Fecal and serum metabolomic signatures and gut microbiota characteristics of allergic rhinitis mice model.

Background: The etiology of allergic rhinitis (AR) is complicated. Traditional therapy of AR still has challenges, such as low long-term treatment compliance, unsatisfactory therapeutic outcomes, and a high financial burden. It is urgent to investigate the pathophysiology of allergic rhinitis from different perspectives and explore brand-new possible preventative or treatment initiatives. Objective: The aim is to apply a multi-group technique and correlation analysis to explore more about the pathogenesis of AR from the perspectives of gut microbiota, fecal metabolites, and serum metabolism. Methods: Thirty BALB/c mice were randomly divided into the AR and Con(control) groups. A standardized Ovalbumin (OVA)-induced AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. We detected the serum IL-4, IL-5, and IgE by enzyme-linked immunosorbent assay (ELISA), evaluated the histological characteristics of the nasal tissues by the hematoxylin and eosin (H&E) staining, and observed the nasal symptoms (rubs and sneezes) to evaluate the reliability of the AR mouse model. The colonic NF-κB protein was detected by Western Blot, and the colonic histological characteristics were observed by the H&E staining to evaluate inflammation of colon tissue. We analyzed the V3 and V4 regions of the 16S ribosomal DNA (rDNA) gene from the feces (colon contents) through 16S rDNA sequencing technology. Untargeted metabolomics was used to examine fecal and serum samples to find differential metabolites. Finally, through comparison and correlation analysis of differential gut microbiota, fecal metabolites, and serum metabolites, we further explore the overall impact of AR on gut microbiota, fecal metabolites, and host serum metabolism and its correlation. Results: In the AR group, the IL-4, IL-5, IgE, eosinophil infiltration, and the times of rubs and sneezes were significantly higher than those in the Con group, indicating the successful establishment of the AR model. No differences in diversity were detected between the AR and Con groups. However, there were modifications in the microbiota's structure. At the phylum level, the proportion of Firmicutes and Proteobacteria in the AR group increased significantly, while the proportion of Bacteroides decreased significantly, and the ratio of Firmicutes/Bacteroides was higher. The key differential genera, such as Ruminococcus, were increased significantly in the AR group, while the other key differential genera, such as Lactobacillus, Bacteroides, and Prevotella, were significantly decreased in the Con group. Untargeted metabolomics analysis identified 28 upregulated and 4 downregulated differential metabolites in feces and 11 upregulated and 16 downregulated differential metabolites in serum under AR conditions. Interestingly, one of the significant difference metabolites, α-Linoleic acid (ALA), decreased consistently in feces and serum of AR. KEGG functional enrichment analysis and correlation analysis showed a close relationship between differential serum metabolites and fecal metabolites, and changes in fecal and serum metabolic patterns are associated with altered gut microbiota in AR. The NF-κB protein and inflammatory infiltration of the colon increased considerably in the AR group. Conclusion: Our study reveals that AR alters fecal and serum metabolomic signatures and gut microbiota characteristics, and there is a striking correlation between the three. The correlation analysis of the microbiome and metabolome provides a deeper understanding of AR's pathogenesis, which may provide a theoretical basis for AR's potential prevention and treatment strategies.

Vancomycin-induced gut microbiota dysbiosis aggravates allergic rhinitis in mice by altered short-chain fatty acids.

Objective: This study aims to explore how gut microbiota dysbiosis affects allergic rhinitis (AR) and whether short-chain fatty acids (SCFAs) play a role in this process. Methods: A mouse gut microbiota dysbiosis model was established by adding vancomycin to drinking water for 2 weeks before ovalbumin (OVA) sensitization. Then an OVA-alum AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes in nasal and colon tissues of AR mice. Serum levels of total-IgE, OVA-sIgE, IL-4, IL-5, IL-10, and TGF-ß1 were measured. The composition and diversity of the mouse gut microbiota were observed by 16S rDNA sequencing. Levels of SCFAs in feces were determined using SCFA-targeted metabolomics. Sodium butyrate (NaB) was added daily to mice on a low-fiber basal diet 2 weeks before the first sensitization, until the end of the study. Results: After gut microbiota dysbiosis, serum levels of the total IgE, OVA-sIgE, IL-4, and IL-5 in AR mice were significantly increased, compared with the control group. The composition and diversity of gut microbiota were significantly altered after gut microbiota dysbiosis, with the fecal SCFAs significantly reduced as well. The reduced bacterial genera after gut microbiota dysbiosis, such as Ruminococcus and Lactobacillus, were significantly and positively correlated with SCFAs. In contrast, the increased genera in the Van group, such as Escherichia-Shigella and Klebsiella, were significantly negatively correlated with SCFAs in feces. NaB treatment significantly reduced total-IgE, OVA-sIgE, IL-4, and IL-5 levels in serum, and inflammatory infiltration of the nasal and colon mucosa. In addition, serum levels of IL-10 and TGF-ß1 increased significantly after NaB treatment. Foxp3 protein in the colon was upregulated considerably after NaB intervention. Conclusion: Vancomycin-induced gut microbiota dysbiosis increased susceptibility and severity of AR, which is significantly related to reduced SCFA-producing bacteria, fecal SCFAs, and specific bacterial taxa. In addition, it was found that NaB alleviated low dietary fiber base-fed symptoms and immune status in AR mice.