Unlocking the Potential of the Gut-Brain Axis for Alzheimer's Disease Treatment through Probiotic Interventions: A Systematic Review

Main Article Content

Yada Siripaopradit
Oranut Chatsirisakul
Tassanee Ariyapaisalkul

Abstract

Introduction


Alzheimer’s disease is a common neurodegenerative disorder in the aging population leading to cognitive and memory impairment. Probiotics, living microorganisms that can promote health benefits when taken appropriately, have been claimed to be potential treatment alternatives for Alzheimer’s disease amidst limited treatment options thus far. This study aimed to review the current evidence on the effects of probiotics on Alzheimer’s disease in animal studies and to point to future directions for further research.


 


Method 


The method utilized in this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Three reviewers searched for the articles on various databases such as PubMed, Scopus, and ScienceDirect. Articles published between 2010 and 2023 were included in the review using the keywords [Gut-brain axis], [Alzheimer], and [Probiotics]. 


 


Results


Several animal studies related to the impact of probiotics on gut microbiota, cognitive function, as well as pathological and metabolic markers  in Alzheimer's disease were systematically reviewed. The result demonstrated an improvement in cognitive function after the probiotic treatment through the regulation of gut microbiota and Aβ deposits and inflammation suppression. In Alzheimer’s disease models in mice, Bifidobacterium breve HNXY26M4 and Lactobacillus plantarum DP189 lead to a decrease in cognitive deficits and neuroinflammation through the gut-brain axis in APP/PS1 (p<0.05) and PI3K/Akt/GSK-3β signaling pathway (p<0.05) respectively.


 


Conclusion 


Probiotics could have the potential to be safe and effective therapies for Alzheimer's disease by adjusting the gut-brain axis and decreasing pathogenic indicators. However, future studies are required to investigate optimal dosages and regimens for clinical uses.

Article Details

How to Cite
Siripaopradit, Y., Chatsirisakul, O. and Ariyapaisalkul, T. (2023) “Unlocking the Potential of the Gut-Brain Axis for Alzheimer’s Disease Treatment through Probiotic Interventions: A Systematic Review”, Journal of Asian Medical Students’ Association. Kuala Lumpur, Malaysia. Available at: https://jamsa.amsa-international.org/index.php/main/article/view/603 (Accessed: 21May2024).
Section
Scientific Papers (AMSC 2023 Taiwan)

References

Guilherme MDS, Nguyen VTT, Reinhardt C, Endres K. Impact of gut microbiome manipulation in 5xFAD mice on Alzheimer’s disease-like pathology. Microorganisms [Internet]. 2021;9(4):815. Available from: http://dx.doi.org/10.3390/microorganisms9040815

Cao J, Amakye WK, Qi C, Liu X, Ma J, Ren J. Bifidobacterium Lactis Probio-M8 regulates gut microbiota to alleviate Alzheimer’s disease in the APP/PS1 mouse model. Eur J Nutr [Internet]. 2021;60(7):3757–69. Available from: http://dx.doi.org/10.1007/s00394-021-02543-x

Athari Nik Azm S, Djazayeri A, Safa M, Azami K, Ahmadvand B, Sabbaghziarani F, et al. Lactobacilli and bifidobacteria ameliorate memory and learning deficits and oxidative stress in β-amyloid (1–42) injected rats. Appl Physiol Nutr Metab [Internet]. 2018;43(7):718–26. Available from: http://dx.doi.org/10.1139/apnm-2017-0648

Wang Q-J, Shen Y-E, Wang X, Fu S, Zhang X, Zhang Y-N, et al. Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice. Aging (Albany NY) [Internet]. 2020;12(1):628–49. Available from: http://dx.doi.org/10.18632/aging.102645

Wang F, Xu T, Zhang Y, Zheng T, He Y, He F, et al. Long-term combined administration of Bifidobacterium bifidum TMC3115 and Lactobacillus plantarum 45 alleviates spatial memory impairment and gut dysbiosis in APP/PS1 mice. FEMS Microbiol Lett [Internet]. 2020;367(7). Available from: http://dx.doi.org/10.1093/femsle/fnaa048

Kobayashi Y, Sugahara H, Shimada K, Mitsuyama E, Kuhara T, Yasuoka A, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease. Sci Rep [Internet]. 2017;7(1):13510. Available from: http://dx.doi.org/10.1038/s41598-017-13368-2

