Table 1.

The influence of probiotic interventions on various neurological disorders and mood disorders.

Probiotic Strain	Study Model	Age	No. of Subjects	Dose and Duration	Results	Ref.
Cognition
Probiotic sticks (B. longum 1714)	Healthy volunteers	25.5 mean years	22	The probiotic stick contained maltodextrin, magnesium stearate and 1 × 109 CFU of probiotics per stick; 1 stick per day for 4 weeks	Improved cognitive performance. Improved visuospatial memory performance and anti-stress, precognitive effects	[17]
Ecologic® Barrier (B. bifidum W23, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W16, and L. lactis W58).	Healthy female volunteers	18 to 40 years	61	5 × 109 CFU per day for 4 weeks.	Improved cognitive response and working memory performance	[112]
B. breve A1	Patients with MCI	-	27	2.0 × 1010 CFU per day for 24 weeks	Improved cognitive function	[113]
B. breve A1	Older adults with memory complaints	50 to 80 years	121	2.0 × 1010 CFU per day for 12 weeks	Improved cognitive function	[114]
B. bifidum, B. infantis, L. helveticus, fructooligosaccharides and maltodextrin.	C57BL/6J mice	21 days *	-	Bifidobacterium (1.9  ×  108 CFU/g); Lactobacillus (6.4  ×  109 CFU/g) were administered with drinking water to female mice from embryonic day 0.5 to postnatal day 21.	Decreased the incidence of ASD Prevented a series of MIA-induced ASD-relevant deficits. Reduced impairments in social behaviour, repetitive behaviour, stereotyped behaviour, depression, and anxiety-like behaviour. Prevented the decrease in PV+ neurons and GABA levels	[117]
ProtexinR restore (L. casei, L. rhamnosus, S. thermophilus, B. breve, L. acidophilus, B. infantis, L. bulgaricus)	Young male golden Syrian hamsters	-	50	2 × 108 CFU/Kg body weight dissolved in PBS; once a day for 27 days	Ameliorated the glutamate excitotoxicity	[118]
L. plantarum C29 mediated fermented soybean (DW2009)	Physically healthy men and women with MCI	55 to 85 years	100	1.25 × 1010 CFU/g per day for 12 weeks	Enhanced cognitive function. Increased BDNF levels Attenuated the memory impairment.	[119]
L. plantarum (LAB1, LAB11, LAB12), L. fermentum (LAB9, LAB10), and L. casei (LABPC)	Male ICR mice and BV2 microglia cell lines	2 months	30	L. fermentum (109 CFU) and L. casei (109 CFU) per day for 28 days	Attenuated the LPS-induced memory deficit. Increased the antioxidants SOD, GSH, and GPx. Reduced the neuroinflammation by decreasing MDA, AChE, and pro-inflammatory cytokines	[121]
Autism spectrum disorder
Delpro® (L. acidophilus, L. casei, L. delbrueckii, B. longum and B. bifidum) with lyophilized peptidoglycan, muramyl peptides and DNA motifs derived from L. rhamnosus V strain	Children with ASD and frequent GI distress	3 to 16 years	33	2 billion CFU of each strain/ thrice a day for 21 days	Improved GI symptoms and autism treatment evaluation domains such as speech, communication, sociability, sensory awareness, physical behaviour, and health	[41]
DSF Vivomixx® (S. thermophilus, B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus)	ASD children	18 to 72 months	85	450 billion/ packet. Two packets/day in the first month; 1 packet/day in the next 5 months	Showed positive effects on core autism symptoms. Significantly improved GI symptoms, multisensory processing, and adaptive functioning.	[42]
VSL#3 (L. delbrueckii subsp. Bulgaricus, L. acidophilus, B. breve, B. longum, B. infantis, L. paracasei, L. plantarum, S. thermophiles)	ASD children	12 years	-	9  ×  1010 CFU/g of B. breve, B. longum, B. infantis; 8  ×  1010 CFU/g of L. acidophilus, L. plantarum, L. paracasei, L. bulgaricus, L. delbrueckii subsp.; 20  × 1010 CFU/g of S. thermophilus and S. salivaricus/ day for 4 weeks	Reduced the severity of abdominal symptoms. Autistic core symptoms improved. The score of the social affect domain improved	[43]
