Table 3.

Summary of animal intervention studies investigating the effects of probiotic formulations on dementia-related outcomes

First author, journal, year (ref)	Animal model	Exposure	Duration	Dementia-related outcomes measured	Main results
Davari, Neuroscience, 201369	Rats with streptozocin-induced diabetes	Probiotic blend with Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus fermentum vs placebo	2 months	Spatial learning tasks (Morris water maze test) Basic and potentiated EPSPs in the CA1 area of hippocampus	Improvement in spatial learning tasks Maintenance of basic and potentiated EPSPs (decline observed in controls)
Distrutti, PLoS One, 201470	Young and aged male Wistar rats	VSL#3 probiotic blend vs maple syrup (control)	6 weeks	EPSPs in dentate gyrus after long-term potentiation shock test Expression of cortical tissue genes detected by microarray analysis	Improvement of cortical expression of genes involved in inflammation modulation and neural plasticity (BDNF, synapsin among others) Attenuation of the age-related deficit in EPSPs after long- term potentiation shock test
Liu, Biomed Res Int, 201571	Mice with vascular dementia induced by a permanent unilateral right common carotid artery occlusion	Clostridium butyricum	6 weeks	Spatial learning tasks (Morris water maze test) Histological signs of neuronal apoptosis in hippocampal tissue BDNF-P13K/Akt pathway protein expression	Improvement in spatial learning tasks Reduced signs of hippocampal neuron apoptosis Activation of BDNF-P13K/Akt pathway-related proteins
Liang, Neuroscience, 201572	Sprague Dawley rats subjected to restraint stress	Lactobacillus helveticus NS8	3 weeks	Anxiety behaviors and memory tasks Plasma cortisol, ACTH and cytokine levels BDNF mRNA expression in prefrontal cortex and hippocampus Brain monoamine neurotransmitters	Reduction of anxiety behaviors and memory dysfunction induced by stress Lower plasma cortisol and ACTH levels, higher IL-10 levels Higher hippocampal BDNF expression
Sun, Brain Res, 201673	Mice with streptozocin-induced diabetes subjected to 30 minutes of bilateral common carotid artery occlusion	C. butyricum	6 weeks	Spatial learning tasks (Morris water maze test) Hippocampal neuron damage and apoptosis Brain expression of Akt, phospho-Akt, caspase-3	Attenuation of decline in spatial learning tasks Attenuation of hippocampal neuron apoptosis Increased expression of Akt, phosphor-Akt and caspase-3, limiting apoptosis in hippocampal neurons
Bonfili, Sci Rep, 201774	3xTg-AD transgenic mice with early-stage Alzheimer’s disease	SLAB51 probiotic	4 months	Multiple tests of	Reduced decline in
		blend containing nine strains (bifidobacteria, lactobacilli and Streptococcus thermophilus)		locomotor activity, recognition memory, fear-motivated reactions, anxiety-related behaviors Amyloid brain deposition Proteasome activity in brain homogenates	performance at cognitive and anxiety-related tests Reduced amyloid accumulation Increased expression of neuronal proteolytic pathways
Nimgampalle, J Clin Diagn Res, 201775	Albino rats with D-galactose induced Alzheimer’s disease	Lactobacillus plantarum	2 months	Spatial learning tasks (Morris water maze test) Gross behavioral activity Brain neuron degeneration Brain acetylcholine level	Improved spatial learning tasks and gross behavior activity Reduced neuron degeneration Maintenance of acetylcholine levels
Kobayashi, Sci Rep, 201776	ddY mice with Aβ injection-induced Alzheimer’s disease	Bifidobacterium breve strain A1	6 days	Alternation behavior in Y maze test Latency time in passive avoidance test Hippocampal neuron gene expression	Prevention of decline in cognitive dysfunction measured with alternation behavior and passive avoidance test Reversal of Aβ-induced change in hippocampal gene expression (reduced expression of proinflammatory genes)
Musa, J Dairy Res, 201777	ICR mice with neuroinflammation induced by lipopolysaccharide brain injection	Lactic acid bacteria probiotic blend derived from fresh cow milk	28 days	Spatial learning tasks (Morris water maze test) Acetylcholine, antioxidant and proinflammatory cytokine levels in brain lysate	Attenuation of neuroinflammation-induced decline in spatial learning tasks Increase of acetylcholine and antioxidant brain levels, reduction of proinflammatory cytokines
Chunchai, J Neuroinflammation, 201878	Male Wistar rats fed with high-fat diet- induced dementia	Lactobacillus paracasei	12 weeks	Spatial learning tasks (Morris water maze test) Microglial activation Brain mitochondrial function Hippocampal plasticity, oxidative stress, apoptosis	Improvement of high-fat diet- induced impairment in spatial learning tasks Reduced microglial activation Improved brain mitochondrial dysfunction Restored hippocampal plasticity and reduced oxidative stress and apoptosis
Athari Nik Azm, Appl Physiol Nutr Metab, 201879	Mice with Aβ injection-induced Alzheimer’s disease	Probiotic blend with L. acidophilus, L. fermentum, B. lactis, Bifodobacterium longum	8 weeks	Spatial learning tasks (Morris water maze test) Hippocampal oxidative stress biomarkers	Reduced decline in spatial learning tasks Improvement in oxidative stress biomarkers (malondialdehyde, superoxide dismutase)

Abbreviations: ACTH, adrenocorticotropic hormone; BDNF, brain-derived neurotrophic factor; EPSP, excitatory postsynaptic potential; IL-10, interleukin-10.