微生物群和色氨酸参与支气管肺发育不良发病的研究进展
Research Progress on the Involvement of Microbiota and Tryptophan in the Pathogenesis of Bronchopulmonary Dysplasia
DOI: 10.12677/acm.2026.163911, PDF,   
作者: 邓荷钰, 包 蕾*：重庆医科大学附属儿童医院新生儿科，儿童少年健康与疾病国家临床医学研究中心，儿童发育疾病研究教育部重点实验室，儿童神经发育与认知障碍重庆市重点实验室，重庆
关键词: 色氨酸；支气管肺发育不良；肠–肺轴；微生物群；Tryptophan； Bronchopulmonary Dysplasia； Gut-Lung Axis； Microbiota
摘要: 支气管肺发育不良(Bronchopulmonary Dysplasia, BPD)是一种见于早产儿的慢性肺部疾病，其发生发展与多因素相互作用相关，并常导致心血管、神经等多系统远期后遗症。近年来，随着“肠–肺轴”概念的提出及深入研究，肠道微生物群及其代谢产物在BPD发病中的作用日益受到关注。色氨酸作为必需氨基酸，其代谢产物在免疫调节、屏障保护等方面具有重要作用。本文综述了肠道微生物及色氨酸代谢在BPD中的作用，重点总结BPD中存在的肠道菌群失调与色氨酸代谢紊乱及其潜在意义，旨在为深入理解BPD的发病机制及相关防治策略提供新的视角。
Abstract: Bronchopulmonary Dysplasia (BPD) is a chronic lung disease observed in premature infants, whose development is associated with the interplay of multiple factors and often leads to long-term sequelae in multiple systems such as the cardiovascular and nervous systems. In recent years, with the proposal and in-depth research on the concept of the “gut-lung axis,” the role of gut microbiota and their metabolites in the pathogenesis of BPD has garnered increasing attention. Tryptophan, as an essential amino acid, plays a significant role in immune regulation and barrier protection through its metabolites. This article reviews the role of gut microbiota and tryptophan metabolism in BPD, focusing on summarizing the dysbiosis of gut microbiota and disturbances in tryptophan metabolism in BPD and their potential implications, aiming to provide new perspectives for a deeper understanding of the pathogenesis of BPD and related prevention and treatment strategies.
文章引用：邓荷钰, 包蕾. 微生物群和色氨酸参与支气管肺发育不良发病的研究进展[J]. 临床医学进展, 2026, 16(3): 1330-1338. https://doi.org/10.12677/acm.2026.163911

参考文献

[1] Zhu, Z., Yuan, L., Wang, J., Li, Q., Yang, C., Gao, X., et al. (2021) Mortality and Morbidity of Infants Born Extremely Preterm at Tertiary Medical Centers in China from 2010 to 2019. JAMA Network Open, 4, e219382. [Google Scholar] [CrossRef] [PubMed]
[2] Jeon, G.W., Oh, M. and Chang, Y.S. (2025) Increased Bronchopulmonary Dysplasia along with Decreased Mortality in Extremely Preterm Infants. Scientific Reports, 15, Article No. 8720. [Google Scholar] [CrossRef] [PubMed]
[3] Bell, E.F., Hintz, S.R., Hansen, N.I., Bann, C.M., Wyckoff, M.H., DeMauro, S.B., et al. (2022) Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA, 327, 248-263. [Google Scholar] [CrossRef] [PubMed]
[4] Hansmann, G., Sallmon, H., Roehr, C.C., Kourembanas, S., Austin, E.D. and Koestenberger, M. (2020) Pulmonary Hypertension in Bronchopulmonary Dysplasia. Pediatric Research, 89, 446-455. [Google Scholar] [CrossRef] [PubMed]
[5] Homan, T.D. and Nayak, R.P. (2021) Short-and Long-Term Complications of Bronchopulmonary Dysplasia. Respiratory Care, 66, 1618-1629. [Google Scholar] [CrossRef] [PubMed]
[6] Ambalavanan, N., Deutsch, G., Pryhuber, G., Travers, C.P. and Willis, K.A. (2026) The Evolving Pathophysiology of Bronchopulmonary Dysplasia. Physiological Reviews, 106, 197-237. [Google Scholar] [CrossRef] 
[7] van Horik, C., Meyboom, J., Boerema-de Munck, A., Buscop-van Kempen, M., Eenjes, E., Edel, G.G., et al. (2025) The Impact of Hyperoxia and Antibiotics on Lung Mesenchymal Cells in Experimental Bronchopulmonary Dysplasia. American Journal of Physiology-Lung Cellular and Molecular Physiology, 329, L440-L454. [Google Scholar] [CrossRef] [PubMed]