Lactobacillus plantarum WCSF1	ASD children	4 to 16 years	-	4.5 × 1010 CFU per day for 12 weeks	Increased the abundance of Enterococci and Lactobacilli. Decreased the abundance of Clostridium cluster XIVa. Improved stool consistency and behavioural scores	[122]
A mixture of 3 Lactobacillus strains, 2 Bifidobacterium strains, and one Streptococcus strain (60: 25: 15 ratio)	ASD children and their non-autistic siblings and other healthy children as control	ASD (2 to 9 years) Siblings (5 to 7 years) Control (2 to 11 years)	ASD (n = 10); Siblings (n = 9); Control (n = 10)	4 months	Probiotic supplementation normalized Bacteroidetes/Firmicutes ratio. Decreased the abundance of Desulfovibrio spp. and decreased TNFα level in feces	[123]
L. plantarum PS128	ASD boys	7 to 15 years	80	3 × 1010 CFU per day for 4 weeks	Ameliorated defiance behaviours. Improved the Swanson, Nolan, Pelham-IV-Taiwan version (SNAP-IV) scores	[124]
Parkinson’s disease
L. acidophilus, B. infantis	PD patients with GI-NMS	76.05 ± 2.09 years	120	3 months	Improved abdominal pain and bloating compared to the drug trimebutine.	[50]
L. casei Shirota	PD patients with chronic constipation	-	40	65 mL of fermented milk containing 6.5 × 109 CFU/ day for 6 weeks.	Improved stool consistency and bowel habits	[51]
Fermented milk with prebiotic fibre (L. rhamnosus GG, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. Bulgaricus, Bifidobacterium, prebiotic fibre)	PD patients with ROME III criteria constipation	Test: 71.8 ± 7.7 years; placebo: 69.5 ± 10.3 years	120	125 mL fermented milk containing 250 × 109 CFU/day for 4 weeks	Improved frequency of bowel movements	[52]
L. salivarius LS01, L. plantarum LP01, L. acidophilus LA02, L. rhamnosus LR06, B. breve BR03, B. animalis subsp. lactis BS01	PBMCs (isolated from PD patients)	70 ± 8 years	-	1 × 106 cells/plate of PBMCs treated with probiotic strains in a 1:1 ratio for 24 h	Decreased the pro-inflammatory cytokines (TNF-α, IL-17A, and IL-6) and oxidative stress levels. Reduced the growth of pathogens such as E. coli, Klebsiella pneumoniae	[53]
L. acidophilus, B. bifidum, L. reuteri, L. fermentum	PD patients	50 to 80 years	50	2 × 109 CFU per strain; 8 × 109 CFU per capsule; one capsule per day for 12 weeks.	Improved expression of IL-1, IL-8, TNF-α, TGF-β, and PPAR-γ. No changes were observed in inflammation and oxidative stress marker	[54]
S. thermophilus DSM 32245, B. lactis DSM 32246, B. lactis DSM 32247, L. acidophilus DSM 32241, L. helviticus DSM 32242, L. paracasei DSN 32243, L. plantarum DSM 32244, L. brevis DSM 27961	Male C57BL/6 mice, SH-SY5Y cell line.	9 weeks	30	One sachet containing 200 billion bacteria dissolved in 10 mL of drinking water. Mice received 270 µL using oral gavage daily for 2 weeks	SLAB51® was able to counteract the detrimental effect of 6-OHDA. Improved anti-inflammatory and antioxidant activities. Protected dopaminergic neurons and improved behavioural impairments.	[55]
The commercial probiotic mixture contained L. rhamnosus GG, B. animalis lactis, L. acidophilus	MPTP-induced male C57BL/6 mice PD model	7 weeks old	-	2 × 106 CFU per day for 30 days	Induced the butyrate synthesis and increased the BDNF and GDNF levels Enhanced the survival and proliferation of dopaminergic neurons. Reduced the expression of monoamine oxidase B expression and increased the expression of neurotrophic factors.	[56]
