Table 3 Novel certain animal model studies on live biotherapeutic products (LBPs) in gut brain axis related conditions
Gut brain axis related conditions | LBPs | Subjects | Dose | Intervention duration | Results | Reference |
|---|---|---|---|---|---|---|
Alzheimer Disease | Lactiplantibacillus plantarum | Eight-week-old C57BL/6 J mice (male, n = 60) transgenic (APP/PS1) Five group 1.WT = wild type 2.APP/PS1 mice 3.Memantine group 4. Lactiplantibacillus plantarum group 5.Memantine + Lactiplantibacillus plantarum group | 1 × 109 CFU/mL | 12 weeks | Between APP/PS1 mice group and Lactiplantibacillus plantarum group; Neuroinflammation in the hippocampus was reduced (hippocampus IL-2, IL-17, TNF-α) Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) levels were reduced and hepatic flavin monooxygenase (FMO) activity was increased while FMO3 levels remained constant in the liver The number of Αβ plaques in the hippocampus were decreased | [72] |
Alzheimer Disease | Lactobacillus acidophilus (1688FL431-16LA02), Limosilactobacillus fermentum (ME3), Bifidobacterium lactis (1195SL609-16BS01), Bifidobacterium longum (1152SL593-16BL03) | Sixty male Wistar rats (weight 180–220 g, 8 weeks of age) 1. Control 2. CP: probiotics; S: sham; 3. Aβ: Alzheimer; 4.AP: Alzheimer-probiotics | 2 g (1 × 1010 CFU/g) | 8 weeks | Improved spatial memory Spending more time in the in the target quadrant No significant difference found superoxide dismutase (SOD), catalase (CAT) levels with probiotic supplementation The AP group had significantly much lower levels of malondialdehyde (MDA) than the the Aβ group Between Aβ and AP groups, total Lactobacillus and Bifidobacterium count increased The AP group’s escapelatency and travelled distance were significantly decreased in comparison to the the Aβ group | [73] |
Alzheimer Disease | VSL#3 (Lactiplantibacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii sub sp. Bulgaricus, Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, and Streptococcus salivarius substrain, thermophilus) | C57BL/6 wild-type (WT) mice were compared to AppNL−G−F mice 1.WT 2.WT + VSL3 3.AppNL−G−F mice 4. A4.ppNL−G−F mice + VSL3 | 0.32 × 109 CFU bacteria/25 g mice | 8 weeks | Following probiotic treatment AppNL−G−F mice displayed a significant increase in Clostridia, Lachnospiracea and Akkermansia genera The serum levels acetate, butyrate, lactate, isobutyrate and propionate were increased after probiotic supplementation Acetate and lactate concentrations in the hippocampus region were found to be elevated c-Fos immunoreactivity was increased after probiotic supplementation After probiotic treatment, Aβ, GFAP, and Iba-1 immunoreactivity didn’t affected The levels of Aβ in the hippocampus were unaffected by probiotic treatment Anxiety-like behavior was altered after Probiotic supplementation | [74] |
Alzheimer Disease | Lactiplantibacillus plantarum Bifidobacterium bifidum | Forty male Wistar rats, weight of 280 ± 20 g 1.Control (healthy rats), 2. Receiving Aβ AD models (Aβ), 3. AD rats with MIIT (Aβ + MIIT), 4.AD rats fed Lactiplantibacillus plantarum and Bifidobacterium bifidum (Aβ + PROB), 5. Receiving both treatments for AD rats (Aβ + MIIT + PROB) | 1 × 109 CFU of each strain | 8 weeks | No significant difference BDNF and choline acetyltransferase (CHaT) levels between Aβ and Aβ + PROB groups | [75] |
Alzheimer Disease | Lactobacillus acidophilus, Bifidobacterium bifidum Bifidobacterium longum | Male Sprague–Dawley rats weighing 220∼250 g 1.Sham 2.Alzheimer 3.Alzheimer + Probiotic | 500 mg probiotics [15 × 109 colony-forming units (CFU) | 6 weeks | Decreased escape latency significantly No significant difference in nitric oxide concentration The total cholesterol, triglyceride, and very low-density lipoprotein-cholesterol (VLDL-C) concentrations in the serum and paired-pulse facilitation (PPF) ratio were reduced Increase in field excitatory postsynaptic potentials (fEPSP) | [76] |