[8] Agus, A., Planchais, J. and Sokol, H. (2018) Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host & Microbe, 23, 716-724. [Google Scholar] [CrossRef] [PubMed]
[9] Zelante, T., Iannitti, R.G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., et al. (2013) Tryptophan Catabolites from Microbiota Engage Aryl Hydrocarbon Receptor and Balance Mucosal Reactivity via Interleukin-22. Immunity, 39, 372-385. [Google Scholar] [CrossRef] [PubMed]
[10] Deng, Y., Zhou, M., Wang, J., Yao, J., Yu, J., Liu, W., et al. (2021) Involvement of the Microbiota-Gut-Brain Axis in Chronic Restraint Stress: Disturbances of the Kynurenine Metabolic Pathway in Both the Gut and Brain. Gut Microbes, 13, 1-16. [Google Scholar] [CrossRef] [PubMed]
[11] Xue, C., Li, G., Zheng, Q., Gu, X., Shi, Q., Su, Y., et al. (2023) Tryptophan Metabolism in Health and Disease. Cell Metabolism, 35, 1304-1326. [Google Scholar] [CrossRef] [PubMed]
[12] Zhang, L.S. and Davies, S.S. (2016) Microbial Metabolism of Dietary Components to Bioactive Metabolites: Opportunities for New Therapeutic Interventions. Genome Medicine, 8, Article No. 46. [Google Scholar] [CrossRef] [PubMed]
[13] Özçam, M. and Lynch, S.V. (2024) The Gut-Airway Microbiome Axis in Health and Respiratory Diseases. Nature Reviews Microbiology, 22, 492-506. [Google Scholar] [CrossRef] [PubMed]
[14] Ni, S., Yuan, X., Cao, Q., Chen, Y., Peng, X., Lin, J., et al. (2023) Gut Microbiota Regulate Migration of Lymphocytes from Gut to Lung. Microbial Pathogenesis, 183, Article ID: 106311. [Google Scholar] [CrossRef] [PubMed]
[15] Marsland, B.J., Trompette, A. and Gollwitzer, E.S. (2015) The Gut-Lung Axis in Respiratory Disease. Annals of the American Thoracic Society, 12, S150-S156. [Google Scholar] [CrossRef] [PubMed]
[16] Tirone, C., Pezza, L., Paladini, A., Tana, M., Aurilia, C., Lio, A., et al. (2019) Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes. Frontiers in Immunology, 10, Article No. 2910. [Google Scholar] [CrossRef] [PubMed]
[17] Enaud, R., Prevel, R., Ciarlo, E., Beaufils, F., Wieërs, G., Guery, B., et al. (2020) The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks. Frontiers in Cellular and Infection Microbiology, 10, Article No. 9. [Google Scholar] [CrossRef] [PubMed]
[18] Lee, C., Feng, Y., Yeh, Y., Lien, R., Chen, C., Zhou, Y., et al. (2021) Gut Dysbiosis, Bacterial Colonization and Translocation, and Neonatal Sepsis in Very-Low-Birth-Weight Preterm Infants. Frontiers in Microbiology, 12, Article ID: 746111. [Google Scholar] [CrossRef] [PubMed]
[19] Xiang, Q., Yan, X., Shi, W., Li, H. and Zhou, K. (2023) Early Gut Microbiota Intervention in Premature Infants: Application Perspectives. Journal of Advanced Research, 51, 59-72. [Google Scholar] [CrossRef] [PubMed]
[20] Korpela, K., Blakstad, E.W., Moltu, S.J., Strømmen, K., Nakstad, B., Rønnestad, A.E., et al. (2018) Intestinal Microbiota Development and Gestational Age in Preterm Neonates. Scientific Reports, 8, Article No. 2453. [Google Scholar] [CrossRef] [PubMed]
[21] Tauchi, H., Yahagi, K., Yamauchi, T., Hara, T., Yamaoka, R., Tsukuda, N., et al. (2019) Gut Microbiota Development of Preterm Infants Hospitalised in Intensive Care Units. Beneficial Microbes, 10, 641-652. [Google Scholar] [CrossRef] [PubMed]
[22] Kennedy, P.J., Cryan, J.F., Dinan, T.G. and Clarke, G. (2017) Kynurenine Pathway Metabolism and the Microbiota-Gut-Brain Axis. Neuropharmacology, 112, 399-412. [Google Scholar] [CrossRef] [PubMed]