Hexbio® (L. acidophilus, L. casei, L. lactis, B. infantis, B. longum) ProbioM8 (Bifidobacterium animalis subsp. lactis)	PD patients with ROME III criteria constipation PD patients	50 to 80 years 69.41  ±   6.05 years	48 Probiotic (n = 50) Probiotic + conventional drug (n = 50)	107 mg of each strain (30 × 109 CFU), 2% FOS and lactose/ twice daily for 8 weeks 2G Probio M8 contains 3 × 1010 CFU/day; maltodextrin as an excipient, once daily for 3 months.	Improved bowel opening frequency and whole gut transit time Reduced anxiety and depression. Regulate gut lipid metabolism, SCFAs, and neurotransmitters. Increased dopaminergic synthesis	[125] [58]
Alzheimer’s disease
L. acidophilus, L. casei, L. fermentum, B. bifidum,	AD patients	60 to 95 years	60	200 mL probiotic milk containing 2 × 109 CFU/g of each strain per day for 12 weeks.	Improved MMSE score. Decreased MDA and serum hs-CRP	[65]
L. acidophilus, B. bifidum, B. longum with selenium	AD patients	55 to 100 years	79	200 µg selenium and probiotic containing 2 × 109 CFU of each strain per day for 12 weeks	Improved cognitive function. Reduced serum triglycerides, LDL, total-/HDL cholesterol, hs-CRP	[66]
Iranian Prodigest Capsule composed of L. acidophilus, B. bifidum and B. longum	Aβ injected Male Sprague-Dawley rats.	-	40	15 × 109 in 1 mL drinking water for 4 weeks and given via ICV for 4 weeks	Improved learning. Increased paired-pulse facilitation ratios. Reduced serum triglycerides and very LDL	[69]
L. reuteri, L. rhamnosus, B. infantis	Aβ injected male Wistar rats.	-	50	1 × 1010 CFU per day for 10 weeks	Significantly improved spatial memory Reduced Aβ plaques in AD rats. Reduced inflammatory markers IL-1β and TNF-α, and oxidative stress in AD rats.	[70]
Clostridium butyricum WZMC1016	APPswe/PS1dE9 Tg mice	2 months	20	1 × 109 CFU per day for 4 weeks	Attenuated microglia-mediated neuroinflammation	[72]
L. acidophilus (1688FL431-16LA02), L. fermentum (ME3), B. lactis (1195SL609-16BS01), B. longum (1152SL593-16BL03)	Aβ injected rats	-	60	1 × 1010 CFU each strain per day in drinking water (30 mL) every morning.	Improved memory deficit and inhibited AD pathology by modifying microbiota	[73]
B. breve A1	Aβ injected mice	10 weeks		1× 109 CFU	Improved cognitive function and ameliorated behaviour deficits. Suppressed the immune reactive and inflammation genes in the hippocampus. Significantly enhanced acetate level	[74]
L. plantarum MTCC1325	D-Galactose-induced AD albino rats	-	48	D-Galactose and probiotics 12 × 108 CFU/mL; 10 mL/kg body weight per day for 60 days	Ameliorated cognitive deficits and restored Ach Produced anti-Alzheimer properties against D-Galactose-induced AD rats. Restored spatial memory impairment	[126]
Depression, anxiety and stress
B. longum 1714, and B. breve 1205	Innately anxious BALB/c mice	7 weeks	-	Probiotics reconstituted in PBS; 1 × 109 CFU per day for 6 weeks	Reduced anxiety, stress and depression-related behaviours and weight loss in the anxious mouse Reduced stress-induced hyperthermia	[90]
Fermented milk containing Actimel® (L. delbrueckii subsp. bulgaricus, S. salivarius subsp. thermophilus, L. casei DN114001)	Healthy students under examination stress	18 to 23 years	155	200 mL fermented milk containing 1 × 107/mL CFU L. delbrueckii subsp. bulgaricus, 1 × 108 CFU/mL S. salivarius subsp. thermophilus, and L. casei DN114001 per day for 6 weeks	Significantly increased circulating lymphocytes and CD 56 immune cells	[92]
L. plantarum P-8	Stressed adults	-	Probiotic (n = 43) Placebo (n = 36)	2 × 1010 CFU per day for 12 weeks	Improved the production of neurotransmitters and neuroactive metabolites. Modulates the gut microbes. Reduced stress and anxiolytic effects	[97]
B. longum NCC3001	IBS patients with mild to moderate anxiety and depression scores	-	44	Probiotic sachet containing 1.0 × 1010 CFU/g and maltodextrin dissolved in 100–200 mL lactose-free milk per day for 6 weeks	Decreased HAD scores and depression levels significantly. Reduced responses to negative stimuli	[98]
