基于脑–肠轴探索FGIDs肠道菌群与内脏高敏相关性
To Explore the Correlation between Intestinal Flora of FGIDs and Visceral Hypersensitivity Based on Brain-Gut Axis
摘要: 功能性胃肠病(Functional Gastrointestinal Disorder Diseases, FGIDs)是一种常见的胃肠道功能性疾病，目前明确的发病机制并不明确，但是可以确定与内脏的高敏性、胃肠道功能紊乱、肠道黏膜屏障及低度炎症、免疫功能的改变、肠道菌群变化及脑肠轴互动异常等机制有关，是多种因素交叉作用于人体的结果。其中，肠道菌群与内脏高敏性都与FGIDs联系密切，尤其内脏高敏性是FGIDs发生腹痛、腹泻等主观不适症状的主要原因，因此基于脑–肠轴探索FGIDs肠道菌群与内脏高敏性之间的联系，将肠道菌群作为治疗FGIDs的新靶点，对于减轻胃肠道不适症状、提高人类生存质量、改善人类健康具有重要的影响。本文将从羟色胺(5-Hydroxytryptamine, 5-HT)、促肾上腺皮质激素释放因子(Corticotropin Releasing Factor, CRF)、内源性神经营养因子(Brain-Derived Neurotrophic Factor, BDNF)和神经生长因子(Nerve Growth Factor, NGF)四条信号通路来论述FGIDs肠道菌群与内脏高敏性之间的联系。
Abstract: Functional gastrointestinal disorder diseases (FGIDs) is a common gastrointestinal functional disease, the pathogenesis of which is not clear at present. However, it can be confirmed that it is related to the mechanism of hypersensitivity of internal organs, gastrointestinal dysfunction, intestinal mucosal barrier and low inflammation, changes in immune function, changes in intestinal flora and abnormal interaction of brain-gut axis, etc., which is the result of multiple factors acting on the human body. Both intestinal flora and visceral hypersensitivity are closely related to FGIDs, especially visceral hypersensitivity, which is the main cause of subjective discomfort symptoms such as abdominal pain and diarrhea in FGIDs. Therefore, the association between intestinal flora and visceral hypersensitivity of FGIDs is explored based on brain-gut axis, and the intestinal flora is considered as a new target for FGIDs treatment. It has an important influence on alleviating the symptoms of gastrointestinal discomfort, improving the quality of human life and improving human health. In this paper, we will analyze 5-hydroxytryptamine (5-HT), corticotropin releasing factor (CRF), endogenous neurotrophic factor (Brain-Derived Neurotrophic Factor, BDNF) and nerve growth factor (Nerve Growth Factor, model NGF) four signaling pathways to discuss FGIDs between intestinal flora and visceral hypersensitivity sexual contact.
文章引用：焦逸文, 李霏, 范明明. 基于脑–肠轴探索FGIDs肠道菌群与内脏高敏相关性[J]. 临床医学进展, 2025, 15(11): 1188-1196. https://doi.org/10.12677/acm.2025.15113209

参考文献

[1] 韩名媛, 梁吉, 孙忠人, 等. 基于“神经-内分泌-免疫”网络探讨针刺治疗功能性胃肠病机制[J]. 中国中西医结合杂志, 2023, 43(7): 886-890.
[2] Sperber, A.D., Bangdiwala, S.I., Drossman, D.A., et al. (2021) Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology, 160, 99-114.
[3] Drossman, D.A. and Hasler, W.L. (2016) Rome IV—Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology, 150, 1257-1261. [Google Scholar] [CrossRef] [PubMed]
[4] 严巧锋, 侯政昆, 姚思梦, 等. 功能性胃肠病量表在中医药领域的应用现状及策略分析[J]. 世界科学技术: 中医药现代化, 2022, 24(11): 4613-4619.
[5] 梁红亮. 内脏高敏性[J]. 国外医学(消化系疾病分册), 2003(6): 381.