[23] Xiong, S., Sun, H., Lu, C., He, J., Wu, Z., Wang, Y., et al. (2023) Kuqin Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by Regulating Indoleamine 2,3-Dioxygenase 1 and Akkermansia muciniphila. Biomedicine & Pharmacotherapy, 158, Article ID: 114073. [Google Scholar] [CrossRef] [PubMed]
[24] Zhang, Y., Tu, S., Ji, X., Wu, J., Meng, J., Gao, J., et al. (2024) Dubosiella Newyorkensis Modulates Immune Tolerance in Colitis via the L-Lysine-Activated AhR-IDO1-kyn Pathway. Nature Communications, 15, Article No. 1333. [Google Scholar] [CrossRef] [PubMed]
[25] Tanaka, M. and Vécsei, L. (2025) From Microbial Switches to Metabolic Sensors: Rewiring the Gut-Brain Kynurenine Circuit. Biomedicines, 13, Article No. 2020. [Google Scholar] [CrossRef] 
[26] Martin-Gallausiaux, C., Larraufie, P., Jarry, A., Béguet-Crespel, F., Marinelli, L., Ledue, F., et al. (2018) Butyrate Produced by Commensal Bacteria Down-Regulates Indolamine 2,3-Dioxygenase 1 (IDO-1) Expression via a Dual Mechanism in Human Intestinal Epithelial Cells. Frontiers in Immunology, 9, Article No. 2838. [Google Scholar] [CrossRef] [PubMed]
[27] Liu, N., Sun, S., Wang, P., Sun, Y., Hu, Q. and Wang, X. (2021) The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine. International Journal of Molecular Sciences, 22, Article No. 7931. [Google Scholar] [CrossRef] [PubMed]
[28] Myung, W., Jang, S.J., Lee, G., Lee, C., Lee, K., Moon, S.H., et al. (2025) Oral Administration of Lactiplantibacillus plantarum KBL396 Regulates Serum 5-Hydroxytryptamine and Gut Microbiota: Evidence from a Preclinical Mouse Model and a Randomized Controlled Human Trial. Probiotics and Antimicrobial Proteins. [Google Scholar] [CrossRef] 
[29] Esmaili, A., Nazir, S.F., Borthakur, A., Yu, D., Turner, J.R., Saksena, S., et al. (2009) Enteropathogenic Escherichia coli Infection Inhibits Intestinal Serotonin Transporter Function and Expression. Gastroenterology, 137, 2074-2083. [Google Scholar] [CrossRef] [PubMed]
[30] Roager, H.M. and Licht, T.R. (2018) Microbial Tryptophan Catabolites in Health and Disease. Nature Communications, 9, Article No. 3294. [Google Scholar] [CrossRef] [PubMed]
[31] Jiang, L., Hao, Y., Han, D., Dong, W., Yang, A., Sun, Z., et al. (2024) Gut Microbiota Dysbiosis Deteriorates Immunoregulatory Effects of Tryptophan via Colonic Indole and LBP/HTR2B-Mediated Macrophage Function. The ISME Journal, 18, wrae166. [Google Scholar] [CrossRef] [PubMed]
[32] Pan, H., Yang, S., Kulyar, M.F., Ma, H., Li, K., Zhang, L., et al. (2025) Lactobacillus fermentum 016 Alleviates Mice Colitis by Modulating Oxidative Stress, Gut Microbiota, and Microbial Metabolism. Nutrients, 17, Article No. 452. [Google Scholar] [CrossRef] [PubMed]
[33] Savitz, J. (2019) The Kynurenine Pathway: A Finger in Every Pie. Molecular Psychiatry, 25, 131-147. [Google Scholar] [CrossRef] [PubMed]
[34] Stockinger, B., Shah, K. and Wincent, E. (2021) AHR in the Intestinal Microenvironment: Safeguarding Barrier Function. Nature Reviews Gastroenterology & Hepatology, 18, 559-570. [Google Scholar] [CrossRef] [PubMed]
[35] Li, M., Ding, Y., Wei, J., Dong, Y., Wang, J., Dai, X., et al. (2024) Gut Microbiota Metabolite Indole-3-Acetic Acid Maintains Intestinal Epithelial Homeostasis through Mucin Sulfation. Gut Microbes, 16, Article ID: 2377576. [Google Scholar] [CrossRef] [PubMed]
[36] Pamart, G., Gosset, P., Le Rouzic, O., Pichavant, M. and Poulain-Godefroy, O. (2024) Kynurenine Pathway in Respiratory Diseases. International Journal of Tryptophan Research, 17. [Google Scholar] [CrossRef] [PubMed]
