The effectiveness of a Lactobacillus probiotic on measures of psychosocial health in adults diagnosed with subthreshold depression: a double-blind, randomised, placebo-controlled trial

Depression is the leading cause of disability worldwide(1). The microbiota-gut-brain axis may play a role in the aetiology of depression, and probiotics show promise for improving mood and depressive state(2). Further evidence is required to support mechanisms and in high-risk populations, such as those with sub-threshold depression (which may be 2-3 times more prevalent than diagnosed depression)(3). The aims were to assess the efficacy of a probiotic compared with placebo in reducing the severity of depressive symptoms in participants with subthreshold depression, and to investigate potential mechanistic markers of inflammatory, antioxidant status and stress response. A double-blind, randomised, placebo-controlled trial was conducted in participants meeting diagnosis of subthreshold depression (DSM-5); aged 18-65 years; ≥18.5 kg/m2 body mass index; not taking antidepressants, centrally acting medications, probiotics nor antibiotics for at least 6 weeks. The probiotic (4 × 109 AFU/CFU, 2.5 g freeze-dried powder containing Lactobacillus fermentum LF16 (DSM26956), L. rhamnosus LR06 (DSM21981), L. plantarum LP01 (LMG P-21021), Bifidobacterium longum BL04 (DSM 23233)) or placebo was taken daily for 3-months. Data was collected at 3 study visits (pre-, mid- (6 weeks), post-intervention). Self-reported questionnaires measured psychological symptoms (Beck Depression Inventory, BDI; Hospital Anxiety Depression Scale, HADS) and quality of life. Blood and salivary samples were collected for biomarkers including cortisol awakening response (CAR). General linear models examined within-group and between-group differences across all time points. Thirty-nine participants completed the study (n = 19 probiotic; n = 20 placebo) using intention-to-treat analysis. The probiotic group decreased in BDI score by −6.5 (95% CI −12.3; −0.7) and −7.6 (95% CI −13.4; −1.8) at 6 and 12 weeks, respectively. The HADS-A score decreased in the probiotic group by −2.8 (95% CI −5.2; −0.4) and −2.7 (95% CI −5.1; −0.3) at 6 and 12, respectively. The HADS-D score decreased in the probiotic group by −3.0 (95% CI −5.4; −0.7) and −2.5 (−4.9; −0.2) at 6 and 12 weeks of intervention, respectively. No between group differences were found. There were no changes in perceived stress or quality of life scores. The probiotic group had reduced hs-CRP levels (7286.2 ± 1205.8 ng/dL vs. 5976.4 ± 1408.3; P = 0.003) and increased total glutathione (14.2 ± 8.9 ng/dL vs. 9.3 ± 4.7; P = 0.049) compared to placebo