Efficacy and safety of probiotics in treatment of patients with mild cognitive impairment and Alzheimer's disease

doi:10.3760/cma.j.issn.1007-1245.2024.01.001

Abstract

Abstract:

Objective　To explore the efficacy and safety of probiotics in the treatment of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods　The PubMed, Cochrane Library, EMbase, China National Knowledge Infrastructure, Database for Chinese Technical Periodicals, WanFang Data, and China Biology Medicine disc were searched to collect the studies on the efficacy and safety of probiotics in the treatment of patients with MCI and AD from their establishment to November, 2022. Two reviewers independently screened the literatures, extracted the data, and assessed the risk of bias of the included studies. Meta-analysis was performed using the RevMan 5.4.1 software. Results　A total of 10 studies involving 716 patients were included. The results of the meta-analysis showed that the Mini-Mental State Examination score of the probiotic group was better than that of the control group (MD=1.23, 95%CI 0.18-2.27, P=0.02). There was no statistical difference in the incidence of adverse reactions between the two groups (OR=0.63, 95%CI 0.25-1.63, P=0.34). Conclusion　Probiotics have positive effectiveness in improving the cognitive function of patients with MCI and AD, with satisfactory safety.

Key words:

Alzheimer's disease, Probiotics, Mild cognitive impairment, Meta-analysis

摘要：

目的　探讨益生菌增补治疗轻度认知障碍（MCI）和阿尔茨海默病（AD）患者的有效性及安全性。方法　检索PubMed、Cochrane Library、Web of Science、Embase、中国生物医学文献数据库、知网、维普及万方数据库，搜集所有关于益生菌增补治疗AD及MCI患者有效性及安全性的研究，时间从建库至2022年12月。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用RevMan 5.3软件进行meta分析。结果　共纳入10个研究，716例患者。meta分析结果显示：益生菌组在提高简易智力状态检查量表（MMSE）积分（MD=1.23，95%CI 0.18～2.27，P=0.02）方面优于对照组，差异有统计学意义；两组不良反应发生率差异无统计学意义（OR=0.63，95%CI 0.25～1.63，P=0.34）。结论　益生菌增补治疗在改善MCI和AD患者认知功能效果方面具有积极作用，且具有良好的安全性。

关键词:

阿尔茨海默病, 益生菌, 轻度认知障碍, meta分析

Wu Yanjiao, Chen Liping, Hou Huaijing, Xu Ziqing, Zhang Lingyun.

Efficacy and safety of probiotics in treatment of patients with mild cognitive impairment and Alzheimer's disease [J]. International Medicine and Health Guidance News, 2024, 30(1): 1-7.

武琰娇陈丽萍侯怀晶徐紫清张凌云.

益生菌治疗轻度认知障碍和阿尔茨海默病患者的有效性及安全性 [J]. 国际医药卫生导报, 2024, 30(1): 1-7.