[6] Sperber, A.D., Freud, T., Aziz, I., Palsson, O.S., Drossman, D.A., Dumitrascu, D.L., et al. (2022) Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life. Clinical Gastroenterology and Hepatology, 20, e945-e956. [Google Scholar] [CrossRef] [PubMed]
[7] Feng, B., La, J.H., Schwartz, E.S. and Gebhart, G.F. (2012) Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Neural and Neuro-Immune Mechanisms of Visceral Hypersensitivity in Irritable Bowel Syndrome. American Journal of Physiology-Gastrointestinal and Liver Physiology, 302, G1085-G1098. [Google Scholar] [CrossRef] [PubMed]
[8] Volpicelli, G., Caramello, V., Cardinale, L., Mussa, A., Bar, F. and Frascisco, M.F. (2008) Bedside Ultrasound of the Lung for the Monitoring of Acute Decompensated Heart Failure. The American Journal of Emergency Medicine, 26, 585-591. [Google Scholar] [CrossRef] [PubMed]
[9] Thoua, N.M., Murray, C.D.R., Winchester, W.J., Roy, A.J., Pitcher, M.C.L., Kamm, M.A., et al. (2009) Amitriptyline Modifies the Visceral Hypersensitivity Response to Acute Stress in the Irritable Bowel Syndrome. Alimentary Pharmacology & Therapeutics, 29, 552-560. [Google Scholar] [CrossRef] [PubMed]
[10] Rosen, J.M., Cocjin, J.T., Schurman, J.V., et al. (2014) Visceral Hypersensitivity and Electromechanical Dysfunction as Therapeutic Targets in Pediatric Functional Dyspepsia. World Journal of Gastrointestinal Pharmacology and Therapeutics, 5, Article No. 122. [Google Scholar] [CrossRef] [PubMed]
[11] Camilleri, M. and Boeckxstaens, G. (2017) Dietary and Pharmacological Treatment of Abdominal Pain in IBS. Gut, 66, 966-974. [Google Scholar] [CrossRef] [PubMed]
[12] Hasler, W.L., et al. (2016) Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction Introduction. Gastroenterology, 150, 1257-1261.
[13] Ling, Y., Ding, L., Tian, Z., Pei, L. and Wu, E. (2022) YINDARA-4 Relieves Visceral Hypersensitivity in Irritable Bowel Syndrome Rats via Regulation of Gut Microbiota and Serotonin Levels. Acupuncture and Herbal Medicine, 2, 274-283. [Google Scholar] [CrossRef] 
[14] Barton, J.R., Londregan, A.K., Alexander, T.D., Entezari, A.A., Covarrubias, M. and Waldman, S.A. (2023) Enteroendocrine Cell Regulation of the Gut-Brain Axis. Frontiers in Neuroscience, 17, Article ID: 1272955. [Google Scholar] [CrossRef] [PubMed]
[15] Moore, K., Clarke, A., Kapustin, V., et al. (2010) Evidence for an Alternative Glycolytic Pathway in Rapidly Proliferating Cells.
[16] 常乐, 马佳蕊, 张诗羽, 等. 肠道菌群-天然产物互作在免疫调节中的作用[J/OL]. 微生物学报: 1-18. 2025-11-07.[CrossRef] 
[17] Higgins, G.A., Hong, S. and Wiley, J.W. (2021) The Role of Epigenomic Regulatory Pathways in the Gut-Brain Axis and Visceral Hyperalgesia. Cellular and Molecular Neurobiology, 42, 361-376. [Google Scholar] [CrossRef] [PubMed]
[18] Kabouridis, P.S. and Pachnis, V. (2015) Emerging Roles of Gut Microbiota and the Immune System in the Development of the Enteric Nervous System. Journal of Clinical Investigation, 125, 956-964. [Google Scholar] [CrossRef] [PubMed]
[19] 何力, 杨力, 凌志维, 等. 基于脑肠交互机制探讨肠道微生物调节IBS-D内脏高敏的研究进展[J]. 中国实验方剂学杂志, 2019, 25(11): 224-229.
[20] 常雨, 张艮霜, 张艺川, 等. 中医药治疗功能性消化不良相关信号通路的研究进展[J]. 中国中药杂志, 2023, 48(20): 5397-5403.
[21] 唐艳, 刘志洲, 邓英, 等. 5-羟色胺与Toll样受体及肠道菌群之间关系的研究[J]. 中国微生态学杂志, 2016, 28(12): 1470-1473.