Probiotic capsule containing L. acidophilus, L. casei and B. longum	Patients with MDD	20 to 55 years	40	2 × 109 CFU per day for 8 weeks	Decreased Beck’s depression scores significantly Significantly raised plasma total glutathione levels	[99]
L. acidophilus Rosell-52, B. longum Rosell-175	Healthy human volunteers with symptoms of stress	18 to 60 years	75	3 × 109 CFU each strain per day for 3 weeks	No significant changes were observed in psychological symptoms and sleep problems. Reduced stress-induced GI symptoms such as abdominal pain, nausea, and vomiting	[127]
A multivitamin capsule containing probiotics L. acidophilus, B. bifidum, B. longum.	Adult men and women suffered from stress and exhaustion.	-	42	1 g capsule containing multivitamins and 10 million strains per day for 6 months	Improved immune health and GI health	[128]
Synbiotics supplement contained L. helveticus R0052, B. longum R0175, L. rhamnosus R0011, galactooligosaccharide and other nutrients.	Healthy stressed individuals	-	32	For 4 weeks	Increased beneficial bacteria load Lactobacillus and Bifidobacterium. Increased the psychological indices significantly for both positive and negative mood states	[129]
Ecologic ® Barrier containing B. bifidum W23, B. lactis W51, W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W19 and L. lactis W58.	Participants with mild to severe depression	18 and above years	71	1 × 1010 CFU per day for 8 weeks	Improved cognitive reactivity. No significant differences were found between groups in the BDI, DASS and BAI scores	[130]

* C57BL/6J mice were administered probiotics during a timed mating procedure, and pups separated on the 21st day after the weaning period. CFU: Colony forming unit; MCI: Mild cognitive impairment; ASD: Autism spectrum disorder; MIA: Maternal immune activation: PV+: parvalbumin positive neurons; GABA: Gamma-aminobutyric acid; PBS: Phosphate buffer saline; BDNF: Brain derived neurotrophic factor: ICR: Institute of cancer research; BV2 microglial cell lines: microglial cell derived from C57/BL6 murine; LPS: Lipo polysaccharide; SOD: Super oxide dismutase; GSH: Glutathione; GP: Glutathione peroxidase; MDA: Malondialdehyde; AchE: Acetylcholine esterase; GI: Gastrointestinal; TNF-α: Tumour necrosis factor α; PD: Parkinson’s disease; GI-NMS: Gastrointestinal Non-motor symptoms; PBMCs: Peripheral blood mononuclear cells; IL-17A: Interleukin 17A; IL6: Interleukin6; IL: 1-Interleukin1; IL-8: Interleukin 8; IL1β: Interleukin 1β; TGF-β: Tumour growth factor-β; PPAR-γ: Peroxisome proliferator-activated receptor gamma; C57BL/6J: C57 Black 6 Jackson laboratory strain mice; SH-SY5Y cells: Thrice sub-cloned cell line from SK-N-SH neuroblastoma cells; 6-OHDA: 6-hydroxydopamine; MPTP: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; GDNF: Glial cell-line derived neurotrophic factor; AD: Alzheimer’s disease; MMSE: Mini-Mental State Examination; hs-CRP- High sensitivity C-reactive protein; LDL: Low density lipoprotein; HDL: High density lipoprotein; ICV: Intracerebroventricular; Aβ: Amyloid beta; APPswe/PS1DE9 Tg: Two transgenes with AD mutation with a chimeric mouse and human amyloid beta precursor protein with Swedish mutation and human presenilin-1 (PS-1) lacking exon 9 (dE9), under the mouse prion protein promoter containing transgenic mice. Ach: Acetylcholine; BALB/c mice: Albino laboratory-bred strain of house mouse; CD56: Cluster of differentiation 56; IBS: Irritable bowel syndrome; HAD: Hospital anxiety depression scale; MDD: Major depressive disorder; BDI: Beck depression index; BAI: Beck anxiety inventory; DASS: Depression anxiety stress scale.