【摘要】代谢综合征（MetS）是一类以中心性肥胖、胰岛素抵抗、高血压及血脂异常为特征的复杂代谢性疾病，已成为全球性的公共卫生问题，患病率在成人及肥胖儿童中持续攀升。目前传统治疗以生活方式干预和单一靶点药物为主，面临依从性差、多药联合风险高及管理碎片化等局限。酪酸梭菌是一类重要的产丁酸菌，近年来被证实可通过多靶点机制在代谢综合征防治中发挥关键作用。本文系统综述了代谢综合征的发病机制及其与肠道微生态的关联，重点阐述了酪酸梭菌通过代谢产物丁酸修复肠黏膜屏障、调节肠道菌群结构、抑制炎症及改善胰岛素抵抗等核心环节的作用机理。酪酸梭菌活菌制剂已被国家药品监督管理局批准为绿标OTC药品，为代谢综合征的临床干预提供基于微生态调控的可能性。

【关键词】代谢综合征；酪酸梭菌；基石菌；丁酸；肠黏膜屏障；抑制炎症

1、引言:代谢综合征的概述及流行病学现状

代谢综合征并非单一疾病，而是一种以中心性肥胖、血脂异常、高血压、胰岛素抵抗、氧化应激及慢性炎症等代谢异常为特征的复杂病症[1]。这些代谢异常因素往往聚集出现，共同作用，显著增加个体罹患2型糖尿病和心血管疾病的风险。据统计，代谢综合征患者发生2型糖尿病的风险约为正常人群的5~7倍，发生心血管疾病的风险约为3倍[2]。

代谢综合征已成为全球性的公共卫生流行病。据统计，约39.8%的美国成年人口符合代谢综合征的诊断标准，且患病率随着年龄增长而增加[3]，中国代谢综合征的患病率约为24.2% [4]。儿童与青少年的代谢综合征问题同样不容忽视，一项纳入57项研究、共27,923名肥胖儿童和青少年的荟萃分析显示，代谢综合征的总体患病率为26% [5]。代谢综合征在成人、儿童及不同地区人群中均呈现高发态势，已成为严重威胁人类健康的重大公共卫生问题。

代谢综合征的影响不仅限于个人健康;它给医疗系统带来了巨大的经济负担。管理MetS及其并发症，如心血管疾病和糖尿病，需要大量的医疗资源。这包括与医疗治疗、住院以及因疾病导致的生产力损失相关的费用[6]。

2、代谢综合征的发病机制

代谢综合征的发生与发展是多因素、多通路共同参与的复杂病理生理过程，其核心机制可概括为肠道屏障损伤—肠道菌群失调—慢性低度炎症—胰岛素抵抗—异位脂肪沉积的逐级放大级联反应[7][8]。在高脂高糖饮食、久坐、肥胖及遗传易感性等多种危险因素的长期作用下，肠上皮细胞间紧密连接蛋白（如 occludin、claudin、ZO1）的表达与分布发生异常，导致肠道屏障完整性破坏、肠道通透性增高，即形成 “肠漏” 状态[7][9]。肠道屏障受损使得肠道内的脂多糖、细菌碎片、代谢毒素及部分抗原物质大量易位进入门脉循环与体循环，进一步诱发并加剧肠道菌群失衡，表现为有益共生菌减少、条件致病菌过度增殖、短链脂肪酸等保护性代谢物生成不足[7]。菌群失衡与毒素易位共同激活机体固有免疫通路，诱导全身慢性低度炎症的发生与持续，释放 TNFα、IL6、IFNγ 等促炎因子[10][11]。这些炎症信号通过干扰胰岛素受体底物及下游 PI3K/Akt 信号通路，抑制胰岛素介导的葡萄糖摄取与利用，最终诱发胰岛素抵抗这一代谢综合征的核心病理环节[7][12]。胰岛素抵抗进一步扰乱全身糖脂代谢平衡，促使脂肪分解异常增加、游离脂肪酸水平升高，并导致脂质在肝脏、骨骼肌、心脏及胰腺等非脂肪组织异位沉积，形成恶性循环，最终推动中心性肥胖、糖调节受损、血脂紊乱、高血压等一系列代谢异常的发生与进展[13][14]。

