Review Volume 12, Issue 4 pp 4010—4039

Efficacy of probiotics on cognition, and biomarkers of inflammation and oxidative stress in adults with Alzheimer’s disease or mild cognitive impairment — a meta-analysis of randomized controlled trials

Haoyue Den1, , Xunhu Dong2, , Mingliang Chen2,3, , Zhongmin Zou2, ,

  • 1 State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing 400042, China
  • 2 Department of Chemical Defense, School of Military Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
  • 3 Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China

Received: July 25, 2019       Accepted: January 24, 2020       Published: February 15, 2020
How to Cite

Copyright © 2020 Den et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Probiotics are live microbes that confer health benefits to the host. Preliminary animal evidence supports the potential role of probiotics in ameliorating cognitive health, however, findings from clinical trials in Alzheimer’s disease (AD) or mild cognitive impairment (MCI) subjects are controversial. Thus, a meta-analysis is needed to clarify the efficacy of probiotics on cognition in AD or MCI patients. EMBASE, PubMed, Web of Science and Cochrane library were systematically searched and manually screened for relevant published randomized controlled trials (RCTs). Among the 890 citations identified, 5 studies involving 297 subjects met eligibility. There was a significant improvement in cognition (SMD = 0.37; 95% CI, 0.14, 0.61; P = 0.002; I2 = 24%), while a significant reduction in malondialdehyde (SMD = −0.60; 95% CI, −0.91, −0.28; P = 0.000; I2 = 0.0%) and high-sensitivity C-reactive protein (SMD = −0.57; 95% CI, −0.95, −0.20; P = 0.003; I2 = 0.0%) post-intervention levels between the probiotics and control group. This meta-analysis indicated that probiotics improved cognitive performance in AD or MCI patients, possibly through decreasing levels of inflammatory and oxidative biomarkers. However, current evidence is insufficient, and more reliable evidence from large-scale, long-period, RCT is needed.


AD: Alzheimer’s disease; MCI: mild cognitive impairment; GM: gut microbiota; MGB: microbiota-gut-brain axis; CNS: central nervous system; CENTRAL: Cochrane Central Register of Controlled Trials; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCTs: randomized controlled trials; SMD: standardized mean difference; CIs: confidence intervals; SD: standard deviation; SEM: standard error of the mean; MMSE: Mini-Mental State Examination; TYM: Test Your Memory; VLT: verbal learning test; ACPT: auditory continuous performance test; DST: digit span test; NINCDS-ADRDA: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (ADRDA); RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; DSM-5: Diagnostic and Statistical Manual of Mental Disorders, 5th edition; MDA: malondialdehyde; hs-CRP: high-sensitivity C-reactive protein; TAC: total anti-oxidant capacity; GSH: total glutathione; NO: nitric oxide; ROS: reactive oxygen species; BBB: blood-brain barrier.