|
|
下一代益生菌的作用机制及临床应用进展
|
Abstract:
下一代益生菌(NGPs)作为新型微生物疗法，因其更强的肠道定植能力和多样的健康益处，正在引领健康干预领域的变革。本文系统综述了嗜黏蛋白阿克曼氏菌、长双歧杆菌1714、克里斯滕森菌和普拉氏栖粪杆菌等主要NGPs的作用机制，并探讨了NGPs在代谢性疾病、肿瘤、肠道疾病和其他疾病中的临床应用进展。研究发现，NGPs通过调节肠道微生物群落结构、增强免疫功能、改善肠道屏障完整性等多种机制，展现出对多种疾病的显著治疗潜力。例如，嗜黏蛋白阿克曼氏菌通过激活脂质氧化和胆汁酸代谢改善代谢功能障碍；长双歧杆菌1714可能通过调节神经营养因子水平减轻压力；克里斯滕森菌通过调节炎症信号通路和短链脂肪酸水平发挥抗肥胖作用；普拉氏栖粪杆菌产生丁酸盐从而发挥抗炎作用。尽管NGPs的研究取得了显著进展，但仍需通过大规模临床试验进一步验证其安全性和有效性，并结合基因编辑技术开发个性化制剂，以推动精准医疗的发展。
Next-generation probiotics (NGPs), as novel microbial therapeutics, are leading the change in the field of health interventions due to their enhanced intestinal colonisation and diverse health benefits. In this paper, we systematically review the mechanism of action of major NGPs, such as Akkermansia muciniphila, Bifidobacterium longum 1714, Christensenella minuta, and Faecalibacterium prausnitzii, and discuss the advances in the clinical application of NGPs in metabolic disorders, oncology, intestinal disorders, and other diseases. It was found that NGPs exhibit significant therapeutic potential for a wide range of diseases through a variety of mechanisms, such as regulating the structure of the intestinal microbial community, enhancing immune function, and improving the integrity of the intestinal barrier. For example, Akkermansia muciniphila improves metabolic dysfunction by activating lipid oxidation and bile acid metabolism; Bifidobacterium longum 1714 reduces stress by regulating the level of neurotrophic factors; Christensenella minuta exerts an anti-obesity effect by regulating inflammatory signalling pathways and the level of short-chain fatty acids; and Faecalibacterium prausnitzii exerts an anti-inflammatory effect by producing butyrate. Despite the significant progress in the research of NGPs, there is still a need to further validate their safety and efficacy through large-scale clinical trials and to develop personalised agents in combination with gene editing technologies to promote the development of precision medicine.
| [1] | 焦帅, 付域泽, 张乃锋. 下一代益生菌作用机制及功能特性研究进展[J]. 动物营养学报, 2022, 34(8): 4836-4846. |
| [2] | Pesce, M., Seguella, L., Del Re, A., Lu, J., Palenca, I., Corpetti, C., et al. (2022) Next-Generation Probiotics for Inflammatory Bowel Disease. International Journal of Molecular Sciences, 23, Article 5466. https://doi.org/10.3390/ijms23105466 |
| [3] | 杨姗姗, 李彤, 乌日娜, 等. 下一代益生菌对肥胖人群肠道微生物调控作用的研究进展[J]. 中国食品学报, 2021, 21(4): 356-363. |
| [4] | Cani, P.D., Depommier, C., Derrien, M., Everard, A. and de Vos, W.M. (2022) Author Correction: Akkermansia muciniphila: Paradigm for Next-Generation Beneficial Microorganisms. Nature Reviews Gastroenterology & Hepatology, 19, 682-682. https://doi.org/10.1038/s41575-022-00650-6 |
| [5] | Rao, Y., Kuang, Z., Li, C., Guo, S., Xu, Y., Zhao, D., et al. (2021) Gut Akkermansia muciniphila Ameliorates Metabolic Dysfunction-Associated Fatty Liver Disease by Regulating the Metabolism of L-Aspartate via Gut-Liver Axis. Gut Microbes, 13, Article 1927633. https://doi.org/10.1080/19490976.2021.1927633 |