[37] Renga, G., D’Onofrio, F., Pariano, M., Galarini, R., Barola, C., Stincardini, C., et al. (2023) Bridging of Host-Microbiota Tryptophan Partitioning by the Serotonin Pathway in Fungal Pneumonia. Nature Communications, 14, Article No. 5753. [Google Scholar] [CrossRef] [PubMed]
[38] Fan, T., Lu, L., Jin, R., Sui, A., Guan, R., Cui, F., et al. (2022) Change of Intestinal Microbiota in Mice Model of Bronchopulmonary Dysplasia. PeerJ, 10, e13295. [Google Scholar] [CrossRef] [PubMed]
[39] Ning, T., Shan, X., Zhuang, X., Li, B., Zhang, Y., Chen, T., et al. (2025) Intestinal Microbiota Changes in Early Life of Very Preterm Infants with Bronchopulmonary Dysplasia: A Nested Case-Control Study. Frontiers in Microbiology, 16, Article ID: 1632412. [Google Scholar] [CrossRef] [PubMed]
[40] Bao, Z., Niu, L., Ma, Y., Deng, X., Wang, L., Tao, M., et al. (2025) Characterization of the Airway Microbiome in Preterm Infants with Bronchopulmonary Dysplasia. Frontiers in Cellular and Infection Microbiology, 15, Article ID: 1654502. [Google Scholar] [CrossRef] 
[41] Gallacher, D., Mitchell, E., Alber, D., Wach, R., Klein, N., Marchesi, J.R., et al. (2020) Dissimilarity of the Gut-Lung Axis and Dysbiosis of the Lower Airways in Ventilated Preterm Infants. European Respiratory Journal, 55, Article ID: 1901909. [Google Scholar] [CrossRef] [PubMed]
[42] Zhang, M., Li, D., Sun, L., He, Y., Liu, Q., He, Y., et al. (2024) Lactobacillus reuteri Alleviates Hyperoxia‐Induced BPD by Activating IL‐22/STAT3 Signaling Pathway in Neonatal Mice. Mediators of Inflammation, 2024, Article ID: 4965271. [Google Scholar] [CrossRef] [PubMed]
[43] Delaney, C., Sherlock, L., Fisher, S., Maltzahn, J., Wright, C. and Nozik-Grayck, E. (2018) Serotonin 2A Receptor Inhibition Protects against the Development of Pulmonary Hypertension and Pulmonary Vascular Remodeling in Neonatal Mice. American Journal of Physiology-Lung Cellular and Molecular Physiology, 314, L871-L881. [Google Scholar] [CrossRef] [PubMed]
[44] Ruan, Q., Peng, Y., Yi, X., Yang, J., Ai, Q., Liu, X., et al. (2025) The Tryptophan Metabolite 3-Hydroxyanthranilic Acid Alleviates Hyperoxia-Induced Bronchopulmonary Dysplasia via Inhibiting Ferroptosis. Redox Biology, 82, Article ID: 103579. [Google Scholar] [CrossRef] [PubMed]
[45] Yang, J., He, Y., Ai, Q., Liu, C., Ruan, Q. and Shi, Y. (2024) Lung-Gut Microbiota and Tryptophan Metabolites Changes in Neonatal Acute Respiratory Distress Syndrome. Journal of Inflammation Research, 17, 3013-3029. [Google Scholar] [CrossRef] [PubMed]
[46] Heumel, S., de Rezende Rodovalho, V., Urien, C., Specque, F., Brito Rodrigues, P., Robil, C., et al. (2024) Shotgun Metagenomics and Systemic Targeted Metabolomics Highlight Indole-3-Propionic Acid as a Protective Gut Microbial Metabolite against Influenza Infection. Gut Microbes, 16, Article ID: 2325067. [Google Scholar] [CrossRef] [PubMed]
[47] Essex, M., Millet Pascual-Leone, B., Löber, U., Kuhring, M., Zhang, B., Brüning, U., et al. (2024) Gut Microbiota Dysbiosis Is Associated with Altered Tryptophan Metabolism and Dysregulated Inflammatory Response in Covid-19. NPJ Biofilms and Microbiomes, 10, Article No. 66. [Google Scholar] [CrossRef] [PubMed]
[48] Yong, C.C., Sakurai, T., Kaneko, H., Horigome, A., Mitsuyama, E., Nakajima, A., et al. (2024) Human Gut-Associated Bifidobacterium Species Salvage Exogenous Indole, a Uremic Toxin Precursor, to Synthesize Indole-3-Lactic Acid via Tryptophan. Gut Microbes, 16, Article ID: 2347728. [Google Scholar] [CrossRef] [PubMed]