3、传统治疗代谢综合征的局限性

目前代谢综合征的临床治疗仅限于生活方式和针对单一危险因素的药物治疗[15]。代谢综合征涉及多系统、多器官的复杂病理生理过程，而现有临床指南多从单一疾病视角制定，导致患者管理在专科之间呈现碎片化，治疗方案往往以多药联合形式出现，不仅增加药物相互作用风险和累积不良事件，还降低了患者的治疗依从性[16][17]。因此，亟需找到能够同时作用于多个病理环节、具有良好安全性和依从性的新型干预策略。

4、酪酸梭菌的动物研究及临床应用

近年来，酪酸梭菌在代谢综合征防治中的作用得到广泛研究。2026年01月，美国詹姆斯麦迪逊大学Bisi T. Velayudhan团队发表综述，指出以酪酸梭菌为代表的产丁酸菌是肠道“基石菌”，在保护肠道屏障、调控免疫、维持健康中发挥核心作用[18]。

多项动物研究表明，酪酸梭菌对代谢综合征相关指标显示出明确的改善作用。对高脂饮食诱导的肥胖小鼠给予酪丁酸梭菌干预6周后发现，干预组小鼠肝脏重量显著降低，肝脏甘油三酯、总胆固醇和非酯化脂肪酸水平均明显下降[19]。在链脲佐菌素诱导的糖尿病大鼠模型中证实，酪酸梭菌干预21天后，随机血糖水平显著降低，同时肠道细菌载量明显增加[20]。在高脂饮食诱导的肥胖小鼠中发现，酪酸梭菌能够有效地降低体重增长，改善糖脂代谢异常及脂肪肝病理特征，并抑制机会致病菌增殖[21]。

在临床应用方面，Song等（2025）对100例精神分裂症合并代谢综合征患者进行的临床研究发现，接受酪酸梭菌CGMCC 0313-1联合生活方式干预12周后，观察组较单纯生活方式干预组在氧化应激改善和总体疗效方面表现出显著优势，同时肥胖指标、血糖水平、血脂谱、血压及阳性和阴性症状量表评分的改善均更为明显。该研究提示，酪酸梭菌干预有助于改善精神分裂症患者代谢综合征的临床管理，且耐受性良好[22]。

5、酪酸梭菌防治代谢综合征的机制机理

5.1 修复肠粘膜屏障

酪酸梭菌通过其代谢产物丁酸修复肠道屏障功能[23][24]。丁酸是结肠上皮细胞的主要能量来源，通过单羧酸转运蛋白进入细胞后在线粒体中进行β-氧化，为细胞提供能量[24][25]。这一过程消耗氧气，稳定缺氧诱导因子-1α，后者上调紧密连接蛋白的表达，加固肠道机械屏障[24][25]。同时，丁酸通过促进黏蛋白2的合成与分泌，增强肠道化学屏障功能[26]。丁酸还可通过诱导调节性T细胞分化，调节肠道免疫屏障，维持免疫稳态[27]。此外，丁酸通过抑制病原菌生长、促进有益菌增殖，强化肠道生物屏障[28]。研究证实，补充酪酸梭菌可显著降低肠道通透性，减少脂多糖渗漏，从而阻断代谢性内毒素血症的发生[29]。

5.2 恢复肠道菌群平衡

酪酸梭菌作为产丁酸菌的代表菌种，补充后可有效增加肠道菌群的多样性和丰度[30]。酪酸梭菌产生的丁酸可酸化肠道微环境，抑制有害菌生长，促进有益菌的繁殖，重建健康的肠道生态系统[31]。研究显示，高脂饮食诱导的菌群失衡修复作用显著，不仅能提升小鼠肠道有益菌数量与菌群多样性，且高剂量干预组的菌群整体构成，已和正常饮食的健康小鼠非常接近，还能显著增加肠道内丁酸、乙酸、丙酸等短链脂肪酸浓度[30]。这些代谢产物可调节肠道 pH 值，抑制有害菌增殖，同时为有益菌提供能量，形成菌群平衡正向循环[30][31]。