References

[1] Chowdhary N, Barbui C, Anstey KJ, et al. Reducing the risk of cognitive decline and dementia: WHO recommendations [J]. Front Neurol, 2022, 12:765584. DOI: 10.3389/fneur.2021.765584.
[2] DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer's disease [J]. Mol Neurodegener, 2019, 14(1): 32. DOI: 10.1186/s13024-019-0333-5.
[3] Szabo A , Rainavolgyi E. The brain-immune-gut triangle: innate immunity its it psychiatric and neurological disorders [J]. Curr Immunol Rev, 2013, 9(4): 248. DOI: 10.2174/1573395509666131203225659.
[4] Bailey MT, Dowd SE, Galley JD, et al. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation [J]. Brain Behav Immun, 2011, 25(3): 397-407. DOI: 10.1016/j.bbi.2010.10.023.
[5] Sudo N. Biogenic amines: signals between commensal microbiota and gut physiology [J]. Front Endocrinol (Lausanne), 2019, 10: 504. DOI: 10.3389/fendo. 2019.00504.
[6] van de Wouw M, Boehme M, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations [J]. J Physiol, 2018, 596(20):4923-4944. DOI: 10.1113/JP276431.
[7] Kobayashi Y, Sugahara H, Shimada K, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer's disease [J]. Sci Rep, 2017, 7(1): 13510. DOI: 10.1038/s41598-017-13368-2.
[8] Collins SM, Bercik P. Gut microbiota: intestinal bacteria influence brain activity in healthy humans [J]. Nat Rev Gastroenterol Hepatol, 2013, 10(6):326-327. DOI: 10.1038/nrgastro.2013.76.
[9] Zhu G, Zhao J, Zhang H, et al. Probiotics for mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis [J]. Foods, 2021, 10(7): 1672. DOI: 10.3390/foods10071672.
[10] Liu N, Yang D, Sun J, Li Y. Probiotic supplements are effective in people with cognitive impairment: a meta-analysis of randomized controlled trials [J]. Nutr Rev, 2023, 81(9): 1091-1104. DOI: 10.1093/nutrit/nuac113.
[11] 王晶,江秀丽,雷小晶,等. 益生菌制剂联合盐酸多奈哌齐治疗轻、中度阿尔茨海默病的研究[J]. 神经损伤与功能重建,2022,17(7):378-383. DOI:10.16780/j.cnki.sjssgncj. 20220143.
[12] 刘义. 益生菌与盐酸多奈哌齐联合治疗对阿尔茨海默症认知功能及肠道菌群的影响[D].遵义: 遵义医科大学,2021.
[13] 王晓东,李先强. 四磨汤联合肠道微生态制剂对阿尔茨海默病患者认知功能的影响[J]. 河南中医, 2015, 35(8): 1810-1812. DOI:10.16367/j.issn.1003-5028.2015. 08.0762.
[14] 贺继平,苏晓云,李文青,等. 联合应用益生菌对阿尔兹海默症患者肠道菌群及认知功能的影响[J]. 黑龙江医药,2022,35(3):595-598. DOI:10.14035/j.cnki.hljyy.2022.03.037.
[15] Tamtaji OR, Heidari-Soureshjani R, Mirhosseini N, et al. Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: a randomized, double-blind, controlled trial [J]. Clin Nutr, 2019, 38(6): 2569-2575. DOI: 10.1016/j.clnu.2018.11.034.
[16] Kobayashi Y, Kuhara T, Oki M, et al. Effects of Bifidobacterium breve A1 on the cognitive function of older adults with memory complaints: a randomised, double-blind, placebo-controlled trial [J]. Benef Microbes, 2019, 10(5): 511-520. DOI: 10.3920/BM2018.0170.
[17] Akbari E, Asemi Z, Daneshvar Kakhaki R, et al. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trial [J]. Front Aging Neurosci, 2016, 8: 256. DOI: 10.3389/fnagi.2016.00256.
[18] Asaoka D, Xiao J, Takeda T, et al. Effect of probiotic bifidobacterium breve in improving cognitive function and preventing brain atrophy in older patients with suspected mild cognitive impairment: results of a 24-week randomized, double-blind, placebo-controlled trial [J]. J Alzheimers Dis, 2022, 88(1):75-95. DOI: 10.3233/JAD-220148.
[19] 朱满连. 酪酸梭菌活菌胶囊在轻中度阿尔茨海默病中的应用[J]. 中国医师杂志,2021,23(2):291-293. DOI:10.3760/cma.j.cn431274-20191226-01465.
[20] 马莉,赵敏强,范思海,等. 肠道益生菌联合加兰他敏片对阿尔茨海默病患者认知功能及治疗安全性的影响研究[J]. 中国药物与临床,2021,21(14):2427-2429. DOI:10.11655/zgywylc2021.14.002.
[21] Kesika P, Suganthy N, Sivamaruthi BS, et al. Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease [J]. Life Sci, 2021, 264: 118627. DOI: 10.1016/j.lfs.2020.118627.
[22] Bahar-Fuchs A, Clare L, Woods B. Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer's disease and vascular dementia [J]. Cochrane Database Syst Rev, 2013(6): CD003260. DOI: 10.1002/14651858.CD003260.pub2.
[23] Ascone L, Garcia Forlim C, Gallinat J, et al. Effects of a multi-strain probiotic on hippocampal structure and function, cognition, and emotional well-being in healthy individuals: a double-blind randomised-controlled trial [J]. Psychol Med, 2022:1-11. DOI: 10.1017/S0033291722000988.
[24] Hu J, Amor DR, Barbier M, et al. Emergent phases of ecological diversity and dynamics mapped in microcosms [J]. Science, 2022, 378(6615): 85-89. DOI: 10.1126/science.abm7841.
[25] Li B, He Y, Ma J, et al. Mild cognitive impairment has similar alterations as Alzheimer's disease in gut microbiota [J]. Alzheimers Dement, 2019, 15(10):1357-1366. DOI: 10.1016/j.jalz.2019.07.002.
[26] Liu P, Wu L, Peng G, et al. Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort [J]. Brain Behav Immun, 2019, 80: 633-643. DOI: 10.1016/j.bbi.2019.05.008.
[27] Guarner F, Khan AG, Garisch J, et al. World Gastroenterology Organisation Global Guidelines: probiotics and prebiotics October 2011 [J]. J Clin Gastroenterol, 2012, 46(6): 468-481. DOI: 10.1097/MCG.0b013e3182549092.