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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Systematic Review Article

Effects of Supplementation with Probiotics in Experimental Models of Alzheimer's Disease: A Systematic Review of Animal Experiments

Author(s): Francisca Idalina Neta, Francisco Emílio Simplício de Souza, André Lima Batista, Francisco Irochima Pinheiro, Ricardo Ney Cobucci and Fausto Pierdoná Guzen*

Volume 19, Issue 3, 2022

Published on: 06 April, 2022

Page: [188 - 201] Pages: 14

DOI: 10.2174/1567205019666220318092003

Price: $65

Abstract

Background: Conditions along the brain-gut-microbiota (BGM) axis can significantly contribute to the pathogenesis of Alzheimer's disease (AD). Evidence from animal studies indicates a role of probiotics in regulating mood, cognition, and stress response via the BGM axis. However, the effect of probiotics on AD needs to be better clarified in preclinical and clinical studies.

Methods: We prepared this systematic review according to PRISMA. PubMed, Web of Science, Embase, and Virtual Health Library (VHL) were searched for original articles concerning the effects of probiotics in experimental AD.

Results: Results were presented as a narrative synthesis according to the Synthesis Without Metaanalysis (SWiM) Guideline. Seventeen studies met the inclusion criteria. The results showed significant effects in the experimental models of AD treated with probiotics alone or in mixture due to expressive improvements in cognitive tests.

Conclusion: Furthermore, in most of the included studies, it was possible to observe a reduction in inflammatory processes, an increase in the concentration of peptide hormones, insulin homeostasis in the brain, increased antioxidant enzymes, and a decrease in beta-amyloid deposition and tau hyperphosphorylation. Supplementation of probiotics seems to improve performance in cognitive tests and increase the concentration of substances capable of delaying the neurodegenerative process of AD in experimental models.

Keywords: Alzheimer's disease, probiotics, neurodegeneration, neuroprotection, intestine, experimental model.

