TABLE 1.

Summary of different psychobiotic treatment results in neurodegenerative and psychiatric diseases

Subjects	Treatment	Outcome	Authors, year
Alzheimer's disease
3 × Tg‐AD† mice	Lactobacillus plantarum PS128	↓ Gliosis Regulated the propionic acid levels Regulated glycogen synthase kinase 3 beta activity	Huang et al., 2021 47
15–17 months old Lister Hooded rats	Lactobacillus acidophilus CUL60, Lactobacillus acidophilus CUL21, Bifidobacterium bifidum CUL20, and Bifidobacterium lactis CUL34	↑ GABA ↑ Glutamine ↑ BDNF† ↓ Microglial activation Restored synaptic plasticity ↑ Task‐specific memory ↑ Spatial learning and memory	O'Hagan et al., 2017 48
Aβ†‐injected ddY mice	Bifidobacterium breve A1	↓ Aβ‐induced gene expression ↑ Plasma acetate level ↑ Spatial memory Prevented Aβ†‐induced cognitive dysfunction	Kobayashi et al., 2017 49
D‐galactose‐injected Wistar rats	Lactobacillus plantarum MTCC1325	↓ AchE† ↑ Ach† in the cortex and hippocampus ↓ Amyloid plaques in the cortex and hippocampus ↑ Spatial memory	Nimgapalle and Kuna, 2017 50
3 × Tg‐AD† mice	SLAB51 formulation: Streptococcus thermophilus, Bifidobacterium. longum, Bifidobacterium breve, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus. paracasei, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus brevis	↑ Ghrelin ↑ Leptin ↑ GIP† ↓ Aβ† deposits ↓ Cathepsin B ↑ Cathepsin L	Bonfilli et al., 2017 51
Aβ†‐injected Wistar rats	Lactobacillus acidophilus, Lactobacillus fermentum, Bifidobacterium lactis, and Bifidobacterium longum	↓ Amyloid plaques ↓ Inflammation ↓ MD†A† and SOD† ↑ Spatial memory Changed fecal microbiota composition	Athari et al., 2018 52
5XFAD Tg mice	Lactobacillus plantarum C29	↓ Amyloid plaques ↓ Caspase 3 expression ↓ NF‐κB activation ↑ BDNF† ↑ Microglial activation	Lee et al., 2021 53
AD† patients	Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum	↑ MMSE† score ↓ MDA† ↓ CRP† ↓ Triglyceride	Akbari et al., 2016 54
AD† patients	Lactobacillus fermentum, Lactobacillus plantarum, Bifidobacterium lactis, Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum	↑ TYM† score ↑ GSH† No effect on antioxidant status	Agahi et al., 2018 55
AD† patients	Lactobacillus casei W56, Lactococcus lactis W19, Lactobacillus acidophilus W22, Bifidobacterium lactis W52, Lactobacillus paracasei W20, Lactobacillus plantarum W62, Bifidobacterium lactis W51, Bifidobacterium bifidum W23 and Lactobacillus salivarius W24	↑ Kynurenine ↑ Immune cell activation ↓ Fecal zonulin Changed stool microbiota composition	Leblhuber et al., 2018 56
AD† patients	Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium longum, and selenium	↑ MMSE† score ↓ CRP† ↓ Triglyceride ↑ GSH† ↑ TAC†	Tamtaji et al., 2019 57
Parkinson's disease
MitoPark PD† mice	Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, Lactobacillus rhamnosus GG, Lactobacillus plantarum LP28, and Lactococcus lactis subsp. lactis	Improved gait Improved beam balance Improved motor coordination ↓ Dopaminergic neuronal loss Preserved TH†‐positive cells in substantia nigra	Hsieh et al., 2020 58
MPTP†‐induced PD† in C57BL/6 mice	Lactobacillus rhamnosus GG, Bifidobacterium animalis lactis, and Lactobacillus acidophilus	↑ Butyrate production ↑ BDNF† ↓ MAO‐B† in the striatum ↑ Dopamine synthesis Preserved the nigral dopaminergic neurons	Srivastav et al., 2019 59
6‐OHDA†‐induced PD† in C57BL/6 mice	SLAB51 formulation	↑ BDNF† ↑ PPARγ† ↓ Neuronal loss ↑ Antioxidative effects	Castelli et al., 2020 60
MPTP†‐induced PD† in C57BL/6 mice	Lactobacillus plantarum CRL2130, Streptococcus thermophilus CRL807, and Streptococcus thermophilus CRL808	↑ Motor skills ↑ TH†‐positive cells ↑ IL10 ↓ IL6 ↓ TNFα	Perez Visnuk et al., 2020 61
PD† patients	Lactobacillus acidophilus and Bifidobacterium infantis	↓ Abdominal pain ↓ Constipation ↓ Bloating	Georgescu et al., 2016 62
PD† patients	Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Bifidobacterium longum, Bifidobacterium bifidum, and Lactobacillus reuteri	↑ SBM† Improved stool consistency ↓ Constipation	Tan et al., 2021 63
