Imbalances in numerous circulating and urinary metabolites linked to development and progression of allergic diseases: Study

Researchers have found that imbalances in both circulating and urinary metabolites may play a crucial role in the pathogenesis and progression of allergic diseases including asthma, atopic dermatitis, and allergic rhinitis. A new study was recently published in the journal Respiratory Research. This study was conducted by Junhao and colleagues in China.

Allergic diseases significantly impact global health, necessitating deeper exploration into their underlying causes. Current treatments focus on symptom management, but there is a growing interest in addressing the root causes. Metabolites (small molecules involved in various physiological processes) have been implicated in immune and inflammatory responses. This study aimed to identify causal links between metabolites and allergic diseases to advance therapeutic approaches.

The researchers performed a two-sample MR analysis to assess causal interactions between 486 circulating metabolites and 55 urinary metabolites with allergic diseases. Data for allergic conditions, including asthma, AD, and AR, were drawn from two major biobanks: FinnGen (Europe, cohort 1) and Biobank Japan (Asia, cohort 2). It combined the findings of both the cohorts into a meta-analysis to improve the robustness of the results.

The main findings were:

Metabolites in Circulation:

  • Cohort 1 identified 50 circulating metabolites associated with allergic diseases, while cohort 2 identified 54.

  • Stearoylcarnitine emerged as the most reliable causal metabolite for asthma (OR 8.654; 95% CI: 4.399−17.025; P = 4.06E-10).

  • 1-arachidonoylglycerophosphoinositol was identified as a significant causal factor for AR (OR 2.178; 95% CI: 1.388−3.419; P = 7.15E-04).

Urinary Metabolites:

  • Six urinary metabolites were linked to allergic diseases in cohort 1, and two in cohort 2.

  • Histidine showed a protective effect against asthma (OR 0.734; 95% CI: 0.594−0.907; P = 0.004).

  • Tyrosine was protective against AD (OR 0.601; 95% CI: 0.380−0.952; P = 0.030).

  • Alanine reduced the risk of AR (OR 0.280; 95% CI: 0.125−0.628; P = 0.002).

The metabolite imbalances in circulation and urine are observed to be key issues in the manifestation of allergic diseases. Identification of stearoylcarnitine, 1-arachidonoylglycerophosphoinositol, histidine, tyrosine, and alanine as significant contributors provided insights into possible targets for innovative treatment strategies.

Reference:

Tu, J., Wen, J., Luo, Q., Li, X., Wang, D., & Ye, J. (2024). Causal relationships of metabolites with allergic diseases: a trans-ethnic Mendelian randomization study. Respiratory Research, 25(1). https://doi.org/10.1186/s12931-024-02720-6

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