[1]
Caputo M, Monastero R, Mariani E, et al. Neuropsychiatric symptoms in 921 elderly subjects with dementia: A comparison between vascular and neurodegenerative types. Acta Psychiatr Scand 2008; 117(6): 455-64.
[http://dx.doi.org/10.1111/j.1600-0447.2008.01175.x] [PMID: 18363771]
[2]
de Paula VJR, Guimarães FM, Diniz BS, Forlenza OV. Neurobiological pathways to Alzheimer’s disease: Amyloid-beta, TAU protein or both? Dement Neuropsychol 2009; 3(3): 188-94.
[http://dx.doi.org/10.1590/S1980-57642009DN30300003] [PMID: 29213627]
[3]
Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP, Prakash S. Microbiome, probiotics and neurodegenerative diseases: Deciphering the gut brain axis. Cell Mol Life Sci 2017; 74(20): 3769-87.
[http://dx.doi.org/10.1007/s00018-017-2550-9] [PMID: 28643167]
[4]
Friedland RP. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration. J Alzheimers Dis 2015; 45(2): 349-62.
[http://dx.doi.org/10.3233/JAD-142841] [PMID: 25589730]
[5]
Jiang C, Li G, Huang P, Liu Z, Zhao B. The gut microbiota and Alzheimer’s disease. J Alzheimers Dis 2017; 58(1): 1-15.
[http://dx.doi.org/10.3233/JAD-161141] [PMID: 28372330]
[6]
Bateman RJ, Xiong C, Benzinger TLS, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012; 367(9): 795-804.
[http://dx.doi.org/10.1056/NEJMoa1202753] [PMID: 22784036]
[7]
Cryan JF, Dinan TG. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 2012; 13(10): 701-12.
[http://dx.doi.org/10.1038/nrn3346] [PMID: 22968153]
[8]
Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer disease: An update. J Cent Nerv Syst Dis 2020; 12: 1179573520907397.
[http://dx.doi.org/10.1177/1179573520907397] [PMID: 32165850]
[9]
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med 2021; 18(3): e1003583.
[http://dx.doi.org/10.1371/journal.pmed.1003583] [PMID: 33780438]
[10]
Sena ES, Currie GL, McCann SK, Macleod MR, Howells DW. Systematic reviews and meta-analysis of preclinical studies: Why perform them and how to appraise them critically. J Cereb Blood Flow Metab 2014; 34(5): 737-42.
[http://dx.doi.org/10.1038/jcbfm.2014.28] [PMID: 24549183]
[11]
Hooijmans CR, Tillema A, Leenaars M, Ritskes-Hoitinga M. Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed. Lab Anim 2010; 44(3): 170-5.
[http://dx.doi.org/10.1258/la.2010.009117] [PMID: 20551243]
[12]
Campbell M, McKenzie JE, Sowden A, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline. BMJ 2020; 368: l6890.
[http://dx.doi.org/10.1136/bmj.l6890] [PMID: 31948937]
[13]
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 2020; 92: 114-34.
[http://dx.doi.org/10.1016/j.neurobiolaging.2020.04.009] [PMID: 32417748]
[14]
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 2020; 76(3): 1083-102.
[http://dx.doi.org/10.3233/JAD-200436] [PMID: 32623399]
[15]
Woo JY, Gu W, Kim KA, Jang SE, Han MJ, Kim DH. Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model. Anaerobe 2014; 27: 22-6.
[http://dx.doi.org/10.1016/j.anaerobe.2014.03.003] [PMID: 24657159]
[16]
Nimgampalle M, Kuna Y. Anti-Alzheimer properties of probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer’s disease induced albino rats. J Clin Diagn Res 2017; 11(8): KC01-5.
[http://dx.doi.org/10.7860/JCDR/2017/26106.10428] [PMID: 28969160]
[17]
Lee HJ, Lee KE, Kim JK, Kim DH. Suppression of gut dysbiosis by Bifidobacterium longum alleviates cognitive decline in 5XFAD transgenic and aged mice. Sci Rep 2019; 9(1): 11814.
[http://dx.doi.org/10.1038/s41598-019-48342-7] [PMID: 31413350]
[18]
Wu Q, Li Q, Zhang X, et al. Treatment with Bifidobacteria can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice. PeerJ 2020; 8: e10262-2.
[http://dx.doi.org/10.7717/peerj.10262] [PMID: 33194428]
[19]
Mohammadi G, Dargahi L, Peymani A, et al. The effects of probiotic formulation pretreatment (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) on a lipopolysaccharide rat model. J Am Coll Nutr 2019; 38(3): 209-17.
[http://dx.doi.org/10.1080/07315724.2018.1487346] [PMID: 30307792]
[20]
Lee H-J, Lim S-M, Kim D-H. Lactobacillus johnsonii CJLJ103 attenuates scopolamine-induced memory impairment in mice by increasing BDNF expression and inhibiting NF-κB activation. J Microbiol Biotechnol 2018; 28(9): 1443-6.
[http://dx.doi.org/10.4014/jmb.1805.05025] [PMID: 30111074]
[21]
Bonfili L, Cecarini V, Berardi S, et al. Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep 2017; 7(1): 2426.