5.3 抑制炎症反应

丁酸作为一种内源性的组蛋白去乙酰化酶（HDAC）抑制剂，能够通过表观遗传学机制调节基因表达，促进抗炎功能[32]。它能增加Foxp3基因座上组蛋白的乙酰化水平，从而促进调节性T细胞（Tregs）的产生[32]。Tregs是免疫系统中的“维和部队”，能够抑制过度的炎症反应，维持免疫耐受[32]。通过这种机制，丁酸和酪酸梭菌能够有效抑制全身性炎症[33][34][35]。例如，在小儿原发性肾病综合征中，酪酸梭菌通过调节Th17/Tregs平衡减轻炎症[33]。在急性胰腺炎中，酪酸梭菌通过调节AMPK/NF-κB信号通路减轻炎症[34]。纳米涂层酪酸梭菌也能在肠道和肠外器官产生抗炎和组织修复作用[36]。

5.4 改善胰岛素抵抗与代谢信号

酪酸梭菌及其丁酸对代谢综合征的直接影响还体现在改善脂肪代谢和胰岛素敏感性方面[37][38]。2025年发表于Microbiological Research的研究阐明，酪酸梭菌NCU-27通过调节丁酸代谢，经肠-肝轴靶向抑制肝细胞中mTORC1的表达，激活IRS1/AKT通路，增强葡萄糖摄取和糖原合成，抑制糖异生[39]。该研究发现，酪酸梭菌干预后，模型大鼠的空腹血糖、空腹胰岛素水平和HOMA-IR指数均显著降低，葡萄糖耐量和肝糖原含量明显改善。研究表明，酪酸梭菌可通过抑制白色脂肪细胞生成、增加脂肪组织调节性T细胞数量来抑制脂肪沉积，改善脂质代谢[38]。在饮食诱导的肥胖小鼠模型中，酪酸梭菌和丁酸均能有效预防肥胖和代谢紊乱[38]。

6、总结

综上所述，酪酸梭菌能够通过产生丁酸，修复肠粘膜屏障、恢复菌群平衡、抑制炎症、改善胰岛素抵抗与代谢信号，在代谢综合征的防治中发挥基石作用。目前已有动物实验及临床研究指出了酪酸梭菌在代谢综合征治疗中的关键作用[19][20][21][22]。医用微生态制品开发国家地方联合工程研究中心崔云龙教授团队在国家863计划的支持下，成功攻克高活性菌株选育、高密度发酵、三层微囊化制剂工艺技术难关，自主创研了酪酸梭菌（CGMCC0313-1）活菌制剂并实现产业化，获得了中美双专利授权。目前，酪酸梭菌活菌制剂已被国家药品监督管理局批准为绿标OTC产品[40][41]，是成熟、安全、有效的药准字药品，为临床代谢综合征的防治提供了新的可能性。

参考文献:

[1] Hamooya, B. M., Siame, L., Muchaili, L., Masenga, S. K., & Kirabo, A. (2025). Metabolic syndrome: epidemiology, mechanisms, and current therapeutic approaches. Frontiers in nutrition, 12, 1661603. https://doi.org/10.3389/fnut.2025.1661603

[2] Giangregorio, F., Mosconi, E., Debellis, M. G., Provini, S., Esposito, C., Garolfi, M., Oraka, S., Kaloudi, O., Mustafazade, G., Marín-Baselga, R., & Tung-Chen, Y. (2024). A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches. Journal of Clinical Medicine, 13(19), 5880. https://doi.org/10.3390/jcm13195880

[3] Liang, X., Or, B., Tsoi, M. F., Cheung, C. L., & Cheung, B. M. Y. (2023). Prevalence of metabolic syndrome in the United States National Health and Nutrition Examination Survey 2011-18. Postgraduate medical journal, 99(1175), 985–992. https://doi.org/10.1093/postmj/qgad008

