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. 2022 Jul 15;23(14):7820. doi: 10.3390/ijms23147820

Table 3.

A collection of clinical studies on the effects of probiotic supplementation in people diagnosed with selected disease entities.

Type of Examination Study Population Preparation/Probiotic Bacteria Duration of the Intervention Results Statistical Significance References
DEPRESSION Pilot study 12 patients diagnosed with SSRI-treatment-resistant depression (mean age, 19.8 ± 5.7 years) Magnesium orotate (1600 mg), and probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, amd Streptoccocus thermophiles) (total CFU 2 × 1010 divided between 2 daily doses) 16 weeks (active intervention administered for 8 weeks)

  • Reduction in depressive symptoms

  • Improved quality of life after the end of the intervention

  • SSD in 2 scores after 8 weeks of supplementation (both p = 0.005)

  • SID in BDI score in relapse after 16-week follow-up (p = 0.068)

 [53]
Double-blind, placebo controlled, randomized, multi-centre, pilot clinical study 40 patients with mild to moderate IBS and MDD (mean age, 40.36 ± 10.28 years) Bacillus coagulans MTCC 5856 (2 × 109 CFU) (1 tablet per day) 90 days

  • Improvement in IBS and depression symptoms

  • SSD in 3 scores in the treated group (each p ≤ 0.001)

 [55]
Placebo-controlled, double-blind randomized controlled trial 45 patients with mild to moderate IBS and MDD (mean age, 51.32 ± 16.11 years) Bifidobacterium breve CCFM1025 (total CFU 1010) (1 sachet per day) 4 weeks

  • Better antidepressant-like effect

  • Reduced gastrointestinal symptoms

  • SSD in 3 scores in the treated group (each p < 0.001) and in 2 scores in the placebo group (p < 0.001; p = 0.036)

 [56]
Randomized, double-blind, controlled placebo trial 40 patients with a diagnosis of major depressive disorder (age range: 20–55) Lactobacillus acidophilus (2 × 109 CFU/g),
Lactobacillus casei (2 × 109 CFU/g), and
Bifidobacterium bifidum (2 × 109 CFU/g) (1 capsule per day)		 8 weeks

  • Reduction in the Beck Depression Rating Scale

  • Improvement in insulin function

  • Reduction in oxidative stress

  • SSD in BDI score in the treated group (p = 0.001)

 [47]
Prospective open-label trial 40 patients with treatment-resistant major depressive disorder (mean age, 44.2 ± 15.6 years) Clostridium butyricum MIYAIRI 588 (CBM588) (20 mg orally/twice a day for the first week; 20 mg orally/three times a day from weeks 2 to 8) 8 weeks

  • Significant improvement in depression (greater treatment efficacy in patients with a lack of response to previous antidepressants)

  • SSD in BDI score in the study group (p < 0.001)

 [54]
Open-label single-arm study 29 outpatients with schizophrenia with anxiety and depressive symptoms (mean age, 45 (16) years) Bifidobacterium breve A-1 (5.0 × 1010 CFU) (2 sachets per day) 8 weeks (active intervention administered for 4 weeks)

  • Potential effect in improving anxiety and depressive symptoms

  • SSD in 2 scores at 4 weeks (p = 0.037; p = 0.004) and in 1 score during the post-observation period (p = 0.004)

 [57]
Three-arm parallel design, placebo-controlled, double-blind randomized controlled trial 81 patients with mild to moderate major depression (mean age, 36.5 ± 8.03 years) Lactobacillus helveticus R0052 and
Bifidobacterium longum R0175 (≥10 × 109 CFU) (1 sachet per day)		 8 weeks

  • Improved depression symptoms

  • Decreased serum kynurenine/tryptophan ratio

  • SSD in BDI score in the treated group (p = 0.008)