[http://dx.doi.org/10.1038/s41598-017-02587-2] [PMID: 28546539]
[22]
Bonfili L, Cecarini V, Cuccioloni M, et al. SLAB51 probiotic formulation activates sirt1 pathway promoting antioxidant and neuroprotective effects in an AD mouse model. Mol Neurobiol 2018; 55(10): 7987-8000.
[http://dx.doi.org/10.1007/s12035-018-0973-4] [PMID: 29492848]
[23]
Asl ZR, 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 2019; 376: 112183.
[http://dx.doi.org/10.1016/j.bbr.2019.112183] [PMID: 31472194]
[24]
Bonfili L, Cecarini V, Gogoi O, et al. Gut microbiota manipulation through probiotics oral administration restores glucose homeostasis in a mouse model of Alzheimer’s disease. Neurobiol Aging 2020; 87: 35-43.
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.11.004] [PMID: 31813629]
[25]
Kobayashi Y, Sugahara H, Shimada K, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease. Sci Rep 2017; 7(1): 13510.
[http://dx.doi.org/10.1038/s41598-017-13368-2] [PMID: 29044140]
[26]
Azm SAN, Djazayeri A, Safa M, et al. Probiotics improve insulin resistance status in an experimental model of Alzheimer’s disease. Med J Islam Repub Iran 2017; 31(1): 103.
[http://dx.doi.org/10.14196/mjiri.31.103] [PMID: 29951404]
[27]
Athari Nik Azm S, Djazayeri A, Safa M, et al. Lactobacilli and bifidobacteria ameliorate memory and learning deficits and oxidative stress in β-amyloid (1-42) injected rats. Appl Physiol Nutr Metab 2018; 43(7): 718-26.
[http://dx.doi.org/10.1139/apnm-2017-0648] [PMID: 29462572]
[28]
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 2019; 24(3): 265-73.
[http://dx.doi.org/10.3746/pnf.2019.24.3.265] [PMID: 31608251]
[29]
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 2020; 24(4): 220-8.
[http://dx.doi.org/10.29252/ibj.24.4.220] [PMID: 32306720]
[30]
Barrett E, Ross RP, O’Toole PW, Fitzgerald GF, Stanton C. γAminobutyric acid production by culturable bacteria from the human intestine J Appl Microbiol 2012; 113(2): 411-7.
[http://dx.doi.org/10.1111/j.1365-2672.2012.05344.x] [PMID: 22612585]
[31]
Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol 2013; 6(1): 39-51.
[http://dx.doi.org/10.1177/1756283X12459294] [PMID: 23320049]
[32]
Liu X, Cao S, Zhang X. Modulation of gut microbiota-brain axis by probiotics, prebiotics, and diet. J Agric Food Chem 2015; 63(36): 7885-95.
[http://dx.doi.org/10.1021/acs.jafc.5b02404] [PMID: 26306709]
[33]
Choi YJ, Yang HS, Jo JH, et al. Anti-amnesic effect of fermented Ganoderma lucidum water extracts by lactic acid bacteria on scopolamine-induced memory impairment in rats. Prev Nutr Food Sci 2015; 20(2): 126-32.
[http://dx.doi.org/10.3746/pnf.2015.20.2.126] [PMID: 26176000]
[34]
Briguglio M, Dell’Osso B, Panzica G, et al. Dietary neurotransmitters: A narrative review on current knowledge. Nutrients 2018; 10(5): 591.
[http://dx.doi.org/10.3390/nu10050591] [PMID: 29748506]
[35]
Peña F, Gutiérrez-Lerma A, Quiroz-Baez R, Arias C. The role of beta-amyloid protein in synaptic function: Implications for Alzheimer’s disease therapy. Curr Neuropharmacol 2006; 4(2): 149-63.
[http://dx.doi.org/10.2174/157015906776359531] [PMID: 18615129]
[36]
Rohe M, Synowitz M, Glass R, Paul SM, Nykjaer A, Willnow TE. Brain-derived neurotrophic factor reduces amyloidogenic processing through control of SORLA gene expression. J Neurosci 2009; 29(49): 15472-8.
[http://dx.doi.org/10.1523/JNEUROSCI.3960-09.2009] [PMID: 20007471]
[37]
Matrone C, Ciotti MT, Mercanti D, Marolda R, Calissano P. NGF and BDNF signaling control amyloidogenic route and Abeta production in hippocampal neurons. Proc Natl Acad Sci USA 2008; 105(35): 13139-44.
[http://dx.doi.org/10.1073/pnas.0806133105] [PMID: 18728191]
[38]
Jiao SS, Shen LL, Zhu C, et al. Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Transl Psychiatry 2016; 6(10): e907-7.
[http://dx.doi.org/10.1038/tp.2016.186] [PMID: 27701410]
[39]
Jouanne M, Rault S, Voisin-Chiret AS. Tau protein aggregation in Alzheimer’s disease: An attractive target for the development of novel therapeutic agents. Eur J Med Chem 2017; 139: 153-67.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.070] [PMID: 28800454]
[40]
Lin G, Shindel AW, Fandel TM, Bella AJ, Lin CS, Lue TF. Neurotrophic effects of brain-derived neurotrophic factor and vascular endothelial growth factor in major pelvic ganglia of young and aged rats. BJU Int 2010; 105(1): 114-20.
