A multi-omics analysis reveals that individuals with allergic rhinitis harbor a distinct microbial and metabolic fingerprint in their gut, which may contribute to amplifying nasal inflammation, highlighting new possibilities for microbiome-based treatments.
Study: Integrated gut microbiome and metabolomics analysis reveals microbial-metabolic cross-talk in allergic rhinitis. Image credit: Laia Balart/Shutterstock.com
New evidence suggests that gut dysbiosis may contribute to the development of allergic rhinitis; however, the specific role of gut microbes in this process remains unclear. A recent study published in the journal Frontiers in Microbiology aimed to investigate gut microbial profiles in individuals with allergic rhinitis.
Understanding allergic rhinitis
Allergic rhinitis is the most common allergic condition worldwide, carrying significant personal and societal costs and occurring alongside sinusitis or asthma in nearly half of all cases. Patients with allergic rhinitis have chronic inflammation of the mucosal lining of the nose and paranasal sinuses. This produces symptoms such as bouts of sneezing, a watery nasal discharge, nasal itching and congestion, often accompanied by eye itching.
Allergic rhinitis is driven by an imbalanced immune response, resulting in the release of immunoglobulin E (IgE) by sensitized lymphocytes, mast cell degranulation with the release of powerful inflammatory chemicals, and inflammation characterized by the presence of eosinophils.
However, emerging evidence suggests that the actual activation of type 2 innate lymphoid cells in allergic rhinitis occurs via the damage-associated molecular patterns (DAMPs) of the respiratory epithelium, such as interleukin (IL)-25. Additionally, dysbiosis, the interactions of neural and immune pathways, and the clinical features of the disease are equally important in understanding and classifying this disease for more effective management.
The correlations between gut dysbiosis and allergic rhinitis run throughout the pathway of allergic rhinitis, from its origin, pathogenesis, and progression. The underlying mechanisms relate to the immunological cascade, beginning at the gut mucosa, which serves as the contact point for gut microbes, and progressing through changes in the intestinal epithelial barrier to immunoregulatory processes at the gut level.
Dysbiosis at one site can affect allergic inflammation at distant sites in the same individual, due to the systemic nature of immune crosstalk. These pathways involve, for instance, the skin, gut, and lung in a single axis.
Microbes have multiple direct and indirect effects on host metabolism, immunity, and energy balance. For instance, some microbes produce short-chain fatty acids (SCFAs) and other immunomodulators that drive the differentiation of regulatory T cells (Tregs); indole derivatives that activate certain transcription regulators, such as the aryl hydrocarbon receptor pathway; and anti-inflammatory bile acids.
The distinctive alterations in gut microbiota observed in chronic rhinosinusitis are further evidence supporting the existence of the gut-nose axis. It suggests that inflammation of the sinuses and nasal mucosa has a common relationship with the gut. This could involve gut microbe translocation and immune conversations between different parts of the body, as well as between the immune system and other organs and tissues, influencing the response to infection, trauma, or disease.
The current study aimed to investigate the role of dysbiosis in causing allergic rhinitis, particularly through microbial metabolites that lead to dysregulated immunity via the gut-nose axis.
A multi-omics approach
The study included 23 patients with allergic rhinitis and 15 healthy control individuals. The scientists performed 16S rRNA gene sequencing to lay out the community structure of the gut microbiome. They also performed untargeted metabolomics to provide a comprehensive picture of microbial-origin metabolites.
They then assessed interactions between the gut microbiota and metabolites using Spearman’s rank correlation analysis.
Microbe-metabolite links identified
The scientists found that, despite unchanged overall diversity, patients with allergic rhinitis showed a different community structure compared to controls. For instance, taxa like Faecalibacterium, which produce SCFAs, were reduced, suggesting a decrease in immunoregulatory capacity. Conversely, potentially pathogenic inflammation-associated taxa, such as Fusobacterium, increased in abundance.
These microbial shifts could contribute to the systemic immune dysregulation seen in this condition. Importantly, the differences are primarily due to changes in low-abundance taxa, while the most common species remain largely intact. Such variations might escape analyses that focus only on the overall richness and evenness of the gut microbiota.
Metabolomics analysis revealed that vitamin synthetic pathways involving pantothenate and Coenzyme A (CoA) biosynthesis were disrupted in these patients. Energy-harvesting pathways were also affected. These suggest a role in altered immune and inflammatory responses.
The most notable metabolite shifts involved maltol and 4-coumaric acid. Maltol showed strong diagnostic performance, with an 84 % discriminative capacity and 74 % specificity for allergic rhinitis, and 4-coumaric acid displayed a similar pattern. The analysis identified specific key correlations between bacteria and metabolites, such as Faecalibacterium and D-phenyl lactic acid.
Overall, the host’s state of health and nutrition are likely to influence the protection or promotion of disease in association with these microbial changes. For instance, routinely eating too little fiber could be a risk factor for allergic rhinitis if SCFA-producing taxa (that feed on fermentable fiber in the gut) were reduced, since this would minimize resilience against such a change.
It is also possible that gut microbial metabolites do not cause, but rather exacerbate, inflammation arising in the nasopharyngeal microbiome, via the loss of gut-derived immunoregulatory factors.
Support for the gut-nose axis
The study suggests that allergic rhinitis is correlated with a characteristic gut dysbiosis and microbial metabolite profile, indicating a unique gut-nose axis picture compared to that occurring, for instance, in asthma. The findings emphasize the role played by gut dysbiosis and the resulting alterations in microbial metabolites, while reinforcing that these observations are associative rather than demonstrably causal in disrupting the immune tolerance typically achieved by the gut-nose axis.
These insights support the potential for microbiota-targeted therapeutic strategies in AR management.
However, further research is necessary to confirm the causal nature of these associations and translate them into a clinically relevant context.
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