The common causal relationship between gut microbiota and respiratory diseases based on the theory of "lung and large intestine being interior-exterior related"_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CAO Zhenghua ¹ , HU Shaodan ² , SUN Feng ² , JIANG Guolu ¹ ,  SHI Li ²

1. School of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, 130117, P. R. China;
2. Department of Respiratory Medicine, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, P. R. China;

Corresponding?author：

SHI Li, Email: shili0648@163.com

Keywords：

Mendelian randomization; gut microbiota; respiratory system diseases; causal relationship; chronic obstructive pulmonary disease

DOI：

10.7507/1007-4848.202408017

Video：

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Objective To comprehensively evaluate the causal relationship between gut microbiota and 9 respiratory diseases, explore whether there are common mechanisms among these 9 respiratory diseases, and delves into the potential commonalities of pre-chronic obstructive pulmonary disease (pre-COPD) by focusing on COPD, emphysema, and chronic bronchitis. Methods Mendelian randomization was used to explore the causal relationship between gut microbiota and 9 respiratory diseases, sensitivity analysis was conducted, and robustness was verified. Single nucleotide polymorphisms of common gut microbiota were mapped to genes to explore their common mechanisms. Results Mendelian randomization studies found that 66 gut microbiota had a causal relationship with 9 respiratory diseases, and 15 gut microbiota might be potential common mechanisms for these 9 respiratory diseases, with a total of 85 potential genes. GO functional enrichment analysis found that these genes were mainly enriched in biological functions such as synaptic transmission, synaptic membrane, cytokine activity, and growth factor binding. KEGG enrichment analysis showed that these genes were mainly enriched in glutamatergic synapses, relaxin signaling pathway, calcium signaling pathway, Rap1 signaling pathway, and PI3K-Akt signaling pathway. Allisonella and Prevotellaceae might be protective factors for pre-COPD, while Howardella might be a risk factor. Ten protective genes and six risk genes for the pre-COPD were identified. Conclusion This study further confirms the correlation between the lung-gut axis and the lung-colon connection, explores the potential common mechanisms of 9 respiratory diseases, investigates the potential mechanisms of pre-COPD based on the common gut microbiota of COPD, chronic bronchitis, and emphysema, and provides some ideas for the early prevention and treatment of COPD, and diagnosis of pre-COPD from the perspective of gut microbiota.

Citation： CAO Zhenghua, HU Shaodan, SUN Feng, JIANG Guolu, SHI Li. The common causal relationship between gut microbiota and respiratory diseases based on the theory of "lung and large intestine being interior-exterior related". Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2026, 33(8): 1282-1289. doi: 10.7507/1007-4848.202408017 Copy

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1. 莫芳芳, 馬師雷, 李鴻濤, 等. 基于中醫古籍研究的 "肺與大腸相表里" 理論源流及其內涵探討[J]. 環球中醫藥, 2015, 8(2): 165-168.Mo FF, Ma SL, Li HT, et al. Discussion on the origin and connotation of the "lung and large intestine being interior exteriorly related" based on TCM classics[J]. Glob Tradit Chin Med, 2015, 8(2): 165-168.
2. 張蕓, 史鎖芳. "肺與大腸相表里" 學說的現代研究進展[J]. 中醫研究, 2015, 28(5): 73-75.Zhang Y, Shi SF. Modern research progress of the theory of "lung and large intestine are external and internal"[J]. Tradit Chin Med Res, 2015, 28(5): 73-75.
3. 李玉平, 翟海英, 楊長福. "肺與大腸相表里" 理論的研究[J]. 中國中醫基礎醫學雜志, 2024, 30(2): 336-341.Li YP, Zhai HY, Yang CF. Research on the theory of "lung and large intestine connecting externally and internally"[J]. J Basic Chin Med, 2024, 30(2): 336-341.
4. 劉聲, 楊國旺, 王笑民. 從胚胎上皮細胞基因表達譜變化分析肺與大腸相表里內涵[J]. 中醫學報, 2016, 31(3): 390-393.Liu S, Yang GW, Wang XM. The connotation of lung and large intestine being interior-exteriorly related based on the gene expression of embryo epithelial cells[J]. Acta Chin Med, 2016, 31(3): 390-393.
5. Wang X, Hou L, Cui M, et al. The traditional Chinese medicine and non-small cell lung cancer: from a gut microbiome perspective[J]. Front Cell Infect Microbiol, 2023, 13: 1151557.
6. 彭楊月, 常滿, 牛盼迪, 等. 發酵中藥改善腸道屏障和腸道菌群的研究進展[J]. 中國現代應用藥學, 2023, 40(11): 1563-1570.Peng YY, Chang M, Niu PD, et al. Research progress of fermented traditional chinese medicine in improving intestinal barrier and intestinal flora[J]. Chin J Mod Appl Pharm, 2023, 40(11): 1563-1570.
7. 段曉穎, 邢慧資, 桑鋒, 等. 中藥對腸黏膜屏障的作用機制研究進展[J]. 中國現代應用藥學, 2019, 36(16): 2106-2111.Duan XY, Xing HZ, Sang F, et al. Research progress on mechanism of traditional Chinese medicine on intestinal mucosal barrier[J]. Chin J Mod Appl Pharm, 2019, 36(16): 2106-2111.
8. 王晗笑, 欒哲宇, 封繼宏. 基于 "肺與大腸相表里" 探討中醫藥調控腸道菌群治療慢性阻塞性肺疾病的內涵[J]. 中國實驗方劑學雜志, 2024, 30(3): 169-177.Wang HX, Luan ZY, Feng JH. Connotation of traditional Chinese medicine in treatment of chronic obstructive pulmonary disease by regulating gut microbiota based on "lung and large intestine being interior-exterior related"[J]. Chin J Exp Tradit Med Form, 2024, 30(3): 169-177.
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Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

The common causal relationship between gut microbiota and respiratory diseases based on the theory of "lung and large intestine being interior-exterior related"

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