PD† patients	Lactobacillus casei Shirota	Improved stool consistency ↓ Bloating ↓ Abdominal pain ↓ Constipation	Cassani et al., 2011 64
PD† patients	Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum	↓ IL1 ↓ IL8 ↓ TNFα ↑ TNFβ ↑ PPARγ†	Borzabadi et al., 2018 65
PD† patients	Streptococcus salivarius subsp. thermophilus, Enterococcus faecium, Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp bulgaricus, and Bifidobacterium (breve and animalis subsp. lactis	↑ CBM† ↓ Constipation Improved stool consistency	Barichella et al., 2016 66
Depression
Mice exposed to chronic restraint stress	Bifidobacterium adolescentis	↓ IL‐1β ↓ TNF‐α ↓NF‐κB p65 ↓ Iba1 ↑ BDNF† in the hippocampus ↑ Lactobacillus level in feces ↓ Bacteroides level in feces	Guo et al., 2019 67
Corticosterone‐induced depression in mice	Lactobacillus paracasei PS23, live or heat‐killed	Live PS23: ↓ Abnormal behavior ↑ BDNF† in the hippocampus ↑ Serotonin in hippocampus, prefrontal cortex and striatum Heat‐killed PS23: ↓ Abnormal behavior ↑ BDNF† in the hippocampus ↑ Dopamine levels in hippocampus and prefrontal cortex.	Wei et al., 2019 68
Healthy Swiss mice	Lactobacillus plantarum 286	Anti‐depressant‐like effects Anxiolytic‐like effects	Barros‐ Santos et al., 2020 69
Wistar rats exposed to chronic unpredictable mild stress	Lactobacillus rhamnosus JB‐1	↑ GABA ↑ Glutamate ↑ GSH† ↑ N‐acetylaspartate	Kochalska et al., 2020 70
C57BL/6J mice exposed to chronic stress	Bifidobacterium breve CCFM1025	Changed gut microbiota composition ↑ SCFAs† ↑ 5‐Hydroxytryptophan ↑ BDNF†	Tian et al., 2020 71
Corticosterone‐induced depression in Sprague–Dawley rats	Lactobacillus plantarum DP189	Improved memory and spatial learning ↓ Anhedonia ↓ IL‐1β ↓ TNFα ↓ BAX ↑ Bcl‐2	Zhao et al., 2020 72
Lipopolysaccharide‐induced anxiety in adolescent CD1 mice	BGOS†	Anxiolytic effect ↓ IL‐1β ↑ 5‐HT2A receptor expression	Savignac et al., 2016 73
C57BL/6J mice exposed to chronic psychosocial stress	FOS† + GOS†	↑ Cecal acetate and propionate level ↓ Cecal isobutyrate level ↑ BDNF† expression in the hippocampus ↓ L‐tryptophan, ↓ Corticosterone ↓ Proinflammatory cytokines	Burokas et al., 2017 74
Sprague–Dawley rats exposed to chronic unpredictable mild stress	FOS†	↓ Depression‐like behaviors Repaired intestinal epithelia damages Changed fecal microbial composition	Chi et al., 2020 75
C57BL/6J mice exposed to subchronic and mild social defeat stress	Heat‐killed Lactobacillus helveticus strain MCC1848	↑ The interaction time in the social interaction test ↑ Sucrose preference ratio in the sucrose preference test Modulated gene expression in the nucleus accumbens	Maehata et al., 2019 76
Healthy C57BL/6 mice	Heat‐killed Lactobacillus fermentum and Lactobacillus delbrueckii	Sedative behavior effect ↓ Corticosterone level Changed gut microbiota composition	Warda et al., 2019 77
Healthy C57BL/6J mice	Heat‐killed Enterococcus faecalis strain EC‐12	↓ Anxiety‐like behavior ↓ Depressive‐like behavior	Kambe et al., 2020 78
Adults with moderate mood swings	Lactobacillus helveticus R0052 and Bifidobacterium longum R0175	Non‐effective in treating low mood No effects on inflammation	Romijn et al., 2017 79
Moderately stressed adults	Lactobacillus plantarum DR7	↓ Symptoms of stress anxiety ↓ Total psychological scores ↓ Cortisol ↓ IFNγ ↓ TGFα ↑ IL10 Enhanced the serotonin pathway Stabilized the dopamine pathway	Chong et al., 2019 80
Moderately stressed adults	Lactobacillus plantarum P8	↓ Scores of stress ↓ Anxiety ↓ IFNγ ↓ TNFα Enhanced memory and cognitive traits	Lew et al., 2019 81
Healthy adults	Heat‐killed Lactobacillus paracasei MCC1849	Improved resistance to common cold infections Maintained a desirable mood state	Murata et al., 2018 82
Young adult students preparing for the national examination	Heat‐inactivated Lactobacillus gasseri CP2305	↓ Anxiety ↓ Sleep disturbance Changed gut microbiota composition	Nishida et al., 2019 83
Patients with major depressive disorder	Lactobacillus plantarum 299v + SSRI	Improved cognitive performance ↓ Kynurenine	Rudzki et al., 2019 84