| [6] | Kaźmierczak-Siedlecka, K., Skonieczna-Żydecka, K., Hupp, T., Duchnowska, R., Marek-Trzonkowska, N. and Połom, K. (2022) Next-Generation Probiotics—Do They Open New Therapeutic Strategies for Cancer Patients? Gut Microbes, 14, Article 2035659. https://doi.org/10.1080/19490976.2022.2035659 |
| [7] | Allen, A.P., Hutch, W., Borre, Y.E., Kennedy, P.J., Temko, A., Boylan, G., et al. (2016) Bifidobacterium longum 1714 as a Translational Psychobiotic: Modulation of Stress, Electrophysiology and Neurocognition in Healthy Volunteers. Translational Psychiatry, 6, e939-e939. https://doi.org/10.1038/tp.2016.191 |
| [8] | Kropp, C., Tambosco, K., Chadi, S., Langella, P., Claus, S.P. and Martin, R. (2024) Christensenella minuta Protects and Restores Intestinal Barrier in a Colitis Mouse Model by Regulating Inflammation. npj Biofilms and Microbiomes, 10, Article No. 88. https://doi.org/10.1038/s41522-024-00540-6 |
| [9] | Ang, W., Law, J.W., Letchumanan, V., Hong, K.W., Wong, S.H., Ab Mutalib, N.S., et al. (2023) A Keystone Gut Bacterium Christensenella minuta—A Potential Biotherapeutic Agent for Obesity and Associated Metabolic Diseases. Foods, 12, Article 2485. https://doi.org/10.3390/foods12132485 |
| [10] | Ignatyeva, O., Tolyneva, D., Kovalyov, A., Matkava, L., Terekhov, M., Kashtanova, D., et al. (2024) Christensenella minuta, a New Candidate Next-Generation Probiotic: Current Evidence and Future Trajectories. Frontiers in Microbiology, 14, Article 1241259. https://doi.org/10.3389/fmicb.2023.1241259 |
| [11] | Li, H., Xu, M., Xu, X., Tang, Y., Jiang, H., Li, L., et al. (2022) Faecalibacterium prausnitzii Attenuates CKD via Butyrate-Renal GPR43 Axis. Circulation Research, 131, e120-e134. https://doi.org/10.1161/circresaha.122.320184 |
| [12] | Ma, J., Sun, L., Liu, Y., Ren, H., Shen, Y., Bi, F., et al. (2020) Alter between Gut Bacteria and Blood Metabolites and the Anti-Tumor Effects of Faecalibacterium prausnitzii in Breast Cancer. BMC Microbiology, 20, 1-19. https://doi.org/10.1186/s12866-020-01739-1 |
| [13] | Martín, R., Rios-Covian, D., Huillet, E., Auger, S., Khazaal, S., Bermúdez-Humarán, L.G., et al. (2023) Faecalibacterium: A Bacterial Genus with Promising Human Health Applications. FEMS Microbiology Reviews, 47, fuad039. https://doi.org/10.1093/femsre/fuad039 |
| [14] | Zhai, Q., Feng, S., Arjan, N. and Chen, W. (2018) A Next Generation Probiotic, Akkermansia muciniphila. Critical Reviews in Food Science and Nutrition, 59, 3227-3236. https://doi.org/10.1080/10408398.2018.1517725 |
| [15] | Martín, R., Miquel, S., Benevides, L., Bridonneau, C., Robert, V., Hudault, S., et al. (2017) Functional Characterization of Novel Faecalibacterium prausnitzii Strains Isolated from Healthy Volunteers: A Step Forward in the Use of F. Prausnitzii as a Next-Generation Probiotic. Frontiers in Microbiology, 8, Article 1226. https://doi.org/10.3389/fmicb.2017.01226 |
| [16] | Vallianou, N.G., Kounatidis, D., Tsilingiris, D., Panagopoulos, F., Christodoulatos, G.S., Evangelopoulos, A., et al. (2023) The Role of Next-Generation Probiotics in Obesity and Obesity-Associated Disorders: Current Knowledge and Future Perspectives. International Journal of Molecular Sciences, 24, Article 6755. https://doi.org/10.3390/ijms24076755 |
