Abstract
Allergic rhinitis (AR) is an allergic condition of the upper respiratory tract with a complex pathogenesis, including epithelial barrier disruption, immune regulation, and gut microbiota, which is not yet fully understood. Gut microbiota is closely linked to allergic diseases, including AR. Fecal microbiota transplantation (FMT) has recently been recognized as a potentially effective therapy for allergic diseases. However, the efficacy and mechanism of action of FMT in AR remain unknown. Herein, we aimed to observe the implications of gut microbiota on epithelial barrier function and T cell homeostasis, as well as the effect of FMT in AR, using the ovalbumin (OVA)-induced AR mice. The intestinal microbiota of recipient mice was cleared using an antibiotic cocktail; thereafter, FMT was performed. Subsequently, the nasal symptom scores and histopathological features of colon and nasal mucosa tissues of mice were monitored, and serum OVA-sIgE and cytokines of IL-4, IFNγ, IL-17A, and IL-10 cytokine concentrations were examined. Thereafter, tight junction protein and CD4+ T cell-related transcription factor and cytokine expressions were observed in the colon and nasal mucosa, and changes in the expression of PI3K/AKT/mTOR and NFκB signaling pathway were detected by WB assay in each group. Fecal DNA was extracted from the four mice groups for high-throughput 16S rRNA sequencing. FMT ameliorated nasal symptoms and reduced nasal mucosal inflammation in AR mice. Moreover, according to 16S rRNA sequencing, FMT restored the disordered gut microbiota in AR mice. Following FMT, ZO-1 and claudin-1 and Th1/Th2/Th17-related transcription factor and cytokine expressions were upregulated, whereas Treg cell-related Foxp3 and IL-10 expressions were downregulated. Mechanistic studies have revealed that FMT also inhibited PI3K/AKT/mTOR and NF-κB pathway protein phosphorylation in AR mouse tissues. FMT alleviates allergic inflammation in AR by repairing the epithelial barrier and modulating CD4+ T cell balance and exerts anti-inflammatory effects through the PI3K/AKT/mTOR and NF-κB signaling pathways. Moreover, gut microbiota disorders are involved in AR pathogenesis. Disturbed gut microbiota causes an altered immune-inflammatory state in mice and increases susceptibility to AR. This study suggested the regulatory role of the gut-nose axis in the pathogenesis of AR is an emerging field, which provides novel directions and ideas for the treatment of AR.
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Data available on request from the authors.
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The National Natural Science Foundation of China (No. 81970860) provided funding for this study.
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LD conducted experiments and drafted the manuscript. YT and SW helped in conducting the animal experiments. YH and FL helped in collecting the data. YD and ZT conceived the original idea and revised the manuscript. All authors reviewed the manuscript.
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Dong, L., Tang, Y., Wen, S. et al. Fecal Microbiota Transplantation Alleviates Allergic Rhinitis via CD4+ T Cell Modulation Through Gut Microbiota Restoration. Inflammation (2024). https://doi.org/10.1007/s10753-024-01975-x
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DOI: https://doi.org/10.1007/s10753-024-01975-x