Table 2.

Antidepressant efficacy of probiotic supplementation.

Mental Condition	Study Design	Intervention	Main Findings	References
IBS with mild to moderate depression and anxiety	Double-blind RCT. A total of 44 adult patients (age: 26–58 years) with IBS and mild to moderate depression and anxiety were selected.	B. longum (1 × 1010 CFU/g powder) (n = 22) or placebo (n = 22) for 6 weeks.	B. longum reduced depression scores but not anxiety scores with improvements in quality of life.	[101]
MDD	Double-blind RCT. A total of 110 patients were randomized to receive probiotic, prebiotic, or placebo.	Probiotic supplement (L. helveticus R0052 and B. longum R0175), prebiotic (galacto-oligosaccharide), or placebo for 8 weeks.	Probiotic supplementation decreased BDI scores, increased tryptophan/isoleucine ratio, and reduced kynurenine/tryptophan ratio, compared with placebo. No such effects were seen with prebiotics.	[102]
Healthy medical students	Double-blind placebo-controlled trial. Healthy medical students were recruited in the trial to evaluate the effects of probiotic species in the prevention of the onset of physical symptoms.	Fermented milk containing L. casei strain Shirota (n = 24) or placebo (n = 23) for 8 weeks.	Fermented milk reduced the onset of physical symptoms, with a significant elevation of fecal serotonin levels. No difference was found in HADS-anxiety, HADS-depression, SDS, and PSQI scores in both groups.	[103]
Healthy individuals	Triple-blind placebo-controlled randomized pre- and postintervention assessment design. A total of 40 healthy individuals participated in the evaluation of the effects of a multispecies probiotic supplement in the reduction of cognitive reactivity to sad mood.	Multispecies probiotic supplement (B. lactis W52, B. bifidum W23, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W19, and L. lactis W58) or placebo for 4 weeks.	LEIDS-r showed a significant reduction in the cognitive reactivity to depression, in particular, rumination and aggressive thoughts, in the probiotic-supplement-treated group.	[104]
Depressed mood	Double-blind randomized placebo-controlled trial. A total of 132 healthy individuals (mean age: 61.8 years) with poor mood voluntarily participated in the study.	Yoghurt containing L. casei Shirota (108/mL) or placebo for 3 weeks.	Improvement of mood with the consumption of a probiotic-containing yoghurt.	[105]
MDD	Double-blind placebo-controlled randomized clinical trial. A total of 110 patients with MDD (age: 18–50 years) were recruited in the trial.	Probiotic (L. helveticus R0052 and B. longum R0175), prebiotic (galacto-oligosaccharide), or placebo for 8 weeks.	No change in the level of inflammatory markers. Probiotic supplementation significantly decreased urinary cortisol levels and BDI scores. No antidepressant effects were seen with prebiotics.	[106]
MDD	Double-blind placebo-controlled randomized clinical trial. A total of 40 patients with MDD and in the age range of 20–55 years were recruited in the study.	Probiotic supplement containing L. acidophilus (2 × 109 CFU/g), L. casei (2 × 109 CFU/g), and B. bifidum (2 × 109 CFU/g) or placebo for 8 weeks.	Significant improvement in BDI scores, serum insulin concentration, HOMA-IR and hs-CRP, and glutathione concentrations with probiotic administration.	[107]
Depressive symptoms in mild to severe depression	Triple-blind placebo-controlled randomized clinical trial. A total of 71 patients with mild to severe depression were randomized in the intervention (mean age: 36.65 years) or placebo (mean age: 35.49 years) groups.	Ecologic® Barrier (2.5 × 109 CFU/g) containing B. bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W19, and L. lactis W58 (total cell count: 1 × 1010 CFU/day) or placebo for 8 weeks.	Significant improvement of cognitive symptoms in the intervention group as compared with the placebo group, especially in patients with mild to moderate depression. No significant effect on gut microbial alteration.	[108]
Inpatients diagnosed with depression	Randomized double-blind controlled trial. A total of 82 inpatients diagnosed with depression were randomized in the intervention group (n = 42) or placebo (n = 40).	OMNi-BiOTiC® Stress Repair (B. bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W22, L. casei W56, L. paracasei W20, L. plantarum W62, L. salivarius W24, and L. lactis W19) plus 125 mg D-biotin or placebo plus D-biotin for 4 weeks.	No significant differences between both groups in psychiatric symptoms. More abundance of Ruminococcus gauvreauii and Coprococcus 3 strains and elevation of inflammatory regulatory and metabolic pathways in the intervention group.	[110]