[22] 查天悦, 戴心怡, 徐陆周. 以肠道菌群为靶点治疗腹泻型肠易激综合征的中医研究进展[J]. 江苏预防医学, 2023, 34(3): 309-313.
[23] 冯文林, 伍海涛. 基于短链脂肪酸调控5-HT探讨中医药治疗肠易激综合征作用机制[J]. 吉林中医药, 2019, 39(1): 7-9+23.
[24] 郑煌洪, 吴建平, 王坤. 肠易激综合征患者肠道灌洗液菌群特点[J]. 中国微生态学杂志, 2021, 33(8): 929-932.
[25] Lv, Y.X., et al. (2022) Corticotropin-Releasing Factor Receptor 1 (CRF-R1) Antagonists: Promising Agents to Prevent Visceral Hypersensitivity in Irritable Bowel Syndrome. Peptides, 147, Article ID: 170705
[26] Liu, Y., Wang, Y., Yen, H., Liu, P., Tzeng, W., Tsai, C., et al. (2019) Lactobacillus plantarum PS128 Ameliorated Visceral Hypersensitivity in Rats through the Gut-Brain Axis. Probiotics and Antimicrobial Proteins, 12, 980-993. [Google Scholar] [CrossRef] [PubMed]
[27] Park, H. and Poo, M. (2012) Neurotrophin Regulation of Neural Circuit Development and Function. Nature Reviews Neuroscience, 14, 7-23. [Google Scholar] [CrossRef] [PubMed]
[28] Lima Giacobbo, B., Doorduin, J., Klein, H.C., Dierckx, R.A.J.O., Bromberg, E. and de Vries, E.F.J. (2018) Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation. Molecular Neurobiology, 56, 3295-3312. [Google Scholar] [CrossRef] [PubMed]
[29] Chen, F., Yu, Y., Wang, P., Dong, Y., Wang, T., Zuo, X., et al. (2014) 413 Brain-Derived Neurotrophic Factor Accelerates Gut Motility in Slow-Transit Constipation. Gastroenterology, 146, S-89. [Google Scholar] [CrossRef] 
[30] Fan, F., Tang, Y., Dai, H., Cao, Y., Sun, P., Chen, Y., et al. (2020) Blockade of BDNF Signalling Attenuates Chronic Visceral Hypersensitivity in an IBS‐Like Rat Model. European Journal of Pain, 24, 839-850. [Google Scholar] [CrossRef] [PubMed]
[31] Zhang, Y., Qin, G., Liu, D., Wang, Y. and Yao, S. (2019) Increased Expression of Brain-Derived Neurotrophic Factor Is Correlated with Visceral Hypersensitivity in Patients with Diarrhea-Predominant Irritable Bowel Syndrome. World Journal of Gastroenterology, 25, 269-281. [Google Scholar] [CrossRef] [PubMed]
[32] 赵迎盼, 苏敏, 王凤云, 等. 肠安Ⅰ号方对肠易激综合征内脏高敏感大鼠5-HT信号系统及海马BDNF mRNA表达的影响[J]. 中国中西医结合杂志, 2015, 35(10): 1228-1235.
[33] 焦黛妍, 孙建华. 脑源性神经营养因子在肠道高敏感中的研究进展[J]. 胃肠病学, 2014, 19(2): 121-123.
[34] Bistoletti, M., Caputi, V., Baranzini, N., Marchesi, N., Filpa, V., Marsilio, I., et al. (2019) Antibiotic Treatment-Induced Dysbiosis Differently Affects BDNF and Trkb Expression in the Brain and in the Gut of Juvenile Mice. PLOS ONE, 14, e0212856. [Google Scholar] [CrossRef] [PubMed]
[35] Bercik, P., Verdu, E.F., Foster, J.A., Macri, J., Potter, M., Huang, X., et al. (2010) Chronic Gastrointestinal Inflammation Induces Anxiety-Like Behavior and Alters Central Nervous System Biochemistry in Mice. Gastroenterology, 139, 2102-2112.e1. [Google Scholar] [CrossRef] [PubMed]
[36] 陈采益, 余芝, 纪峰, 等. NGF/PI3K/TRPV1通路介导针刺“上巨虚”调节肠易激综合征慢性内脏痛敏模型大鼠内脏痛[J]. 针刺研究, 2023, 48(10): 1017-1024.