 [61]
Double-blind, placebo-controlled, single-center, parallel design randomized controlled trial 110 patients with a diagnosis of major depression (mean age, 36.15 ± 7.85 years) Lactobacillus helveticus R0052 and
Bifidobacterium longum R0175 (≥10 × 109 CFU) (1 sachet per day)		 8 weeks

  • Significant decrease in BDI score

  • No effect on inflammatory marker levels

  • Secrease in urinary cortisol levels

  • SSD in BDI score in the treated group (p = 0.04)

 [60]
Double-blind, randomized controlled trial 78 patients with low to moderate depression (mean age, 36.0 ± 9.0 years) Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (≥10 × 109 CFU) (1 sachet per day) 8 weeks

  • Improved depression symptoms

  • SSD in BDI score in the treated group (p = 0.012)

 [62]
Randomized, triple blind, controlled placebo trial 71 participants with mild to severe depression (mean age, 36.65 ± 11.75 years in probiotic group) Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52,
Lactobacillus acidophilus W37,
Lactobacillus brevis W63,
Lactobacillus casei W56,
Lactobacillus salivactocarius W56, Lactobacillus casei W56,
Lactococcus lactis W19, and
Lactococcus lactis W58 (total cell count
1 × 1010 CFU) (2 sachets per day)		 2 months

  • Reducing symptoms of depression, anxiety, and stress

  • Lowering the depression sensitivity marker

  • Changing the classification of depression from clinical to subclinical in the research group

  • No changes in the composition of the microbiota

  • SID in 3 scores in the treated group compared to the placebo group (each p > 0.05)

 [43]
Double-blind, randomized, placebo controlled trial 79 participants with major depressive disorder (mean age, 39.13 ± 9.96 years in probiotic group) Lactobacillus plantarum 299v (1 × 109 CFU) (2 capsules per day) 8 weeks

  • Improvement in cognitive performance

  • Decreased concentration of kynurenic acid

  • SID in 3 scores in the study group (p = 0.797; p = 0.218; p = 0.369)

 [64]
Single-center uncontrolled trial 83 patients with symptoms suggesting anxiety/depression (mean age, 43.9 ± 12.3 years) Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58 (over 2.5 × 109 CFU/g) (1 sachet per day) 8 weeks

  • Anxiety and depression symptoms significantly improved

  • SID in tested score in the study group (p < 0.001)

 [58]
Open-label exploratory study 10 participants in a current episode of MDD (mean age, 25.2 ± 7.0 years) Lactobacillus helveticus
R0052 (90%) and Bifidobacterium longum R0175 (10%) (3 × 109 CFU) (1 sachet per day)		 8 weeks

  • Improved overall mood and anhedonia

  • Reduced anxiety, and improved sleep quality

  • SSD in 2 scores at 4 weeks (both p < 0.001) and SID at 8 weeks (p = 0.377; p = 0.126)

 [59]
Randomized placebo-controlled study 119 participants with a mild or moderate depressive episode (mean age, 32.9 ± 6.1 years) Lactobacillus casei PXN 37, Lactobacillus plantarum PXN 47, Lactobacillus rhamnosus PXN 54, Lactobacillus acidophilus PXN 35, Lactobacillus bulgaricus PXN 39, Lactobacillus helveticus PXN 45, Lactobacillus salivarius PXN 57, Lactobacillus fermentum PXN 44, Lactococcus lactis ssp. Lactis PXN 63, Streptococcus thermophilus PXN 66, Bifidobacterium bifidum PXN 23, Bifidobacterium breve PXN 25, Bifidobacterium longum PXN 30, and Bifidobacterium infantis PXN 27 (2 × 109 CFU)
(3 capsules per day)		 6 weeks

  • Reduction in depression symptoms

  • Decrease in the levels of cortisol, dopamine, IL-6, TNF-α, and NO

  • SID in tested score in the main and the comparison group (p = 0.083)

