic signatures in pediatric patients completing oral immunotherapy. Post-therapy increased trends of fecal fatty acid levels support a role in modulating the allergic response and potentially exerting protective and anti-inflammatory effects alongside successful desensitization. A better understanding of the microbiome-related mechanisms underlying desensitization may allow development of smarter therapeutic approaches in the near future. Clinical implication: The oral microbiome composition is altered following successful peanut oral immunotherapy, with a significant increase in alpha diversity and the relative abundance of phylum Actinobacteria. Capsule summary: Significant microbiome changes in children completing peanut immunotherapy include increase in alpha-diversity and overrepresentation of Actinobacteria in the oral microbiome, and increased trends for fecal short chain fatty acids, suggesting a protective effect against the allergic response.

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“…The adaptive immune response is influenced by microbial interactions with secreted IgA ( 120 ), together with lower richness and lower local species diversity (alpha diversity), accompanied by a dysbiosis of commensal strains ( 92 , 93 ). A previous study demonstrated that peanut allergy is marked by higher Bacteroidales, especially Bacteroides fragilis and reduced Clostridiales abundance ( 92 ).…”

Section: Emerging Omic-areas For Clinical Endotypingmentioning

confidence: 99%

“…A previous study demonstrated that peanut allergy is marked by higher Bacteroidales, especially Bacteroides fragilis and reduced Clostridiales abundance (92). Low threshold reactivity to peanut has been connected to an increase in Clostridium sp, Oscillosiraceae sp, Lachnospiraceae sp, Ruminococcaceae sp, Frimicutes sp, and Bacteroides sp (91)(92)(93). At which gastrointestinal sites immune dysregulation and allergic sensitization might develop is unexplored.…”

Section: Microbiomics and Gut Tissue Typingmentioning

confidence: 99%

IgE-Mediated Peanut Allergy: Current and Novel Predictive Biomarkers for Clinical Phenotypes Using Multi-Omics Approaches

et al. 2021

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Food allergy is a collective term for several immune-mediated responses to food. IgE-mediated food allergy is the best-known subtype. The patients present with a marked diversity of clinical profiles including symptomatic manifestations, threshold reactivity and reaction kinetics. In-vitro predictors of these clinical phenotypes are evasive and considered as knowledge gaps in food allergy diagnosis and risk management. Peanut allergy is a relevant disease model where pioneer discoveries were made in diagnosis, immunotherapy and prevention. This review provides an overview on the immune basis for phenotype variations in peanut-allergic individuals, in the light of future patient stratification along emerging omic-areas. Beyond specific IgE-signatures and basophil reactivity profiles with established correlation to clinical outcome, allergenomics, mass spectrometric resolution of peripheral allergen tracing, might be a fundamental approach to understand disease pathophysiology underlying biomarker discovery. Deep immune phenotyping is thought to reveal differential cell responses but also, gene expression and gene methylation profiles (eg, peanut severity genes) are promising areas for biomarker research. Finally, the study of microbiome-host interactions with a focus on the immune system modulation might hold the key to understand tissue-specific responses and symptoms. The immune mechanism underlying acute food-allergic events remains elusive until today. Deciphering this immunological response shall enable to identify novel biomarker for stratification of patients into reaction endotypes. The availability of powerful multi-omics technologies, together with integrated data analysis, network-based approaches and unbiased machine learning holds out the prospect of providing clinically useful biomarkers or biomarker signatures being predictive for reaction phenotypes.

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Increased diversity of gut microbiota during active oral immunotherapy in peanut‐allergic adults

Cited by 18 publications

References 10 publications

Mechanisms of oral immunotherapy

Mechanisms of oral immunotherapy

Insights into Microbiome and Metabolic Signatures of Children Undergoing Peanut Oral Immunotherapy

IgE-Mediated Peanut Allergy: Current and Novel Predictive Biomarkers for Clinical Phenotypes Using Multi-Omics Approaches

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