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Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia

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Abstract

Purpose

Probiotics, as live microorganisms that improve intestinal microbial balance, have been implicated in the modulation of neurodegenerative diseases via the microbiome–gut–brain axis by improving gut dysbiosis. This review examines the association between probiotics and neurocognitive function in age-related dementia.

Methods

We searched MEDLINE, Embase, Scopus, Web of Science and Cochrane library for in vivo studies using equivalent combinations of “probiotics” and “dementia” as per PRISMA. From the 52 in vivo studies identified, 5 human and 22 animal studies with comparable quantitative outcomes on neurocognitive/behavioural function were meta-analysed by forest plots, subgroup analysis and meta-regression. The analysis of biomarkers, risk of bias and publication bias were also performed.

Results

In elderly humans, probiotics correlates with a non-significant difference of neurocognitive function in Mini-Mental State Examination, but with significant improvement only in those diagnosed with Alzheimer’s disease. In animals, probiotics significantly improved neurocognitive function as measured by Morris Water Maze, Y-Maze, and Passive Avoidance. Further analysis by subgrouping and meta-regression found that the probiotics-neurodegeneration association is age dependent in humans but is neither dose dependent nor duration dependent in animals or humans. Analysis of biomarkers suggested that the neurocognitive effect of probiotics is associated with an altered gut microbiome profile, downregulated proteinopathic, inflammatory and autophagic pathways, and upregulated anti-oxidative, neurotrophic, and cholinergic pathways.

Conclusion

Overall, we report promising results in animal studies but limited evidence of probiotics leading to neurocognitive improvement in humans. More research into probiotics should be conducted, especially on live biotherapeutic products for targeted treatment of gut dysbiosis and age-related dementia.

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Funding

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Author notes

  1. Henry Yue Hong Meng and Christopher Chi Hang Mak: joint authorship.

Authors and Affiliations

  1. Faculty of Medicine, The Chinese University of Hong Kong, Central Ave, Hong Kong, People’s Republic of China

    Henry Yue Hong Meng

  2. School of Clinical Medicine, University of Cambridge, Hills Road, Cambridge, CB20QQ, UK

    Christopher Chi Hang Mak

  3. Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China

    Wing Yan Mak & Francis Ka Leung Chan

  4. Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, China

    Tao Zuo

  5. Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China

    Ho Ko

Authors
  1. Henry Yue Hong Meng
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  2. Christopher Chi Hang Mak
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  3. Wing Yan Mak
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  4. Tao Zuo
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  5. Ho Ko
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  6. Francis Ka Leung Chan
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Contributions

Prof. Francis Ka Leung Chan is the guarantor of this review article. HYH and CHC have joint authorship of this publication. HYH, CHC and WYM performed the literature review and wrote the manuscript. HYH and CHC drafted the tables and figures. WYM and FKL proposed the review project, WYM, TZ, HK and FKL critically revised the manuscript, WYM and FKL supervised the review process. All authors approved the final version of the article, including the authorship list.

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Correspondence to Henry Yue Hong Meng.

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Documentation

The progress of this study has been documented from conception on ResearchGate (https://www.researchgate.net/project/Probiotic-modulation-on-neurocognitive-decline).

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Meng, H.Y.H., Mak, C.C.H., Mak, W.Y. et al. Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia. Eur J Nutr 61, 1701–1734 (2022). https://doi.org/10.1007/s00394-021-02760-4

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  • DOI: https://doi.org/10.1007/s00394-021-02760-4

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