[37] Lu, X. and Zhang, S. (2023) How Tongxie-Yaofang Regulates Intestinal Synaptic Plasticity by Activating Enteric Glial Cells and NGF/TrkA Pathway in Diarrhea-Predominant Irritable Bowel Syndrome Rats. Drug Design, Development and Therapy, 17, 2969-2983. [Google Scholar] [CrossRef] [PubMed]
[38] 庄晓君, 陈旻湖, 熊理守, 等. 肠道微生态参与肠易激综合征发病的相关机制[J]. 胃肠病学, 2017, 22(3): 181-183.
[39] Wong, C.B., Tanaka, A., Kuhara, T. and Xiao, J. (2020) Potential Effects of Indole-3-Lactic Acid, a Metabolite of Human Bifidobacteria, on NGF-Induced Neurite Outgrowth in PC12 Cells. Microorganisms, 8, Article No. 398. [Google Scholar] [CrossRef] [PubMed]
[40] 周彦妮, 陈敏, 杨焱麟, 等. 基于脑肠轴的肠道菌群调控腹泻型肠易激综合征的研究进展[J]. 中华中医药杂志, 2022, 37(3): 1582-1586.
[41] Colucci-D’Amato, L., Speranza, L. and Volpicelli, F. (2020) Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. International Journal of Molecular Sciences, 21, Article No. 7777. [Google Scholar] [CrossRef] [PubMed]
[42] Moloney, R.D., Johnson, A.C., O’Mahony, S.M., Dinan, T.G., Greenwood‐Van Meerveld, B. and Cryan, J.F. (2015) Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neuroscience & Therapeutics, 22, 102-117. [Google Scholar] [CrossRef] [PubMed]
[43] Nozu, T. and Okumura, T. (2022) Pathophysiological Commonality between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-Releasing Factor-Toll-Like Receptor 4-Proinflammatory Cytokine Signaling. Journal of Neurogastroenterology and Motility, 28, 173-184. [Google Scholar] [CrossRef] [PubMed]
[44] Huang, S., Song, Z., Liu, Y., Luo, W., Yin, Q. and Zhang, Y. (2021) BNSTAVGABA-PVNCRF Circuit Regulates Visceral Hypersensitivity Induced by Maternal Separation in Vgat-Cre Mice. Frontiers in Pharmacology, 12, Article ID: 615202. [Google Scholar] [CrossRef] [PubMed]
[45] Mulugeta, M., Taché, Y., Larauche, M., et al. (2017) Brain and Gut CRF Signaling: Biological Actions and Role in the Gastrointestinal Tract. Current Molecular Pharmacology, 11, 51-71.
[46] Wang, Q.-S., et al. (2021) Puerarin from Pueraria lobata Alleviates the Symptoms of Irritable Bowel Syndrome-Diarrhea. Food & Function, 12, 2211-2224.
[47] Zhao, Y., Kang, Y., Zhao, Z., Yang, G., Gao, Y., Gao, L., et al. (2023) Lacticaseibacillus rhamnosus TF318 Prevents Depressive Behavior in Rats by Inhibiting HPA-Axis Hyperactivity and Upregulating BDNF Expression. Neuroscience Letters, 814, Article ID: 137460. [Google Scholar] [CrossRef] [PubMed]
[48] 刘笑彤, 杜晓安, 王文君, 等. 粪菌移植治疗消化道内外疾病的研究进展[J]. 中国微生态学杂志, 2024, 36(11): 1354-1359.
[49] 向雪松, 李晓琴. 后生元科学共识[J/OL]. 卫生研究: 1-22. 2025-11-07.[CrossRef] 
[50] 卢雯, 刘睿娜, 雷璞, 等. 基因工程菌的构建、性能研究及其在疾病诊断和治疗中的应用[J]. 微生物学报, 2023, 63(10): 3758-3772.

为你推荐