Table 1. Summary of studies assessing the response to probiotic administration for treating brain and psychologic disorders.

Neurological disorder	Subjects	Probiotic treatment formula	Treatment duration	Treatment effects	Level of evidence for dysbiosis treatment*	References
Alzheimer’s disease (AD)	79 patients with AD, age range between 55–100 years. Patients were randomly assigned to receive either probiotic plus selenium (200 μg/day), only selenium (200 μg/day) or placebo.	Lactobacillus (L.) acidophilus, Bifidobacterium (B.) bifidum, and B. longum	12 weeks	Probiotic with selenium co-supplementation improved cognitive function and regulates metabolic abnormality and oxidative stress.	Level II	Tamtaji et al. (2019) 79
	48 people with AD (age range between 65–90 years old) were divided into control group ( n  = 23) and probiotic group ( n  = 25).	L. fermentum , L. plantarum , B. lactis , L. acidophilus , B. bifidum , and B. longum	12 weeks	Observed regulation of serum metabolites, however, authors concluded that cognitive and biochemical parameters are insensitive to the probiotic supplementation. Moreover, probiotic formulation and dosage, the severity of AD and time of administration deeply affects results treatment.	Level III	Agahi et al. (2018) 76
Parkinson’s disease (PD)	120 patients with PD were randomly assigned (2:1) to either a fermented milk containing multiple probiotic strains plus prebiotic fiber ( n  = 80, aged 71.8 ± 7.7), or placebo ( n  = 40, aged 69.5 ± 10.3).	Streptococcus (S.) salivarius subsp thermophilus , Enterococcus (E.) faecium , L. rhamnosus GG , L. acidophilus, L. plantarum , L. paracasei , L. delbrueckii subsp bulgaricus , and B. (breve and animalis subsp lactis). Prebiotic treatment: Fructooligosaccharides	4 weeks	In the treatment group, there was a significant increase in the number of complete bowel movements, improvements in bowel frequency, stool consistency, and frequency of laxative usage. Therefore, probiotic supplementation improved constipation in PD patients.	Level II	Barichella et al. (2016) 55
Multiple sclerosis (MS)	65 patients with MS (18–50 years old) were randomized into intervention ( n  = 32) and received 2 multi-strain probiotic capsules daily, or into control group ( n  = 33).	Bacillus subtilis PXN 21 , B. bifidum PXN 23 , B. breve PXN 25 , B. infantis PXN 27 , B. longum PXN 30 , L. acidophilus PXN 35 , L. delbrueckii ssp. bulgaricus PXN 39 , L. casei PXN 37 , L. plantarum PXN 47 , L. rhamnosus PXN 54 , L. helveticus PXN 45 , L. salivarius PXN 57 , L. lactis ssp. lactis PXN 63 , S. thermophilus PXN 66, plus cellulose and vegetable capsule ( Hydroxypropylmethyl cellulose ).	6 months	Probiotic supplementation for six months resulted in greater improvement in mental health parameters of patients with MS, significantly reducing depression severity, improving depression symptoms and life quality, reducing fatigue, and improving inflammatory biomarkers.	Level II	Rahimlou et al. (2022) 78
	60 MS patients (18–55 years old) were randomly allocated into probiotic ( n  = 30) or placebo ( n  = 30) group.	L. acidophilus, L. casei, B. bifidum, and L. fermentum	12 weeks	Probiotic supplementation showed favorable effects on the scores of Expanded Disability Status Scale (EDSS), improved mental health parameters, inflammatory markers, insulin resistance, HDL-, total-/HDL-cholesterol and malondialdehyde levels.	Level II	Kouchaki et al. (2017) 79
Insomnia	156 adults (19–65 years) with subclinical symptoms of depression, anxiety, and insomnia were randomly assigned to receive either supplement ( n  = 78) or a placebo ( n  = 78).	L. reuteri NK33 and B. adolescentis NK98	8 weeks	Probiotic supplementation improved sleep quality, especially sleep induction.	Level II	Lee et al. (2021) 80
Depression	40 participants (between 20 and 40 years) with self-reported insomnia were randomly assigned into 2 groups, probiotic, or placebo group.	Lactobacillus plantarum PS128	30 days	Daily probiotic supplementation may improve depressive symptoms and sleep quality of insomniacs.	Level II	Ho et al. (2021) 81