[4] Li, Y., Zhao, L., Yu, D., Wang, Z., & Ding, G. (2018). Metabolic syndrome prevalence and its risk factors among adults in China: A nationally representative cross-sectional study. PloS one, 13(6), e0199293. https://doi.org/10.1371/journal.pone.0199293

[5] Wentzel A, Mabhida SE, Ndlovu M, et al. Prevalence of metabolic syndrome in children and adolescents with obesity: a systematic review and meta-analysis. Obesity (Silver Spring). 2025;33(1):12-32. DOI: 10.1002/oby.24159

[6] Scholze, J., Alegria, E., Ferri, C., Langham, S., Stevens, W., Jeffries, D., & Uhl-Hochgraeber, K. (2010). Epidemiological and economic burden of metabolic syndrome and its consequences in patients with hypertension in Germany, Spain and Italy; a prevalence-based model. BMC public health, 10, 529. https://doi.org/10.1186/1471-2458-10-529

[7] Yang-Jensen, S. K., Nägele, N. S., & Jensen, B. A. H. (2025). From gut to blood: barrier dysfunction as a driver of systemic low-grade inflammation in cardiometabolic disease. American journal of physiology. Cell physiology, 329(6), C1723–C1741. https://doi.org/10.1152/ajpcell.00704.2025

[8] Jing, M., & Jiang, Y. (2025). Microbiome-mediated crosstalk between T2DM and MASLD: a translational review focused on function. Frontiers in endocrinology, 16, 1677175. https://doi.org/10.3389/fendo.2025.1677175

[9] Mak, K. M., Ding, S. Y., & Jain, C. (2025). Ethanol, acetaldehyde, lipopolysaccharide, and neutrophil extracellular traps: four-pronged attack on gut epithelial barrier in alcohol use disorder. Anatomical record (Hoboken, N.J. : 2007), 10.1002/ar.70084. Advance online publication. https://doi.org/10.1002/ar.70084

[10] Ouyang, J., Lu, W., Fan, Y., Jiang, Z., Du, Q., & Liu, D. (2025). Adipose Tissue Metabolic Inflammation: A Key Driver of Cardiovascular Disease Pathogenesis and Underlying Mechanisms. In Advances in Metabolic Syndrome [Working Title]. IntechOpen. https://doi.org/10.5772/intechopen.1012954

[11] Morozova, N., Saito, H., Yasin, A., Correia, D., König, M., & Dubois, C. (2025). Biochemical markers of metabolic syndrome: From lipid profiles to inflammatory cytokines. Hong Kong Medical Journal, 62(2025).

[12] Zarkesh, M., Saba, R., Aghazadeh, H., Teymoori, F., Akbarzadeh, M., Asghari, G., Montazeri, M., Ghasemi, A., Yuzbashian, E., Zadeh-Vakili, A., Hedayati, M., & Khalaj, A. (2025). The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study. Scientific reports, 15(1), 20592. https://doi.org/10.1038/s41598-025-05233-4

[13] Janssen, J. A. M. J. L. (2024). The Causal Role of Ectopic Fat Deposition in the Pathogenesis of Metabolic Syndrome. International Journal of Molecular Sciences, 25(24), 13238. https://doi.org/10.3390/ijms252413238

[14] The Role of Gut Microbiota in Metabolic Syndrome: Mechanistic Insights and Therapeutic Perspectives — A Narrative Review”. (2026). African Journal of Biomedical Research, 29(1S), 328-335. https://doi.org/10.53555/AJBR.v29i1S.9372

[15] Zheng, L., Zeng, A., Liu, L. et al. Metabolic syndrome: molecular mechanisms and therapeutic interventions. Mol Biomed 6, 59 (2025). https://doi.org/10.1186/s43556-025-00303-5

[16] Davis G, Kim D, Jun M ...Implementation Barriers to Evidence-Based Cardiovascular-Kidney-Metabolic Syndrome Management.Heart, Lung and Circulation, 2025; 34, 1060-1068