Alzheimer Disease | Bifidobacterium. bifidum BGN4 Bifidobacterium. longum BORI | C57BI/6 and 5xFAD mice 1.Control-BGN4/BORI group (n = 10), 2.Control + BGN4/BORI group (n = 10) 3.5xFAD-BGN4/BORI group (n = 10), and 4.5xFAD + BGN4/BORI group (n = 10) | 1 × 109 CFU in 0.2 ml sterile water | 30 days | BDNF protein expression in the hippocampus was increased Amyloid-β42 positive cells were reduced in the hippocampus In cleaved caspase-3 positive cells were decreased Reduced neuronal death in CA3 and CA1 areas of the hippocampus The number of Map2 + /BDNF + neurons in the hippocampus were significantly increased AD-associated memory deficits were improved The expression of IL-17 and IL-6 was reduced | [77] |
Alzheimer Disease | Akkermansia muciniphila GP01 | APPswe/PS1dE9 (APP/PS1) double-transgenic mice WT mice were divided into two groups (n: 6 per group) while APP/PS1 mice were randomly divided into four groups (n: 10 per group) | 5 × 109 CFU of Akkermansia muciniphila in 200 µL sterile PBS | 6 months | Aβ plaque deposits and Aβ levels were reduced in brains Impaired cognition and anxiety-related behaviors were improved Glucose homeostasis was regulated, and damage to the intestinal barrier was reduced Decrease in serum cholesterol and triglyceride levels Uncoupling protein 1 (UCP1) level was increased in brown adipose tissue | [78] |
Alzheimer Disease | Bifidobacterium breve (Bifidobacterium breve NMG, Bifidobacterium breve MY, Bifidobacterium breve CCFM1025, Bifidobacterium breve XY, and Bifidobacterium breve WX) | Eighty 8-week-old, C57BL/6 J male mice Sixty-four mice 1.Control 2.Model-Aβ1-42 3.Donepezil- Aβ1-42 4.Aβ1-42 Bifidobacterium breve NMG 5.Aβ1-42 Bifidobacterium breve MY, 6.Aβ1-42 Bifidobacterium breve CCFM1025, 7.Aβ1-42 Bifidobacterium breve XY 8.Aβ1-42 Bifidobacterium breve WX | 109 CFU/ml for oral administration | 6 weeks | The treatment of Bifidobacterium breve NMG and CCFM1025 resulted in significant improvements in alternation behaviour as well as an increases in total arm entries Bifidobacterium breve treatment improves Aβ1-42-induced memory defects, CCFM1025, XY, and WX significantly reduced Aβ1-42-induced hippocampal accumulation in Aβ1-42 treated mice CCFM1025 treatment significantly improved synaptic plasticity and led to increased concentrations of BDNF, fibronectin type III domain containing 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Interestingly, all bifidobacteria strains raised BDNF concentrations of except MY Butyrate and acetate concentrations were found to be significantly decreased in AD mice, while propionate concentrations were significantly increased The concentration of acetate was significantly increased by 1025 and WX Butyrate concentrations in the feces of the CCFM1025-treated group were significantly increased | [79] |
Parkinson Disease | Clostridium butyricum | C57BL/6 male mice (18–22 g, 6–8 weeks) Three groups: 1.Control group (n: 10) 2. MPTP group (n: 10) 3.MPTP + Cb group (n: 10) | 5 × 108 CFU/0.2 mL/day/mice | 4 weeks | Improved gut microbiota dysbiosis Colonic glucagon-like peptide-1 (GLP-1) levels vere raised Upregulated the expression of cerebral GLP-1 receptor The level of TH in SN was increased. In mice, Cb prevented dopaminergic neuronal loss caused by MPTP In the MPTP group, Cb supplementation could significantly prevent the decreased synapsin I level The effects of Cb treatment on MPTP-induced motor deficits in mice were shown to be effective | [80] |
