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Table 5 Therapeutic approaches for Alzheimer’s disease: focusing on microbiota and gram-negative bacteria-derived molecules

From: Gram-negative bacteria and their lipopolysaccharides in Alzheimer’s disease: pathologic roles and therapeutic implications

Therapeutic methods Treatment or drug Subject or model Target (or antibiotic range) Effects or trial phase References
Antibiotics Doxycycline APP/PS1 mice Gram-positive bacteria
Gram-negative bacteria
Cognitive dysfunction↓
Neuroinflammation↓
[187]
Gentamicin, Vancomycin, Metronidazole, Neomycin, Ampicillin, Kanamycin, Colistin, and Cefaperazone APP/PS1 mice Gram-positive bacteria
Gram-negative bacteria
Aβ deposition↓
Soluble Aβ↓
Neuronal loss↓
Gliosis↓
[188]
Rifampicin AD patients Gram-positive bacteria
Gram-negative bacteria
Phase 2 NCT03856359
Doxycycline
Rifampicin
AD patients Gram-positive bacteria
Gram-negative bacteria
Phase 3 NCT00439166
Doxycycline
Rifampicin
AD patients Gram-positive bacteria
Gram-negative bacteria
Phase 3 NCT00715858
Minocycline AD patients Gram-positive bacteria
Gram-negative bacteria
Phase 2 NCT01463384
Doxycycline
Rifampicin
AD patients Gram-positive bacteria
Gram-negative bacteria
Dysfunctional behavior↓
Cognitive dysfunction↓
[189]
Gingipain inhibitor COR271
COR286
COR388
BALB/c mice Gingipain Aβ deposition↓
TNF-α↓
Neuronal loss↓
[59]
COR388 AD patients Gingipain Phase 2/3 NCT03823404
Probiotics Lactobacillus acidophilus
Bifidobacterium bifidum
Bifidobacterium
longum
Aβ-administered rats Intestinal microbiota Cognitive dysfunction↓
LTP↑
[190]
Bifidobacterium longum
Lactobacillus acidophilus
APP/PS1 mice Intestinal microbiota Cognitive dysfunction↓
Aβ deposition↓
[191]
Lactobacillus plantarum MTCC1325 D-galactose-induced AD albino rats Intestinal microbiota Aβ deposition↓
NFT↓
Cognitive dysfunction↓
Acetylcholine level↑
[192]
Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum AD patients Intestinal microbiota MMSE score↑ [193]
Lactobacillus casei W56, Lactococcus lactis W19, Lactobacillus acidophilus W22, Bifidobacterium lactis W52, Lactobacillus paracasei W20, Lactobacillus plantarum W62, Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus salivarius W24 AD patients Intestinal microbiota Systemic inflammation↓ [194]
Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium longum AD patients Intestinal microbiota MMSE score↑ [195]
Lactobacillus fermentum, Lactobacillus plantarum, Bifidobacterium lactis Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium longum AD patients Intestinal microbiota Cognitive dysfunction- [196]
Intestinal microbiota reconstruction Mediterranean-style diet MCI patients Non-specific bacteria Changes of the microbiota [157]
Mediterranean-style diet MCI patients Non-specific bacteria Changes of the microbiota [197]
Curcumin APP/PS1 mice Non-specific bacteria Cognitive impairment↓
Aβ deposition↓
Changes of the microbiota
[198]
Folate and vitamin B-12 Aβ-administered rats Non-specific bacteria Changes of the microbiota [199]
Ginsenoside Rg1 Tree shrew model of AD Non-specific bacteria Aβ deposition↓
Phosphorylated tau↓
Pro-apoptotic factor↓
Changes of the microbiota
[200]
Streptococcus thermophilus, Bifidobacteria longum, Bifidobacteria breve, Bifidobacteria infantis, Lactobacillus acidophilus, Lactobacillus plantarum,Lactobacillus paracasei, Lactobacillus delbrueckii subsp, Bulgaricus, Lactobacillus brevis 3xTg mice Intestinal microbiota Cognitive impairment↓
Aβ deposition↓
Neuronal loss↓
[201]
NK46 (Bifidobacterium longum) oral administration 5xFAD mice Gram-negative bacteria Pro-inflammatory cytokines↓
LPS↓
Gliosis↓
Neuronal loss↓
Aβ↓
Cognitive dysfunction↓
[23]
Fecal microbiota transplant ADLPAPT mice Microbiota dysbiosis Aβ deposition↓
NFT↓
Neuroinflammation↓
Cognitive dysfunction↓
[202]
Fecal microbiota transplant AD patients Microbiota dysbiosis MMSE score↑ [203]
Fecal microbiota transplant AD patients Microbiota dysbiosis Phase 1 NCT03998423
  1. Ach Acetylcholine, AD Alzheimer’s disease, Amyloid-β, LPS lipopolysaccharides, LTP long-term potentiation, MCI mild cognitive impairment, MMSE mini-mental state examination, NFT neurofibrillary tangles, NF-kB nuclear factor-κB, SADAScog standardized Alzheimer’s disease assessment scale cognitive subscale