Table 2.

Effect of probiotics on depressive symptoms in adults with MDD.

Intervention	Participants	Results
8 week RCT; Probiotic as stand-alone intervention.
One daily capsule containing:	40 adults with MDD, aged 20–55 years.	•Participants in probiotic (Lactobacillus acidophilus; Lactobacillus casei; Bifidobacterium bifidum) group had a significant decrease in BDI total score between time-points compared with the decrease observed in placebo group.
Lactobacillus acidophilus (2 × 109 CFU/g);
Lactobacillus casei (2 × 109 CFU/g), Bifidobacterium bifidum (2 × 109 CFU/g).	Placebo group: 36.2 ± 8.2 yo
Akkasheh et al. (2016)	Probiotic group: 38.3 ± 12.1 yo
90 day RCT; Probiotic as stand-alone intervention.	40 adults with MDD experiencing IBS symptoms, aged 20–65 years.	•Participants in B. coagulans MTCC 5856 group had significant decreases in HAM-D score, MADRS score, and CES-D score between time-points. •Decreases in HAM-D score and MADRS score among probiotic group were significant compared to placebo group (decrease in CES-D score in probiotic group borderline significant compared to placebo group).
One daily capsule containing: B. coagulans MTCC 5856 (2 × 109 CFU/g).	Placebo group: 43.88 ± 9.85 yo
Majeed et al. (2018)	Probiotic group: 40.36 ± 10.28 yo
	110 adults with MDD, aged 18–50 years	•Participants in probiotic (L. helveticus R0052 and B. longum R0175) group had a significant decrease in BDI score compared to probiotic and placebo groups. •Partial Eta square = .09.
8 week RCT; Probiotic as stand-alone intervention.	Placebo group: 36 ± 8.47 yo
Probiotic (L. helveticus R0052 and B. longum R0175, 10 × 109 CFU per 5 g sachet), prebiotic (galactooligosaccharide) or placebo.	Probiotic group: 36.15 ± 7.8) yo
Kazemi et al. (2019)	Prebiotic group: 37.35 ± 7.97 yo
8 week open-label pilot study; Probiotic as stand-alone intervention.		•Probiotic use (L. helveticus R0052 and B. longum R0175) was associated with significant reductions in MADRS, QIDS-SR16, and SHAPS scores between time-points.
L. helveticus R0052 (90%) and B. longum R0175 (10%)	10 treatment-naïve MDD patients, aged 18–65 yo
1.5 g sachets at a dose of 3 × 109 CFU per sachet
Wallace et al. (2021)	Mean participant age: 25.2 ± 7 yo
Probiotics as adjunctive agents in adults with treatment-resistant depression (TRD)
8-week open-label study; probiotic as adjuvant treatment to antidepressant.	40 adults with TRD – defined as inadequate or nonresponse to 2 or more 8-week trials with 2 different classes of antidepressants.	•Participants in probiotic (CBM588) group had significant reductions in HAMD-17, BDI, and BAI scores between time-points. •In probiotic group: 70.0% of patients were considered to be responders (reduction of 50% or greater in HAMD-17 total score), and remission rate was 35.0% (HAMD-17 score of 7 or less at end of treatment).
C. butyricum MIYAIRI 588 (CBM588).20 mg orally BID ×1 week, 20 mg orally TID from weeks 2–8.	CBM588 group (probiotic + antidepressant): 44.2 ± 15.6 yo
Miyaoka et al. (2018)	Control group (antidepressant alone): 41.9 ± 14.2 yo
8-week open label study; probiotic as adjuvant treatment to antidepressant.		•Participants in probiotic (Lactobacillus acidophilus; Bifidobacterium bifidum; Streptoccocus thermophiles) group had significant reduction in BDI and OQ45 scores between time-points.
Combination of probiotic (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptoccocus thermophiles, 2 × 1010 CFU) and magnesium orotate 1600 mg divided in two daily doses.	12 adults with TRD; mean age = 49.3 ± 10.9 yo
Bambling et al. (2017)	Mean years of MDD = 19.8 yo