| [17] | Torres-Sánchez, A., Ruiz-Rodríguez, A., Ortiz, P., Moreno, M.A., Ampatzoglou, A., Gruszecka-Kosowska, A., et al. (2022) Exploring Next Generation Probiotics for Metabolic and Microbiota Dysbiosis Linked to Xenobiotic Exposure: Holistic Approach. International Journal of Molecular Sciences, 23, Article 12917. https://doi.org/10.3390/ijms232112917 |
| [18] | Zheng, M., Ye, H., Yang, X., Shen, L., Dang, X., Liu, X., et al. (2024) Probiotic Clostridium butyricum Ameliorates Cognitive Impairment in Obesity via the Microbiota-Gut-Brain Axis. Brain, Behavior, and Immunity, 115, 565-587. https://doi.org/10.1016/j.bbi.2023.11.016 |
| [19] | Gong, J., Zhang, Q., Hu, R., Yang, X., Fang, C., Yao, L., et al. (2024) Effects of Prevotella copri on Insulin, Gut Microbiota and Bile Acids. Gut Microbes, 16, Article 2340487. https://doi.org/10.1080/19490976.2024.2340487 |
| [20] | Wu, T., Lin, C., Chang, C., Lin, T., Martel, J., Ko, Y., et al. (2018) Gut Commensal Parabacteroides goldsteinii Plays a Predominant Role in the Anti-Obesity Effects of Polysaccharides Isolated from Hirsutella Sinensis. Gut, 68, 248-262. https://doi.org/10.1136/gutjnl-2017-315458 |
| [21] | 潘意, 林小力, 谭丹婷, 施晶晶, 梁巧奕, 姚秀, 罗善山, 左红群. 益生菌联合耳穴干预治疗对促进胃癌患者术后胃肠功能恢复的临床研究[J]. 现代医学与健康研究电子杂志, 2025, 9(2): 134-138. |
| [22] | Tan-Lim, C.S.C. and Esteban-Ipac, N.A.R. (2025) Systematic Review and Meta-Analysis on Probiotics as Treatment for Food Allergies among Pediatric Patients: A 2024 Update. Pediatric Allergy and Immunology, 36, e70028. https://doi.org/10.1111/pai.70028 |
| [23] | Omprakash, O., Kumar, R., Singh, P., Devi, P., Malik, A. and Mahal, N. (2024) Quantitative Distribution Profile of Cadmium and Lead in Different Organs of Rats and Mitigation of Their Accumulation through Probiotic Treatment. Gut Microbes Reports, 1, Article 2313299. https://doi.org/10.1080/29933935.2024.2313299 |
| [24] | Suez, J., Zmora, N. and Elinav, E. (2019) Probiotics in the Next-Generation Sequencing Era. Gut Microbes, 11, 77-93. https://doi.org/10.1080/19490976.2019.1586039 |
| [25] | Jan, T., Negi, R., Sharma, B., Kumar, S., Singh, S., Rai, A.K., et al. (2024) Next Generation Probiotics for Human Health: An Emerging Perspective. Heliyon, 10, e35980. https://doi.org/10.1016/j.heliyon.2024.e35980 |
| [26] | Al-Fakhrany, O.M. and Elekhnawy, E. (2024) Next-Generation Probiotics: The Upcoming Biotherapeutics. Molecular Biology Reports, 51, Article No. 505. https://doi.org/10.1007/s11033-024-09398-5 |
| [27] | Rezaei, Z., Salari, A., Khanzadi, S., Rhim, J. and Shamloo, E. (2023) Preparation of Milk-Based Probiotic Lactic Acid Bacteria Biofilms: A New Generation of Probiotics. Food Science & Nutrition, 11, 2915-2924. https://doi.org/10.1002/fsn3.3273 |
| [28] | 李慧玲, 刘碧晴, 冯英楠, 胡欣, 张兰, 董宪喆. 靶向肠道菌群改善肿瘤免疫治疗耐药策略的研究进展[J]. 药学学报, 2025, 60(2): 260-268. |
| [29] | Horvath, A., Haller, R., Feldbacher, N., Habisch, H., Žukauskaitė, K., Madl, T., et al. (2024) Probiotic Therapy of Gastrointestinal Symptoms during COVID-19 Infection: A Randomized, Double-Blind, Placebo-Controlled, Remote Study. Nutrients, 16, Article 3970. https://doi.org/10.3390/nu16223970 |
