Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (3): 571-583.DOI: 10.19852/j.cnki.jtcm.2026.03.005
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Mechanism of Buzhong Yiqi decoction (补中益气汤) for Hashimoto's thyroiditis: insights from gut microbiota and metabolomics
CHEN Ying1, QIAO Jiajun2, LU Yuyuan1, XUE Chongxiang3, XIA Zhongyuan2(
)
- 1
Graduate School ,Beijing University of Chinese Medicine, Beijing 100029, China; Surgery of Traditional Chinese Medicine, China-Japan Friendship Hospital Beijing 100029, China
2Surgery of Traditional Chinese Medicine ,China-Japan Friendship Hospital Beijing 100029, China
3Department of Endocrinology ,the Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310009, China
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Received:2024-12-19Accepted:2025-09-12Online:2026-06-15Published:2026-06-08 -
Contact:Prof. XIA Zhongyuan, Department of Surgery of Traditional Chinese Medicine, China-Japan Friendship Hospital, Beijing 100029, China. zryhyy1961@163.com, Telephone: +86-10-84205309 -
About author:First author contact:CHEN Ying and QIAO Jiajun are co-first authors and contributed equally to this work
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Supported by:National High Level Hospital Clinical Research Funding: Study on the Mechanism of the Gut Microbiota Participating in the Metabolic Regulation Therapy of Hashimoto's Thyroiditis by Buzhong Yiqi decoction(2023-NHLHCRF-BQ-28);Tongchuan Thyroid Disease Prevention Center 2023 Research Special Youth Project: Study on the Mechanism of Buzhong Yiqi decoction in Treating Hashimoto's Thyroiditis by Improving Gut Mucosal Barrier(TJF-QN-2023-06);National Natural Science Foundation of China: Action Mechanism of Buzhong Yiqi decoction in Treating Hashimoto's Thyroiditis Based on Transforming Growth Factor β/Smad Signaling Pathway and the Balance between Treg and Th17 Cells(81973855)
Cite this article
CHEN Ying, QIAO Jiajun, LU Yuyuan, XUE Chongxiang, XIA Zhongyuan. Mechanism of Buzhong Yiqi decoction (补中益气汤) for Hashimoto's thyroiditis: insights from gut microbiota and metabolomics[J]. Journal of Traditional Chinese Medicine, 2026, 46(3): 571-583.
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Figure 1 Therapeutic effects of BZYQ on AIT rats A: thyroid tissue HE staining sections (× 20); B: serum TPOAb by ELISA detection; C: serum TGAb by ELISA detection; D: colon tissue HE staining sections (× 20); A1, D1: control group; A2, D2: model group; A3, D3: BZYQ group; A4, D4: ABX group; A5, D5: ABX_BZYQ group. BZYQ group: the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks; ABX group: the AIT received ceftriaxone sodium (350 mg/kg) and gentamicin sulfate (126mg/kg) at a rate of 1 mL·g-1;·d-1;, administered twice daily for 6 consecutive days, to deplete the gut microbiota; ABX_BZYQ group: After deplete the gut microbiota, the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks. BZYQ: Buzhong Yiqi decoction; ABX: antibiotics; AIT: autoimmune thyroiditis; TPOAb: thyroid peroxidase antibody; TGAb: thyroglobulin antibody; HE: hematoxylin and eosin; ELISA: enzyme linked immunosorbent assay; The data were expressed as mean ± standard deviation (n = 6) and analyzed using one-way analysis of variance with Dunnett's post hoc test. aP < 0.05 vs control group; bP < 0.05 vs model group; cP < 0.05 vs BZYQ group.
Figure 1 Therapeutic effects of BZYQ on AIT rats A: thyroid tissue HE staining sections (× 20); B: serum TPOAb by ELISA detection; C: serum TGAb by ELISA detection; D: colon tissue HE staining sections (× 20); A1, D1: control group; A2, D2: model group; A3, D3: BZYQ group; A4, D4: ABX group; A5, D5: ABX_BZYQ group. BZYQ group: the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks; ABX group: the AIT received ceftriaxone sodium (350 mg/kg) and gentamicin sulfate (126mg/kg) at a rate of 1 mL·g-1;·d-1;, administered twice daily for 6 consecutive days, to deplete the gut microbiota; ABX_BZYQ group: After deplete the gut microbiota, the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks. BZYQ: Buzhong Yiqi decoction; ABX: antibiotics; AIT: autoimmune thyroiditis; TPOAb: thyroid peroxidase antibody; TGAb: thyroglobulin antibody; HE: hematoxylin and eosin; ELISA: enzyme linked immunosorbent assay; The data were expressed as mean ± standard deviation (n = 6) and analyzed using one-way analysis of variance with Dunnett's post hoc test. aP < 0.05 vs control group; bP < 0.05 vs model group; cP < 0.05 vs BZYQ group.
Figure 2 Comparative analysis of inter-group differences. A: PCoA analysis based on Unweighted Unifrac distances of ASVs; B: PCA analysis based on ASVs; C: UPGMA dendrogram based on Weighted Unifrac distances of ASVs. BZYQ group: the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks; ABX group: the AIT received ceftriaxone sodium (350 mg/kg) and gentamicin sulfate (126 mg/kg) at a rate of 1 mL·g-1;·d-1;, administered twice daily for 6 consecutive days, to deplete the gut microbiota; ABX_BZYQ group: after deplete the gut microbiota, the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks; BZYQ: Buzhong Yiqi decoction; ABX: antibiotics; PCoA: principal coordinates analysis; ASVs: amplicon sequence variants; PCA: principal component analysis; UPGMA: unweighted pair-group method with arithmetic means; AIT: autoimmune thyroiditis.