Parkinson Disease | Lactobacillus acidophilus, Bifidobacterium bifidum, Limosilactobacillus reuteri, and Limosilactobacillus fermentum | Male Wistar rats (weighing 200–250 g) 1.Probiotic group 2.Parkinson group 3.Sham group | Each bacteria 2 × 109 | 14 days | MDA levels in the midbrain decreased as a result of probiotics The number of damaged neurons in the PD group was significantly lower The increase in contralateral rotations was greatly reduced by the application of a probiotic When compared to PD rats, probiotic treatment led to a decrease in escape latency Probiotics significantly prevented the memory impairment as evindenced by an increase the time spent in the target quadrant | [81] |
Parkinson Disease | Ligilactobacillus salivarius AP-32 | Male Sprague–Dawley rats (eight-weeks-old, weight 290 ± 10 g) 1.ND (non-diseased, n: 5) 2.PD (untreated PD, n: 5), 3.LD (PD treated with 8 mg of L-DOPA, n: 5) 4. 1X (PD supplemented with 1.03 × 109 CFU/kg BW of probiotic, n:5), 5.MR (PD supplemented with 62 mg/kg BW of MR, n: 5), 6.1XMR (PD supplemented with a combination of 1X and MR, n:5) | 0.3 × 109 CFU to 0.6 × 109 CFU for 300–600 g BW of rat 1.03 × 109 CFU/kg BW | 8 weeks | Between PD and 1X groups Increased serum SOD, glutathione peroxidase (GPx) and catalase levels, decreased ROS and TNF-α levels Increased total SCFAs, propionic and butyric leves in feces Probiotic supplementation also changed the composition of the fecal microbiota, enriching commersals while reducing some pathogenic bacreria Reduced dopaminergic neuron loss, improved endurance performance, elevated tyrosine hydroxylase (TH +) in the striatum and substantia nigra, and provided neuroprotective effects | [82] |
Parkinson Disease | Lactiplantibacillus plantarum CRL 2130, Streptococcus. thermophilus CRL 808, Streptococcus thermophilus CRL 807 | Eight-week-old C57BL/6 male mice (20–30 g) 1. Control 2. MIX (probiotic) 3. MPTP 4. MPTP/MIX | 8 ± 2 × 108 CFU/mL | 22 days | When comparing the MPTP/mixture group to MPTP group, the number of tyrosine hydroxylase positive cells in the brain increased significantly MPTP-induced LAB-reduced motor deficits When compared to the MPTP group, serum TNF-α, IL-6 levels decreased and IL-10 increased significantly in the MPTP/mixture group When compared to the MPTP group, brain IL-10 increased significantly in the MPTP/mixture group | [83] |
Parkinson Disease | Lactiplantibacillus plantarum PS128 (PS128) | Male Sprague–Dawley rats (10-week-old, ~ 400 g) 1. Saline 2. PS128 3. Levodopa 4. DBS (deep brain stimulation) 5. PS128 + Levodopa 6. PS128 + DBS 7. Levodopa + DBS | 1.5 × 1010 CFU | 6 weeks | PS128-treated rats showed a significant neuroprotective effect; there were 22,3% and 9,9% of TH + areas in the striatum and midbrain, respectively PS128 consumption inhibited the mortality of dopaminergic cell death PS128-Treated improved motor functions in hemi-parkinsonian rats PS128 administration increased brain dopamine availability in hemiparkinsonian rats | [84] |
Parkinson Disease | Bifidobacterium breve strain A1 [MCC1274] (B. breve A1) | Male C57BL/6 mice (7–8 weeks old) 1. Control-Saline, n: 36; 2. Control-Bifidobacterium breveA1, n: 32; 3. Control-Non-viable Bifidobacterium breveA1, n: 5; 4. MPTP-Saline, n: 36; 5. MPTP- Bifidobacterium breveA1, n: 32; 6. MPTP-Non-viable Bifidobacterium breveA1, n: 5 | 1 × 109 CFU | 4 days | In Parkinson disease mice, Bifidobacterium breve A1 restored decreased dendritic Spine Density No significant differences calcium-binding adapter molecule 1 (Iba1) and BDNF, neuropsin mRNA expression decreased Neuropsin mRNA expression decreased, while there was no significant alterations calcium-binding adapter molecule 1 (Iba1) and BDNF | [85] |
Parkinson Disease | Lacticaseibacillus rhamnosus HA-114 | Thirty-one experimentally naive adult male Sprague Dawley rats 1.Sham + Probiotics (n:12) 2.PD + Placebo (n: 9) 3. PD + Probiotics (n: 10) | 108 CFU | 6 weeks | In 6-OHDA-Lesioned Rats, Probiotics treatment wasn’t impact anxiety behaviour There is no difference in the number of dopamine neurons in the two groups Probiotics alleviate hippocampal-dependent cognitive impairments in 6-OHDA lesioned rats | [86] |