[49] Lin, H., Shao, X., Gu, H., Yu, X., He, L., Zhou, J., et al. (2025) Akkermansia muciniphila Ameliorates Doxorubicin-Induced Cardiotoxicity by Regulating PPARα-Dependent Mitochondrial Biogenesis. NPJ Biofilms and Microbiomes, 11, Article No. 86. [Google Scholar] [CrossRef] [PubMed]
[50] Lv, J., Zhang, Y., Liu, S., Wang, R. and Zhao, J. (2025) Gut-Lung Axis in Allergic Asthma: Microbiota-Driven Immune Dysregulation and Therapeutic Strategies. Frontiers in Pharmacology, 16, Article ID: 1617546. [Google Scholar] [CrossRef] [PubMed]
[51] Li, Q., de Oliveira Formiga, R., Puchois, V., Creusot, L., Ahmad, A.H., Amouyal, S., et al. (2025) Microbial Metabolite Indole-3-Propionic Acid Drives Mitochondrial Respiration in CD4+ T Cells to Confer Protection against Intestinal Inflammation. Nature Metabolism, 7, 2510-2530. [Google Scholar] [CrossRef] 
[52] Huang, Z., Hu, Z., Lu, C., Luo, S., Chen, Y., Zhou, Z., et al. (2022) Gut Microbiota-Derived Indole 3-Propionic Acid Partially Activates Aryl Hydrocarbon Receptor to Promote Macrophage Phagocytosis and Attenuate Septic Injury. Frontiers in Cellular and Infection Microbiology, 12, Article ID: 1015386. [Google Scholar] [CrossRef] [PubMed]
[53] Wang, J., Zhu, N., Su, X., Gao, Y. and Yang, R. (2023) Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis. Cells, 12, Article No. 793. [Google Scholar] [CrossRef] [PubMed]
[54] Li, J., Zhang, L., Wu, T., Li, Y., Zhou, X. and Ruan, Z. (2020) Indole-3-Propionic Acid Improved the Intestinal Barrier by Enhancing Epithelial Barrier and Mucus Barrier. Journal of Agricultural and Food Chemistry, 69, 1487-1495. [Google Scholar] [CrossRef] [PubMed]
[55] Zhang, Y., Chen, Y., Xia, J., Li, L., Chang, L., Luo, H., et al. (2024) Rifaximin Ameliorates Influenza a Virus Infection-Induced Lung Barrier Damage by Regulating Gut Microbiota. Applied Microbiology and Biotechnology, 108, Article No. 469. [Google Scholar] [CrossRef] [PubMed]
[56] Alvarado, D.M., Chen, B., Iticovici, M., Thaker, A.I., Dai, N., VanDussen, K.L., et al. (2019) Epithelial Indoleamine 2,3-Dioxygenase 1 Modulates Aryl Hydrocarbon Receptor and Notch Signaling to Increase Differentiation of Secretory Cells and Alter Mucus-Associated Microbiota. Gastroenterology, 157, 1093-1108.e11. [Google Scholar] [CrossRef] [PubMed]
[57] Arboleya, S., Rios-Covian, D., Maillard, F., Langella, P., Gueimonde, M. and Martín, R. (2022) Preterm Delivery: Microbial Dysbiosis, Gut Inflammation and Hyperpermeability. Frontiers in Microbiology, 12, Article ID: 806338. [Google Scholar] [CrossRef] [PubMed]
[58] Lubin, J., Green, J., Maddux, S., Denu, L., Duranova, T., Lanza, M., et al. (2023) Arresting Microbiome Development Limits Immune System Maturation and Resistance to Infection in Mice. Cell Host & Microbe, 31, 554-570.e7. [Google Scholar] [CrossRef] [PubMed]
[59] Yuu, E.Y., Bührer, C., Eckmanns, T., Fulde, M., Herz, M., Kurzai, O., et al. (2024) The Gut Microbiome, Resistome, and Mycobiome in Preterm Newborn Infants and Mouse Pups: Lack of Lasting Effects by Antimicrobial Therapy or Probiotic Prophylaxis. Gut Pathogens, 16, Article No. 27. [Google Scholar] [CrossRef] [PubMed]
[60] Zhao, P., Chen, Y., Zhou, S. and Li, F. (2025) Microbial Modulation of Tryptophan Metabolism Links Gut Microbiota to Disease and Its Treatment. Pharmacological Research, 219, Article ID: 107896. [Google Scholar] [CrossRef] [PubMed]

为你推荐