Abstract
Metabolite abnormalities are potentially implicated in pathogenesis of Hashimoto’s thyroiditis (HT). An in-depth study of the relationship between HT and small molecule metabolites, as well as its pathogenesis, can help enhance the diagnosis, prognosis, and treatment of HT patients. We used metabolomics to analyze changes in serum metabolite levels in 20 HT patients and 20 healthy controls (HC) and the most significant differentially expressed metabolite was analyzed. Western blot and qPCR were used to measure the expression of histidine decarboxylase (HDC) and histamine receptor 1 (H1R). Increasing concentrations of histidine were used to treat neutrophils and observe the effect on neutrophil extracellular traps (NETs) synthesis. Histidine treated neutrophils were co-culture with thyroid follicular cells to study the protective effects of histidine on HT thyroid follicular cells and related mechanisms. A total of 48 differentially expressed metabolites were found. Histidine exhibited reduced expression levels in HT patients, displaying the most significant discrepancy (p < 0.001). ROS and NETs were increased and HDC, H1R, and histamine were upregulated in neutrophils upon stimulated. These effects were corrected by addition of histidine, in a dose dependent manner. In addition, in co-culture experiments, histidine enhanced expression of SOD and suppressed production of inflammatory cytokines IL-6 and TNF-α and NF-κB pathway in thyroid follicular cells, thereby inhibiting inflammation and oxidative stress. Histidine inhibits NETs synthesis and NF-κB signaling. Thus, histidine play an anti-inflammatory and antioxidant role by decreasing thyroid follicular cell inflammation in HT.
Data availability
The datasets used and/or analyzed in the current study are available from the corresponding authors upon reasonable request. The raw sequencing data has been uploaded to the MetaboLights database. The original database link is: https://www.ebi.ac.uk/metabolights/editor/MTBLS12333/descriptors.
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We would like to thank all participants involved in this study.
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Bengbu Medical College Clinical Study Project (2022byflc007),First Affiliated Hospital of Bengbu Medical College High-Quality Technology Innovation Team (BYYFY2022TD001).
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TD and GJ conceived and designed the study, YW and LZ and XZ collected date and performed the statistical analysis. TD wrote the first draft which was revised by GJ and QW. The study was supervised by LZ and LY and CT. All the authors contributed to the study and approved the submitted version.
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The studies involving human participants were reviewed and approved by EC of the First Affiliated Hospital of Bengbu Medical University; The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, P.R. China. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Project batch number 2023YJS108.
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Ding, T., Wang, Y., Zhang, L. et al. Histidine alleviates Hashimoto’s thyroiditis via the neutrophil extracellular traps-NF-κB signaling pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45671-2
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DOI: https://doi.org/10.1038/s41598-026-45671-2