Wu Q, Li Q, Zhang X, Ntim M, Wu X, Li M, et al. Treatment with Bifidobacteria can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice. PeerJ [Internet]. 2020;8(e10262):e10262. Available from: http://dx.doi.org/10.7717/peerj.10262

Lee H-J, Lee K-E, Kim J-K, Kim D-H. Suppression of gut dysbiosis by Bifidobacterium longum alleviates cognitive decline in 5XFAD transgenic and aged mice. Sci Rep [Internet]. 2019;9(1):11814. Available from: http://dx.doi.org/10.1038/s41598-019-48342-7

Cecarini V, Bonfili L, Gogoi O, Lawrence S, Venanzi FM, Azevedo V, et al. Neuroprotective effects of p62(SQSTM1)-engineered lactic acid bacteria in Alzheimer’s disease: a pre-clinical study. Aging (Albany NY) [Internet]. 2020;12(16):15995–6020. Available from: http://dx.doi.org/10.18632/aging.103900

Nimgampalle M, Kuna Y. Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer’s Disease induced Albino Rats. J Clin Diagn Res [Internet]. 2017;11(8):KC01–5. Available from: http://dx.doi.org/10.7860/JCDR/2017/26106.10428

Kaur H, Golovko S, Golovko MY, Singh S, Darland DC, Combs CK. Effects of probiotic supplementation on short chain fatty acids in the AppNL-G-F mouse model of Alzheimer’s disease. J Alzheimers Dis [Internet]. 2020;76(3):1083–102. Available from: http://dx.doi.org/10.3233/JAD-200436

Kaur H, Nagamoto-Combs K, Golovko S, Golovko MY, Klug MG, Combs CK. Probiotics ameliorate intestinal pathophysiology in a mouse model of Alzheimer’s disease. Neurobiol Aging [Internet]. 2020;92:114–34. Available from: http://dx.doi.org/10.1016/j.neurobiolaging.2020.04.009

Ji H-F, Shen L. Probiotics as potential therapeutic options for Alzheimer’s disease. Appl Microbiol Biotechnol [Internet]. 2021;105(20):7721–30. Available from: http://dx.doi.org/10.1007/s00253-021-11607-1

Rezaei Asl Z, Sepehri G, Salami M. Probiotic treatment improves the impaired spatial cognitive performance and restores synaptic plasticity in an animal model of Alzheimer’s disease. Behav Brain Res [Internet]. 2019;376(112183):112183. Available from: http://dx.doi.org/10.1016/j.bbr.2019.112183

Bonfili L, Cecarini V, Cuccioloni M, Angeletti M, Berardi S, Scarpona S, et al. SLAB51 probiotic formulation activates SIRT1 pathway promoting antioxidant and neuroprotective effects in an AD mouse model. Mol Neurobiol [Internet]. 2018;55(10):7987–8000. Available from: http://dx.doi.org/10.1007/s12035-018-0973-4

Rezaeiasl Z, Salami M, Sepehri G. The effects of probiotic Lactobacillus and Bifidobacterium strains on memory and learning behavior, long-term potentiation (LTP), and some biochemical parameters in β-amyloid-induced rat’s model of Alzheimer’s disease. Prev Nutr Food Sci [Internet]. 2019;24(3):265–73. Available from: http://dx.doi.org/10.3746/pnf.2019.24.3.265

Mehrabadi S, Sadr SS. Assessment of probiotics mixture on memory function, inflammation markers, and oxidative stress in an Alzheimer’s disease model of rats. Iran Biomed J [Internet]. 2020;24(4):220–8. Available from: http://dx.doi.org/10.29252/ibj.24.4.220

Bonfili L, Cecarini V, Gogoi O, Berardi S, Scarpona S, Angeletti M, et al. Gut microbiota manipulation through probiotics oral administration restores glucose homeostasis in a mouse model of Alzheimer’s disease. Neurobiol Aging [Internet]. 2020;87:35–43. Available from: http://dx.doi.org/10.1016/j.neurobiolaging.2019.11.004

Patel C, Pande S, Acharya S. Potentiation of anti-Alzheimer activity of curcumin by probiotic Lactobacillus rhamnosus UBLR-58 against scopolamine-induced memory impairment in mice. Naunyn Schmiedebergs Arch Pharmacol [Internet]. 2020;393(10):1955–62. Available from: http://dx.doi.org/10.1007/s00210-020-01904-3

Shamsipour S, Sharifi G, Taghian F. Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer’s disease. Neurosci Lett [Internet]. 2021;756(135949):135949. Available from: http://dx.doi.org/10.1016/j.neulet.2021.135949