[17] Dong H, Chang L, Tian T, Shi R, Yu K, Wang C, Liu Z, Jin Q, Wang J, He T, Chen H, Shao X and Deng Y (2025) Mechanism-guided pharmacotherapy for cardiometabolic multimorbidity: from pathophysiology to phenotype-prioritized treatment. Front. Endocrinol. 16:1724965. doi: 10.3389/fendo.2025.1724965

[18] Snodgrass JL,Velayudhan BT. Butyrate-Producing Bacteria as a Keystone Species of the Gut Microbiome: A Systemic Review of Dietary Impact on Gut-Brain and Host Health. Int J Mol Sci. 2026;27 (3):. doi:10.3390/ijms27031289.

[19] Luo, Y., Jin, Y., Wang, H., Wang, G., Lin, Y., Chen, H., Li, X., & Wang, M. (2024). Effects of Clostridium tyrobutyricum on Lipid Metabolism, Intestinal Barrier Function, and Gut Microbiota in Obese Mice Induced by High-Fat Diet. Nutrients, 16(4), 493. https://doi.org/10.3390/nu16040493

[20] Tayyib, H. M. U., Ali, A., Jabeen, S., Habib-Ur-Rehman, Kamran, H., Bajaber, M. A., Usman, M., & Zhang, X. (2024). Restoration of gut dysbiosis through Clostridium butyricum and magnesium possibly balance blood glucose levels: an experimental study. BMC microbiology, 24(1), 105. https://doi.org/10.1186/s12866-024-03218-3

[21] Qiao, S., Wang, T., Sun, J., Han, J., Dai, H., Du, M., Yang, L., Guo, C. J., Liu, C., Liu, S. J., & Liu, H. (2025). Cross-feeding-based rational design of a probiotic combination of Bacterides xylanisolvens and Clostridium butyricum therapy for metabolic diseases. Gut microbes, 17(1), 2489765. https://doi.org/10.1080/19490976.2025.2489765

[22] Song, L., Zhang, Z., Zheng, W., Wang, Y., & Zhang, Y. (2025). Clostridium butyricum CGMCC 0313.1 improves clinical outcomes of metabolic syndrome in schizophrenic patients. American journal of translational research, 17(6), 4399–4408. https://doi.org/10.62347/DNIL9369

[23] Qian S, Li S, Ye K, Lu S, Sha X, Zhang D, Xu Z, Song X and Li R (2026) The role of Clostridium butyricum and its metabolites in modulating gut mucosal immunity: implications for viral infections and inflammatory diseases. Front. Immunol. 17:1763817. doi: 10.3389/fimmu.2026.1763817

[24] Ornelas, A., Countess, J.A., Kim, J.Y. and Colgan, S.P. (2026), Modifying microbially derived short chain fatty acids to promote health. J Physiol, 604: 116-128. https://doi.org/10.1113/JP287585

[25] Yin, ,Zhou, ,Yang, ,Ren, ,Qiu, ,Xu, ,Xiao, , & Yang, (2020). Mutual regulation between butyrate and hypoxia-inducible factor-1α in epithelial cell promotes expression of tight junction proteins. Cell biology international, 44 (6), 1405-1414. https://doi.org/10.1002/cbin.11336

[26] Liang, L., Liu, L., Zhou, W., Yang, C., Mai, G., Li, H., & Chen, Y. (2022). Gut microbiota-derived butyrate regulates gut mucus barrier repair by activating the macrophage/WNT/ERK signaling pathway. Clinical science (London, England : 1979), 136(4), 291–307. https://doi.org/10.1042/CS20210778

[27] Arpaia, N., Campbell, C., Fan, X. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013). https://doi.org/10.1038/nature12726

[28] Schulthess, J., Pandey, S., Capitani, M., Rue-Albrecht, K. C., Arnold, I., Franchini, F., Chomka, A., Ilott, N. E., Johnston, D. G. W., Pires, E., McCullagh, J., Sansom, S. N., Arancibia-Cárcamo, C. V., Uhlig, H. H., & Powrie, F. (2019). The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. Immunity, 50(2), 432–445.e7.