[http://dx.doi.org/10.1111/j.1464-410X.2009.08647.x] [PMID: 19493269]
[41]
Savignac HM, Corona G, Mills H, et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochem Int 2013; 63(8): 756-64.
[http://dx.doi.org/10.1016/j.neuint.2013.10.006] [PMID: 24140431]
[42]
Karl JP, Margolis LM, Madslien EH, et al. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am J Physiol Gastrointest Liver Physiol 2017; 312(6): G559-71.
[http://dx.doi.org/10.1152/ajpgi.00066.2017] [PMID: 28336545]
[43]
Shimizu M, Hashiguchi M, Shiga T, Tamura HO, Mochizuki M. Meta-analysis: Effects of probiotic supplementation on lipid profiles in normal to mildly hypercholesterolemic individuals. PLoS One 2015; 10(10): e0139795.
[http://dx.doi.org/10.1371/journal.pone.0139795] [PMID: 26473340]
[44]
Toth C, Martinez J, Zochodne DW. RAGE, diabetes, and the nervous system. Curr Mol Med 2007; 7(8): 766-76.
[http://dx.doi.org/10.2174/156652407783220705] [PMID: 18331235]
[45]
Akisaki T, Sakurai T, Takata T, et al. Cognitive dysfunction associates with white matter hyperintensities and subcortical atrophy on magnetic resonance imaging of the elderly diabetes mellitus Japanese elderly diabetes intervention trial (J-EDIT). Diabetes Metab Res Rev 2006; 22(5): 376-84.
[http://dx.doi.org/10.1002/dmrr.632] [PMID: 16506272]
[46]
Kroner Z. The relationship between Alzheimer’s disease and diabetes: Type 3 diabetes? Altern Med Rev 2009; 14(4): 373-9.
[PMID: 20030463]
[47]
Calvo-Barreiro L, Eixarch H, Montalban X, Espejo C. Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis. Autoimmun Rev 2018; 17(2): 165-74.
[http://dx.doi.org/10.1016/j.autrev.2017.11.019] [PMID: 29191793]
[48]
Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body 2021 Available from https://www.frontiersin.org/article/10.3389/fimmu.2021.578386
[http://dx.doi.org/10.3389/fimmu.2021.578386]
[49]
Domingues C, Silva OABC, Henriques AG. Impact of cytokines and chemokines on Alzheimer’s disease neuropathological hallmarks. Curr Alzheimer Res 2017; 14(8): 870-82.
[http://dx.doi.org/10.2174/1567205014666170317113606] [PMID: 28317487]
[50]
Dumitrescu L, Popescu-Olaru I, Cozma L, et al. Oxidative stress and the microbiota-gut-brain axis. Oxid Med Cell Longev 2018; 2018: 2406594.
[http://dx.doi.org/10.1155/2018/2406594] [PMID: 30622664]
[51]
Wang X, Mao M, Zhang SS, Wang ZH, Xu SQ, Shen XF. Bolus norepinephrine and phenylephrine for maternal hypotension during elective cesarean section with spinal anesthesia: A randomized, double-blinded study. Chin Med J (Engl) 2020; 133(5): 509-16.
[http://dx.doi.org/10.1097/CM9.0000000000000621] [PMID: 31996543]
[52]
Xu R, Wang Q. Towards understanding brain-gut-microbiome connections in Alzheimer’s disease. BMC Syst Biol 2016; 10(Suppl. 3): 63.
[http://dx.doi.org/10.1186/s12918-016-0307-y]
[53]
Lee BJ, Bak YT. Irritable bowel syndrome, gut microbiota and probiotics. J Neurogastroenterol Motil 2011; 17(3): 252-66.
[http://dx.doi.org/10.5056/jnm.2011.17.3.252] [PMID: 21860817]
[54]
Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr 2004; 44(4): 275-95.
[http://dx.doi.org/10.1080/10408690490468489] [PMID: 15462130]
[55]
Yadav H, Jain S, Sinha PR. Oral administration of dahi containing probiotic Lactobacillus acidophilus and Lactobacillus casei delayed the progression of streptozotocin-induced diabetes in rats. J Dairy Res 2008; 75(2): 189-95.
[http://dx.doi.org/10.1017/S0022029908003129] [PMID: 18474136]
[56]
Lahiri DK, Maloney B. The “LEARn” (Latent Early-life Associated Regulation) model integrates environmental risk factors and the developmental basis of Alzheimer’s disease, and proposes remedial steps. Exp Gerontol 2010; 45(4): 291-6.
[http://dx.doi.org/10.1016/j.exger.2010.01.001] [PMID: 20064601]
[57]
Maloney B, Lahiri DK. Epigenetics of dementia: Understanding the disease as a transformation rather than a state. Lancet Neurol 2016; 15(7): 760-74.
[http://dx.doi.org/10.1016/S1474-4422(16)00065-X] [PMID: 27302240]
[58]
Leblhuber F, Steiner K, Schuetz B, Fuchs D, Gostner MJ. Probiotic supplementation in patients with Alzheimer’s dementia - An explorative intervention study. Curr Alzheimer Res 2018. Available from: http://www.eurekaselect.com/node/164642/article

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