	110 patients with major depressive disorder (MDD) (aged 36.5 ± 8.03). Subjects were randomly assigned to receive probiotic ( n  = 38), prebiotic ( n  = 36), or placebo ( n  = 36).	L. helveticus and B. longum. Prebiotic treatment: Galactooligosaccharide	8 weeks	The subjects with MDD that received probiotic supplements showed an improvement in Beck Depression Inventory (BDI) score compared with placebo, while no significant effect of prebiotic supplementation was observed.	Level II	Kazemi et al. (2019) 82
	105 obese participants (18–55 years old), were included in a double-blind, randomized, placebo-controlled trial that included a 12-week weight loss period based on moderate energy restriction, followed by 12 weeks of weight maintenance. During the two phases, subjects received probiotic formulation ( n  = 62) or placebo ( n  = 63).	L. rhamnosus GMCC1.3724 Prebiotic treatment: Oligofructose and inulin	24 weeks	The supplementation significantly increased weight loss and decreased food craving and BDI score when comparing to placebo group, as well as a better score in the Body Esteem Scale questionnaire. In men, the supplementation improved fasting fullness and cognitive restraint.	Level II	Sanchez et al. (2017) 83
Anxiety	120 college students (aged between 18 and 24 years): 60 were allocated into anxiety group and 60 into control group.	B. longum, B. lactis , B. adolescentis , Streptococcus (S.) thermophiles , L. acidophilus , and L. delbrueckii	15 consecutive days (twice per day)	Probiotic supplementation group presented decreased anxiety scores and restored microbiota imbalance to the standard level.	Level II	Qin et al. (2021) 84
Depression and anxiety	423 postnatal women (mean age: 33 years) were allocated into HN001 ( n  = 212, mean age 33.5 ± 4.24) or placebo ( n  = 211, mean age: 33.7 ± 4.44) group.	L. hamnosus HN001	45 weeks	Postnatal women who received the probiotic had significantly lower depression and anxiety scores in the postpartum period. The offered probiotic may be convenient for the prevention or treatment of depression and anxiety postpartum symptoms.	Level II	Slykerman et al. (2017) 85
Autism spectrum disorder (ASD)	30 autistic children (aged 5 to 9 years), and 30 gender- and age-matched healthy controls were recruited.	L. acidophilus, L. rhamnosus , and B. longum	3 months	The probiotic supplementation significantly improved the autism severity and gastrointestinal (GI) symptoms.	Level II	Shaaban et al. (2018) 86
	85 preschoolers with ASD (mean age: 4.2 years) were randomly allocated into probiotics ( n  = 42) or placebo ( n  = 43).	S. thermophilus, B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. para-casei, and L. delbrueckii	6 months	The group treated with probiotics improved some GI symptoms, adaptive functioning, and sensory profiles. Results suggest positive effects of probiotics on core autism symptoms.	Level III	Santocchi E et al. (2020) 87
Schizophrenia	60 patients with chronic schizophrenia (mean age: 44 years) received either co-supplementation of 50,000 IU vitamin D 3 plus probiotic ( n  = 30) or placebo ( n  = 30).	L. acidophilus, B. bifidum, L. reuteri and L. fermentum plus 50,000 IU of vitamin D3	12 weeks	The probiotic significantly improved general and total Positive and Negative Syndrome Scale (PANSS) scores and, metabolic profiles.	Level II	Ghaderi et al. (2019) 88
	65 patients with schizophrenia were assigned to probiotic group ( n  = 33, mean age: 44.8 ± 11.2) or placebo group ( n  = 32, mean age: 48.1 ± 9.4).	L. rhamnosus strain GG and B.animalis subsp. lactis strain Bb12	14 weeks	The authors suggest that supplementation with probiotics might ameliorate GI leakage in schizophrenia patients.	Level II	Tomasik et al. (2015) 89
Bipolar disorder (BD)	20 euthymic individuals with BD. All participants received the probiotic supplementation for 3 months	L. casei W56, L acidophilus W22, L. paracasei W20, B. Lactis W51 and W52, L. salivarius W24, B. bifidum W23, L. plantarum W26, Lactococcus lactis W19.	3 months	The probiotic supplementation may improve the cognitive function, which might lead to better psychosocial, occupational, work, and financial functioning, in BD patients.	Level IV	Reininghaus et al. (2018) 90

Notes: *This level of evidence rating scheme is based on the following: Ackley BJ, Swan BA, Ladwig G, Tucker S. (2008). Evidence-based nursing care guidelines: Medical-surgical interventions. (p. 7). St. Louis, MO: Mosby Elsevier.