Figure 2 Comparative analysis of inter-group differences. A: PCoA analysis based on Unweighted Unifrac distances of ASVs; B: PCA analysis based on ASVs; C: UPGMA dendrogram based on Weighted Unifrac distances of ASVs. BZYQ group: the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks; ABX group: the AIT received ceftriaxone sodium (350 mg/kg) and gentamicin sulfate (126 mg/kg) at a rate of 1 mL·g-1;·d-1;, administered twice daily for 6 consecutive days, to deplete the gut microbiota; ABX_BZYQ group: after deplete the gut microbiota, the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks; BZYQ: Buzhong Yiqi decoction; ABX: antibiotics; PCoA: principal coordinates analysis; ASVs: amplicon sequence variants; PCA: principal component analysis; UPGMA: unweighted pair-group method with arithmetic means; AIT: autoimmune thyroiditis.
Table 1 MRPP analysis of iInter-group differences based on ASVs
| Group | A | Observed_delta | Expected_delta | Significance |
|---|---|---|---|---|
| Model_vs_Control | 0.101532212 | 0.603127707 | 0.671284731 | 0.003329634 |
| Model_vs_ABX | 0.495838186 | 0.35331937 | 0.700805495 | 0.004439512 |
| Model_vs_BZYQ | 0.099030148 | 0.599985484 | 0.665932919 | 0.007769145 |
| ABX_vs_ABX_BZYQ | 0.469687222 | 0.37734158 | 0.711545329 | 0.00554939 |
Table 1 MRPP analysis of iInter-group differences based on ASVs
| Group | A | Observed_delta | Expected_delta | Significance |
|---|---|---|---|---|
| Model_vs_Control | 0.101532212 | 0.603127707 | 0.671284731 | 0.003329634 |
| Model_vs_ABX | 0.495838186 | 0.35331937 | 0.700805495 | 0.004439512 |
| Model_vs_BZYQ | 0.099030148 | 0.599985484 | 0.665932919 | 0.007769145 |
| ABX_vs_ABX_BZYQ | 0.469687222 | 0.37734158 | 0.711545329 | 0.00554939 |
Figure 3 LEfSe analysis A: phylogenetic tree based on ASVs (In the phylogenetic tree, the radiating circles from the center represent the taxonomic levels from phylum to genus (or species). Each small circle at different taxonomic levels represents a classification at that level, and the diameter of the small circle is proportional to the relative abundance. Coloring principle: Species with no significant difference are uniformly colored yellow, and differential species Biomarkers are colored according to the group. Red nodes indicate microbial groups that play an important role in the red group, and green nodes indicate microbial groups that play an important role in the green group. If a group is missing in the Figure, it means there are no significantly different species in this group, hence the group is missing. The species names represented by English letters in the Figure are displayed in the legend on the right); B: bar chart of LDA values based on ASVs. The bar chart of LDA values shows species with LDA Scores greater than the set value (default is 4), i.e., Biomarkers with statistical differences between groups. It displays the species with significant abundance differences in different groups, and the length of the bar chart represents the impact size of the differential species (i.e., LDA Score); BZYQ group: the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks. BZYQ: Buzhong Yiqi decoction; LEfSe: linear discriminant analysis effect size; ASVs: amplicon sequence variants; LDA: linear discriminant analysis.
Figure 3 LEfSe analysis A: phylogenetic tree based on ASVs (In the phylogenetic tree, the radiating circles from the center represent the taxonomic levels from phylum to genus (or species). Each small circle at different taxonomic levels represents a classification at that level, and the diameter of the small circle is proportional to the relative abundance. Coloring principle: Species with no significant difference are uniformly colored yellow, and differential species Biomarkers are colored according to the group. Red nodes indicate microbial groups that play an important role in the red group, and green nodes indicate microbial groups that play an important role in the green group. If a group is missing in the Figure, it means there are no significantly different species in this group, hence the group is missing. The species names represented by English letters in the Figure are displayed in the legend on the right); B: bar chart of LDA values based on ASVs. The bar chart of LDA values shows species with LDA Scores greater than the set value (default is 4), i.e., Biomarkers with statistical differences between groups. It displays the species with significant abundance differences in different groups, and the length of the bar chart represents the impact size of the differential species (i.e., LDA Score); BZYQ group: the AIT received BZYQ at a rate of 1 mL·g-1;·d-1;, once daily for 8 consecutive weeks. BZYQ: Buzhong Yiqi decoction; LEfSe: linear discriminant analysis effect size; ASVs: amplicon sequence variants; LDA: linear discriminant analysis.
Figure 4 Hierarchical clustering heatmap of spearman correlations between differential microbiota and metabolites in model and BZYQ groups A: phylum level; B: genus level; C: species level. Rows represent microbes, and columns represent metabolites. The dendrogram on the left indicates the hierarchical clustering results of the microbes, and the dendrogram at the top indicates the hierarchical clustering results of the metabolites. Red indicates positive correlation, and green indicates negative correlation. The data analyzed using Spearman correlation analysis. *P < 0.05, **P < 0.01. BZYQ: Buzhong Yiqi decoction.
Figure 4 Hierarchical clustering heatmap of spearman correlations between differential microbiota and metabolites in model and BZYQ groups A: phylum level; B: genus level; C: species level. Rows represent microbes, and columns represent metabolites. The dendrogram on the left indicates the hierarchical clustering results of the microbes, and the dendrogram at the top indicates the hierarchical clustering results of the metabolites. Red indicates positive correlation, and green indicates negative correlation. The data analyzed using Spearman correlation analysis. *P < 0.05, **P < 0.01. BZYQ: Buzhong Yiqi decoction.
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