Abraham D, Feher J, Scuderi GL, Szabo D, Dobolyi A, Cservenak M, et al. Exercise and probiotics attenuate the development of Alzheimer’s disease in transgenic mice: Role of microbiome. Exp Gerontol [Internet]. 2019;115:122–31. Available from: http://dx.doi.org/10.1016/j.exger.2018.12.005

Téglás T, Ábrahám D, Jókai M, Kondo S, Mohammadi R, Fehér J, et al. Exercise combined with a probiotics treatment alters the microbiome, but moderately affects signalling pathways in the liver of male APP/PS1 transgenic mice. Biogerontology [Internet]. 2020;21(6):807–15. Available from: http://dx.doi.org/10.1007/s10522-020-09895-7

Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasuti C, et al. Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep [Internet]. 2017;7(1):2426. Available from: http://dx.doi.org/10.1038/s41598-017-02587-2

Abdelhamid M, Zhou C, Jung C-G, Michikawa M. Probiotic Bifidobacterium breve MCC1274 mitigates Alzheimer’s disease-related pathologies in wild-type mice. Nutrients [Internet]. 2022;14(12):2543. Available from: http://dx.doi.org/10.3390/nu14122543

Prasad KN. A micronutrient mixture with collagen peptides, probiotics, cannabidiol, and diet may reduce aging, and development and progression of age-related alzheimer’s disease, and improve its treatment. Mech Ageing Dev [Internet]. 2023;210(111757):111757. Available from: http://dx.doi.org/10.1016/j.mad.2022.111757

Webberley TS, Masetti G, Bevan RJ, Kerry-Smith J, Jack AA, Michael DR, et al. The impact of probiotic supplementation on cognitive, pathological and metabolic markers in a transgenic mouse model of Alzheimer’s disease. Front Neurosci [Internet]. 2022;16:843105. Available from: http://dx.doi.org/10.3389/fnins.2022.843105

Webberley TS, Bevan RJ, Kerry-Smith J, Dally J, Michael DR, Thomas S, et al. Assessment of Lab4P probiotic effects on cognition in 3xTg-AD Alzheimer’s disease model mice and the SH-SY5Y neuronal cell line. Int J Mol Sci [Internet]. 2023;24(5). Available from: http://dx.doi.org/10.3390/ijms24054683

Wu Y, Niu X, Li P, Tong T, Wang Q, Zhang M, et al. Lactobacillaceae improve cognitive dysfunction via regulating gut microbiota and suppressing Aβ deposits and neuroinflammation in APP/PS1 mice. Arch Microbiol [Internet]. 2023;205(4):118. Available from: http://dx.doi.org/10.1007/s00203-023-03466-3

Abdelhamid M, Zhou C, Ohno K, Kuhara T, Taslima F, Abdullah M, et al. Probiotic Bifidobacterium breve prevents memory impairment through the reduction of both amyloid-β production and microglia activation in APP knock-in mouse. J Alzheimers Dis [Internet]. 2022;85(4):1555–71. Available from: http://dx.doi.org/10.3233/JAD-215025

Zhu G, Zhao J, Wang G, Chen W. Bifidobacterium breve HNXY26M4 attenuates cognitive deficits and neuroinflammation by regulating the gut-brain axis in APP/PS1 mice. J Agric Food Chem [Internet]. 2023;71(11):4646–55. Available from: http://dx.doi.org/10.1021/acs.jafc.3c00652

Ye T, Yuan S, Kong Y, Yang H, Wei H, Zhang Y, et al. Effect of probiotic fungi against cognitive impairment in mice via regulation of the fungal Microbiota-gut-brain axis. J Agric Food Chem [Internet]. 2022;70(29):9026–38. Available from: http://dx.doi.org/10.1021/acs.jafc.2c03142

Song X, Zhao Z, Zhao Y, Wang Z, Wang C, Yang G, et al. Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl3 induced mouse model of Alzheimer’s disease via modulating gut microbiota and PI3K/Akt/GSK-3β signaling pathway. Nutr Neurosci [Internet]. 2022;25(12):2588–600. Available from: http://dx.doi.org/10.1080/1028415X.2021.1991556

El Sayed NS, Kandil EA, Ghoneum MH. Probiotics Fermentation Technology, a novel Kefir product, ameliorates cognitive impairment in streptozotocin-induced sporadic Alzheimer’s disease in mice. Oxid Med Cell Longev [Internet]. 2021;2021:5525306. Available from: http://dx.doi.org/10.1155/2021/5525306