[29] Wang, T., Fu, J., Xiao, X., Lu, Z., Wang, F., Jin, M., Wang, Y., & Zong, X. (2021). CBP22, a Novel Bacteriocin Isolated from Clostridium butyricum ZJU-F1, Protects against LPS-Induced Intestinal Injury through Maintaining the Tight Junction Complex. Mediators of inflammation, 2021, 8032125. https://doi.org/10.1155/2021/8032125

[30] Meng Y, Bai L, Meng J, Ding C, Xi J. 2025. The anti-obesity effects of Clostridium butyricum B-3 and its impact on gut microbiota. Appl Environ Microbiol 91:e01152-25.https://doi.org/10.1128/aem.01152-25

[31] Pang, Y., Xu, X., Li, D. et al. Impact of Clostridium butyricum HADIG-CB003 dietary supplementation on the gut microbiota of Kunming mice. Appl Microbiol Biotechnol 109, 237 (2025). https://doi.org/10.1007/s00253-025-13546-7

[32] Zhao M, Chu J, Feng S, et al. Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review. Biomedicine & Pharmacotherapy, 2023, 165: 114984. DOI: 10.1016/j.biopha.2023.114984

[33] Li T, Ma X, Wang T, et al. Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis. BMC Microbiology, 2024, 24(1): 1-13. DOI: 10.1186/s12866-024-03242-3

[34] Wen B, Huang Y, Deng G, et al. Gut microbiota analysis and LC-MS-based metabolomics to investigate AMPK/NF-κB regulated by Clostridium butyricum in the treatment of acute pancreatitis. Journal of Translational Medicine, 22(1): 1-15. DOI: 10.1186/s12967-024-05764-w

[35] Zhao J, Jiang L, He W, et al. Clostridium butyricum, a future star in sepsis treatment. Frontiers in Cellular and Infection Microbiology, 2024, 14: 1484371. DOI: 10.3389/fcimb.2024.1484371

[36] Deng B, Lin S, Wang Y, et al. Hyaluronic Acid‐Nanocoated Bacteria Generate an Anti‐Inflammatory Tissue‐Repair Effect in Impaired Gut and Extraintestinal Organs. Advanced Materials, 2024, 36(50): 2412783. DOI: 10.1002/adma.202412783

[37] Sooragonda B G, Thakur P, Moganti R, et al. Systematic Review of the Effectiveness of Common Probiotic Strains: Streptococcus faecalis, Clostridium butyricum, Bacillus mesentericus, and Lactobacillus sporogenes in the Management of Diabetes. Journal of Diabetology, 2025, 14(1): 1. DOI: 10.4103/jod.jod_157_24

[38] Li, H., Jia, Y., Weng, D., Ju, Z., Zhao, Y., Liu, S., Liu, Y., Song, M., Cui, L., Sun, S., & Lin, H. (2022). Clostridium butyricum Inhibits Fat Deposition via Increasing the Frequency of Adipose Tissue-Resident Regulatory T Cells. Molecular nutrition & food research, 66(12), e2100884. https://doi.org/10.1002/mnfr.202100884

[39] He, Z., Xiong, H., Cai, Y., Chen, W., Shi, M., Liu, L., Wu, K., Deng, X., Deng, X., & Chen, T. (2025). Clostridium butyricum ameliorates post-gastrectomy insulin resistance by regulating the mTORC1 signaling pathway through the gut-liver axis. Microbiological Research, 297, 128154. https://doi.org/10.1016/j.micres.2025.128154

[40] https://www.nmpa.gov.cn/datasearch/search-info.html?nmpa=aWQ9MjJmNGYzNWJmMGVmYzBjMTIzMmIxNjU0MmQwOGU0ZmYmaXRlbUlkPWZmODA4MDgxODNjYWQ3NTAwMTg0MDg4MWY4NDgxNzlm.

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