 [63]
Open trial 11 patients with major depressive disorder (mean age, 39.4 ± 12.0 years) Lactobacillus plantarum PS128 (3 × 1010 CFU) (2 capsules per day) 8 weeks

  • Depressive severity significantly ameliorated

  • Markers of inflammation, gut permeability, and the composition of gutmicrobiota did not significantly change

  • SSD in 2 scores in the study group (p = 0.01; p < 0.001)

 [65]
Double-blind, randomized placebo-controlled trial 61 depressed patients (mean age, 43 ± 14.31 years) Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W22, Lactobacillus casei W56, Lactobacillus paracasei W20, Lactobacillus plantarum W62, Lactobacillus salivarius W24, and Lactobacillus lactis W19 (at least 7.5 × 1012 CFU), and 125 mg of D-Biotin (vitamin B7), 30 mg of common horsetail, 30 mg of fish collagen, and 30 mg of keratin (1 portion per day) 28 days

  • Probiotic therapy might help balance the microbiota composition in individuals with depressive disorders

  • SID in 3 scores in the treated group compared with the placebo group (p = 0.850; p = 0.660; p = 0.631)

 [66]
ALZHEIMER’S DISEASE Randomized, double-blind, placebo-controlled trial 60 patients (mean age, 77.67 ± 2.62 years in probiotic group) Milk (200 mL per day) enriched with probiotic bacteria: Lactobacillus acidophilus, Lactobacillus casei,
Bifidobacterium bifidum, and
Lactobacillus fermentum (2 × 109 CFU/g each)		 12 weeks

  • Improvement in the mental status test

  • Improvement in cognitive functions and selected metabolic indicators

  • No improvement in indicators of oxidative stress and inflammation

  • SSD in MMSE score in the treated group compared with the placebo group (p < 0.001)

 [88]
Randomized, double-blind, placebo-controlled 79 patients (mean age, 76.2 ± 8.1 years in probiotic group) Selenium (200 μg/day) and probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum
(2 × 109 CFU/day each)		 12 weeks

  • Improvement in mental state

  • Reduced levels of CRP protein, insulin, triglycerides, and LDL cholesterol

  • Increase in antioxidant capacity

  • SSD in MMSE score in the treated group compared with the placebo group (p < 0.001)

 [89]
Randomized, double-blind, placebo-controlled trial 48 patients (mean age, 79.70 ± 1.72 years in probiotic group) Two variants of the preparation: Lactobacillus fermentum, Lactobacillus plantarum, and Bifidobacterium lactis, or
Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (each with a total dosage of 3 × 109 CFU) (1 of each capsule per day)		 12 weeks

  • No improvement in cognitive performance or biochemical markers in patients with severe disease

  • SID in tested score in the treated and placebo group (p > 0.05)

 [90]
Uncontrolled clinical trial 13 patients with AD exhibiting cognitive deficit (mean age of women, 78.7 ± 3 years; mean age of men, 78 ± 7 years) Probiotic-fermented milk: pasteurized milk inoculated with 4% kefir grains containing the species Acetobacter aceti, Acetobacter sp., Lactobacillus delbrueckii delbrueckii, Lactobacillus fermentum, Lactobacillus fructivorans, Enterococcus faecium, Leuconostoc spp., Lactobacillus kefiranofaciens, Candida famata, and Candida krusei (2 mL/kg/daily) 90 days

  • Improvement in memory, visual-spatial/abstraction abilities, and executive/language functions

  • SSD in MMSE score in the study group (p < 0.0001)

 [91]
PARKINSON’S DISEASE Open-label, single-arm, baseline-controlled trial 25 patients (mean age, 61.84 ± 5.74 years) Lactobacillus plantarum PS128 (3 × 1013 CFU) (2 capsules per day) 12 weeks

  • Significantly improved UPDRS motor score and quality of life

  • No obvious effect on non-motor symptoms

  • SSD in UPDRS scores in two parameters (p = 0.004; p = 0.012)