Adult patients with moderate depression	Lactobacillus casaei + Lactobacillus acidofilus + Lactobacillus bulgarigus + Lactobacillus rhamnosus + Bifidobacterium breve + Bifidobacterium longum + Streptococcus thermophilus + FOS + fluoxetine	↓ Depressive clinical symptoms	Ghorbani et al., 2018 85
Adult patients with mild‐to‐moderate depression	Lactobacillus helveticus Rosell® − 52 + Bifidobacterium longum Rosell® − 175 + SAMe† + magnesium oxide + vitamin B6	↓ PHQ‐9† and HAM‐D† scores	Ullah et al., 2022 86
Adult patients with major depressive disorder	Freeze‐dried Bifidobacterium breve CCFM1025	↓ Serum serotonin turnover ↓ HDRS‐24† and MADRS† scores	Tian et al., 2022 87
Schizophrenia
Sprague Dawley rats	BGOS† + olanzapine	↓ Olanzapine‐induced weight gain ↑ Cognitive flexibility ↑ Acetate production	Kao et al., 2018 88
C57BL/6 mice on a high‐fat diet	Akkermansia muciniphilasub (Akk I subtype, GP01 strain) + olanzapine	Did not suppress the olanzapine‐induced weight gain ↑ Locomotion ↓ Insulin, total cholesterol, triglycerides ↓ ALT†, AST† ↓ Gluconeogenesis and insulin resistance ↓ IL‐6 and TNFα	Huang et al., 2021 89
Sprague Dawley rats	FOS† + GOS†	↑ NMDA† receptor subunits in the hippocampus ↑ NR2A subunits in hippocampus ↑ NR1 and d‐serine in frontal cortex	Savignac et al., 2013 90
BALB/c mice	Lactobacillus rhamnosus JB‐1	↑ GABA in hippocampus and prefrontal cortex	Janik et al., 2016 91
C57BL/6J mice	FOS† + GOS†	↑ GABA‐B1 receptor gene expression in the hippocampus ↑ GABA‐B2 receptor gene expression in the hippocampus	Burokas et al., 2017 92
Sprague Dawley rats	BGOS†	↑ NMDA† cortical receptor function Improved performance in a set‐shifting task	Gronier et al., 2018 93
SCZ† patients	Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis Bb12	No effects on SCZ† symptoms (PANSS† score) ↑ BDNF† Patients were less likely to develop severe bowel difficulties	Dickerson et al., 2014 94
Patients with SCZ† and schizoaffective disorder	Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis Bb12	No effects on SCZ† symptoms (PANSS† score) ↑ BDNF† ↑ Macrophage inflammatory protein 1β.	Tomasik et al., 2015 95
SCZ† patients	Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis Bb12	No effects on SCZ† symptoms (PANSS† score) but greater effects were seen for positive symptoms rather than negative symptoms Improvement in positive symptoms and bowel movement in Candida albicans seronegative males	Severance et al., 2017 96
Bipolar disorder
BD† patients	Bifidobacterium bifidum, Bifidobacterrium lactis, Bifidobacterium longum, and Lactobacillus acidophilus	↓ Mania ↓ Depression	Shahrbabaki et al., 2020 97
BD† patients	Lactobacillus casei W56, Lactobacillus acidophilus W22, Lactobacillus paracasei W20, Bifidobacterium lactis W51, Lactobacillus salivarius W24, Lactococcus lactis W19, Bifidobacterium lactis W52, Lactobacillus plantarum W62, Bifidobacterium bifidum W23	↑ Attention ↑ Psychomotor processing speed ↓ Mania	Reininghaus et al., 2020 98

Abbreviations: AD, Alzheimer's disease; AchE, acetylcholine esterase; Ach, acetylcholine; ALT, alanine‐transaminase; AST, aspartate‐transaminase; Aβ, amyloid beta; BD, bipolar disorder; BDNF, brain‐derived neurotrophic factor; B‐GOS, Bimuno™ galacto‐oligosaccharide; CBM, complete bowel movements; CRP, C‐reactive peptide; FOS, fructo‐oligosaccharides; GIP, gastric inhibitory polypeptide; GOS, galacto‐oligosaccharides; GSH, glutathione; HAM‐D, Hamilton Depression Rating Scale; HDRS‐24, Hamilton Depression Rating scale‐24 Items; MADRS, Montgomery‐Asberg Depression Rating Scale; MAO‐B, monoamine oxidase B; MDA‐ malondialdehyde; MMSE, Mini‐Mental State Examination; MPTP, 1‐methyl‐4‐phenyl‐1,2,3,6,‐tetrahydropyridine; NMDA, N‐methyl–D‐aspartate; PANSS, Positive and Negative Syndrome Scale; PD, Parkinson's disease; PHQ‐9, Patient Health Questionnaire‐9; PPARγ, peroxisome proliferator‐activated receptor gamma; SAMe, S‐adenosyl‐L‐methionine disulfate p‐toluenesulfonate; SBM, spontaneous bowel movements; SCFAs, short‐chain fatty acids; ^†SCZ, schizophrenia; SOD, superoxide‐dismutase; TAC, total antioxidant capacity; TH, tyrosine hydroxylase; TYM, Test Your Memory; 6‐OHDA, 6‐hydroxydopamine.