TABLE 1.
Summarizing documented effects of Pre, Pro, and Synbiotic formulations on AD patients and animal models of AD.
| Probiotics | Subject/Model | Effect | Source |
| Lactobacillus johnsonii | GF mice | Decreased serum levels of kynurenine (a by-product of tryptophan) and increased serotonin levels by 140%. Suggesting that the probiotic promoted the serotonergic pathway over the neurotoxic kynurenine pathway | Valladares et al., 2013 |
| Bifidobacterium infantis | Sprague-Dawley rats | Plasma concentration of tryptophan increased whereas the concentration of kynurenic acid decreased, followed by a decrease in the pro-inflammatory response from the kynurenine pathway | Desbonnet et al., 2008 |
| Lactobacillus fermentum NCIMB 5221 | Male APPswe and PS1ΔE9 mutant transgenic mice | Produces Ferulic acid, a natural antioxidant and anti-inflammatory agent. Pretreatment of FA to Aβ induced mice resulted in the mitigation of neuroinflammation Aβ fibril formation, and restored memory deficits | Westfall et al., 2017; Mori et al., 2019 |
| SLAB51 (Streptococcus thermophilus, Bifidobacterium longum, B. breve, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus, L. brevis) | 3 × Tg-AD-mice | Restoration of SIRT1 protein deacetylase activity. Stimulation of the ADAM-10 α-secretase, cleaving APP in a non-amyloidogenic pathway, inhibiting the formation of Aβ. Decreased acetylation of p53 protein, promoting neuronal cell survival | Bonfili et al., 2018 |
| Lactobacillus plantarum MTCC1325 | D-galactose induced AD-mice | Restored overall ATPase enzyme levels for all subjects in the cerebral cortex (CC) and hippocampus (HP) regions. Recovered Na+ and K+ ATPases in the CC and HP, leading to the regulation of membrane ionic gradient for an adequate neuronal activity | Nimgampalle and Yellamma, 2017; Chiroma et al., 2018 |
| Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum | Human AD patients | MMSE score increasd relative to the AD patients, significant decrease in CRP levels and a decelerated rate at which insulin resistance affects the brain and subseqquent neuronal cell death | Akbari et al., 2016 |
| Lactobacillus plantarum WCFS1, E. coli Nissle and Bifidobacterium infantis spp. | – | Proficient in producing SCFAs such as butyrate, propionate and acetate. The former also has BA metabolism properties; a mechanism important in reducing the amount of cytotoxic secondary BAs in the brain | Kowalski and Mulak, 2019 |
| Bifidobacterium bifidum Bb | Human normal subjects | Increase in Ruminococcaceae and a decrease in Prevotellaceae, further increasing fecal butyrate levels, a helpful SCFA involved in the reduction of neuroinflammation | Gargari et al., 2016 |
| Fructo-oligosaccharides (FOS) | Male APPswe and PS1ΔE9 mutant transgenic mice | Increase in GLP-1 when compared to AD-mice, promoting satiety and slowing gastric emptying and forestalling CNS insulin resistance, thus decelerating neuronal cell death. Also, FOS lead to an increase in synapsin-1 when compared to the diminished expression of the protein in AD mice, resulting in normal neuronal activity | Sun et al., 2018 |
| Xylo-oligosaccharides (XOS) | APP/PS1 mice | Significantly increased levels of Muribacterium and Lactobacillus in POCD mice, genera that were deficient in POCD-APP/PS Mice. Attenuated levels of the pro-inflammatory cytokines IL-6, of IL-1β, and the immunosuppressive cytokine IL-10. Also increased ZO-1 levels in epithelium and hypothalamus tissue countering the leaky gut and leaky brain phenotype of AD-mice. Restored TREM2 levels, leading to the normalization of microglia neuroinflammatory response. Induces growth of Bifidobacterium adolescentis and Bifidobacterium longum, the former being documented for its neuroinflammatory properties | Ávila et al., 2020; Han et al., 2020 |
| Polyphenols (Ferulic Acid) | Female APPswe and PS1ΔE9 mutant transgenic mice | Acts as a ROS scavenger, diminishing neurotoxicity. Inhibits formation of Aβ fibrils at the cortical and hippocampal level. Decrease in IL-1β pro-inflammatory cytokine | Yan et al., 2001 |
| Triphala (TFLA) | – | Reduces neuronal deterioration, improved longevity, motility, reduced Aβ accumulation, and increased acetylcholinesterase activity | Westfall et al., 2019 |
| Synbiotics | |||
| Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum and selenium | UAS-(β-secretase) BACE1-APP AD-induced Drosophila melanogaster | Same effects as mentioned above for triphala, albeit more potent in every category, especially Aβ accumulation and acetylcholinesterase activity | Westfall et al., 2019 |
| Lactobacillus plantarum NCIMB 8826, Lactobacillus fermentum NCIMB 5221 and Bifidobacteria longum spp. infantis NCIMB 702255 and Triphala | Human AD patients | Improvement in MMSE score, reduced hsCRP in plasma, and reduced plasma total antioxidant capacity and glutathione. Markers of insulin metabolism and dyslipidemia were also decreased by the supplementation of the synbiotic | Tamtaji et al., 2018 |
| Kefir | Human Ad patients | Notable improvement in all cognitive tests: memory, visual-spatial, executive function and language due to the decreease in ROS compounds such as O2–, H2O2, ONOO–/OH–, and the increase in ROS scavenging compounds such as NO. Also, synbiotic supplementation lead to a decrease in pro-inflammatory cytokine expression, and an increase in anti:pro-inflammatory ratio | Ton et al., 2020 |
| Lactobacillus paracasei HII01 and XOS | Male Wistar obbese insulin-resistant rats | improved cerebral function by mitigating gut inflammation, hippocampal oxidative stress and microglial activation | Chunchai et al., 2018 |