 [108]
AUTISM SPECTRUM DISORDER Real-world experience 131 autistic children and adolescents (age: 86.1 ± 41.1 months) Lactobacillus plantarum PS128 (105 patients) (6 × 1010 CFU or 3 × 1010 CFU if patient’s weight was <30 kg) or other probiotics (not listed in the publication) (dose in the recommended range according to age, weight, and specific product) 6 months

  • Significant improvements in terms of global functioning of the patient

  • Greater improvement in neurodevelopmental impairment scores in patients taking Lactobacillus plantarum PS128 than in those taking other probiotics

  • SSD in CGI severity in the study group (p < 0.001)

 [126]
Randomized, double-blind, controlled placebo pilot trial 35 individuals with ASD (mean age, 9.85 ± 4.91 years in probiotic group) Lactobacillus plantarum PS128 (6 × 1010 CFU) (2 capsules per day) and oxytocin from 16 weeks 28 weeks

  • Reduced ASD core socio-behavioral symptoms and clinical global functioning

  • Significant improvements in gut microbiome dysbiosis

  • SID in total scores measured by 2 scales in the study group (p = 0.077; p = 0.26)

  • SSD in 1 score scale in the study group (p <0.05)

 [75]
Randomized, double-blind, controlled placebo trial 63 preschoolers with ASD (mean age, 4.16 ± 1.17 years in probiotic group) “Vivomixx” (Streptococcus thermophilus DSM 24731, Bifidobacterium breve DSM 24732, Bifidobacterium longum DSM 24736, Bifidobacterium infantis DSM 24737, Lactobacillus acidophilus DSM 24735, Lactobacillus plantarum DSM 24730, Lactobacillus paracasei DSM 24733, and Lactobacillus delbrueckii subsp. bulgaricus DSM 24734) (4.5 × 1011 CFU) (2 packets or 1 packet/day in the first and in the following 5 months, accordingly) 6 months

  • No statistically significant changes in autism symptoms between probiotics and placebo group

  • Significant modification of core ASD symptoms in group without gastrointestinal symptoms

  • Alleviation of gastrointestinal symptoms, greater improvements in adaptive functioning, and sensory profiles than in the GI group

  • SID in tested score in the treated and placebo group (p = 0.16)

 [127]
Randomized, double-blind, placebo-controlled study 71 boys with ASD (mean age, 10.01 ± 2.32 years) Lactobacillus plantarum PS128 (PS128) (3 × 1010 CFU/capsule) 4 weeks

  • Mitigation of some autism symptoms (hyperactivity/impulsivity, disruptive and rule-breaking behaviors)

  • SSD in 2 scores in the treated group (p = 0.04; p = 0.02)

  • SID in other 2 scores in the treated group (p = 0.28; p = 0.1) and in 4 scores in the placebo group (p = 0.43; p = 0.2; p = 0.3; p = 0.86)

 [76]
Prospective, open-label study 30 autistic children (mean age, 84.77  ±  16.37 months) Bifidobacterium longum, Lactobacillus rhamnosus, and
Lactobacillus acidophilus (5 × 108 CFU) (1 sachet per day)		 3 months

  • Improvement in the severity of the ASD

  • Positive impact on microbiota composition

  • Reduction in the severity of gastrointestinal symptoms

  • SSD in tested score in the treated group (p = 0.0001)

 [128]

BDI—Beck Depression Inventory; AD—Alzheimer’s disease; ASD—autism spectrum disorder; CFU—colony-forming units; CGI—Clinical Global Impression; CRP—C-reactive protein; GI—gastrointestinal symptoms; IBS—irritable bowel syndrome; LDL—low-density lipoprotein; MDD—major depressive disorder; MMSE—Mini-Mental State Examination; SID—statistically insignificant difference; SSD—statistically significant difference; SSRI—selective serotonin reuptake inhibitor; UPDRS—Unified Parkinson’s Disease Rating Scale.