| [30] | Goossens, D., Jonkers, D., Russel, M., Stobberingh, E., Van Den Bogaard, A. and StockbrÜgger, R. (2003) The Effect of Lactobacillus plantarum 299v on the Bacterial Composition and Metabolic Activity in Faeces of Healthy Volunteers: A Placebo-Controlled Study on the Onset and Duration of Effects. Alimentary Pharmacology & Therapeutics, 18, 495-505. https://doi.org/10.1046/j.1365-2036.2003.01708.x |
| [31] | Zhang, W., Zhu, B., Xu, J., Liu, Y., Qiu, E., Li, Z., et al. (2018) Bacteroides Fragilis Protects against Antibiotic-Associated Diarrhea in Rats by Modulating Intestinal Defenses. Frontiers in Immunology, 9, Article 1040. https://doi.org/10.3389/fimmu.2018.01040 |
| [32] | Gao, K., Liu, L., Dou, X., Wang, C., Liu, J., Zhang, W., et al. (2016) Doses Lactobacillus reuteri Depend on Adhesive Ability to Modulate the Intestinal Immune Response and Metabolism in Mice Challenged with Lipopolysaccharide. Scientific Reports, 6, Article No. 28332. https://doi.org/10.1038/srep28332 |
| [33] | Liu, J., Kong, I.I., Zhang, G., Jayakody, L.N., Kim, H., Xia, P., et al. (2016) Metabolic Engineering of Probiotic Saccharomyces boulardii. Applied and Environmental Microbiology, 82, 2280-2287. https://doi.org/10.1128/aem.00057-16 |
| [34] | Rodrigues, V.F., Elias-Oliveira, J., Pereira, Í.S., Pereira, J.A., Barbosa, S.C., Machado, M.S.G., et al. (2022) Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Frontiers in Immunology, 13, Article 934695. https://doi.org/10.3389/fimmu.2022.934695 |
| [35] | Hoang, T.K., He, B., Wang, T., Tran, D.Q., Rhoads, J.M. and Liu, Y. (2018) Protective Effect of Lactobacillus reuteri DSM 17938 against Experimental Necrotizing Enterocolitis Is Mediated by Toll-Like Receptor 2. American Journal of Physiology-Gastrointestinal and Liver Physiology, 315, G231-G240. https://doi.org/10.1152/ajpgi.00084.2017 |
| [36] | Mohebali, N., Weigel, M., Hain, T., Sütel, M., Bull, J., Kreikemeyer, B., et al. (2023) Faecalibacterium prausnitzii, Bacteroides faecis and Roseburia intestinalis Attenuate Clinical Symptoms of Experimental Colitis by Regulating Treg/th17 Cell Balance and Intestinal Barrier Integrity. Biomedicine & Pharmacotherapy, 167, Article 115568. https://doi.org/10.1016/j.biopha.2023.115568 |
| [37] | Zhao, K., Qiu, L., He, Y., Tao, X., Zhang, Z. and Wei, H. (2023) Alleviation Syndrome of High-Cholesterol-Diet-Induced Hypercholesterolemia in Mice by Intervention with Lactiplantibacillus plantarum WLPL21 via Regulation of Cholesterol Metabolism and Transportation as Well as Gut Microbiota. Nutrients, 15, Article 2600. https://doi.org/10.3390/nu15112600 |
| [38] | Zhang, Y., Zheng, T., Ma, D., Shi, P., Zhang, H., Li, J., et al. (2023) Probiotics Bifidobacterium Lactis M8 and Lactobacillus rhamnosus M9 Prevent High Blood Pressure via Modulating the Gut Microbiota Composition and Host Metabolic Products. mSystems, 8, e0033123. https://doi.org/10.1128/msystems.00331-23 |
| [39] | Wang, L., Hu, J., Li, K., Zhao, Y. and Zhu, M. (2024) Advancements in Gene Editing Technologies for Probiotic-Enabled Disease Therapy. iScience, 27, Article 110791. https://doi.org/10.1016/j.isci.2024.110791 |
