Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Depression is one of the main mental disorders. Pharmacological treatment of depression is often associated with delayed effects or insufficient efficacy. Consequently, there is a need to discover new therapeutic methods to cope with depression faster and more effectively. Several lines of evidence indicate that the use of probiotic therapy reduces depressive symptoms. Nonetheless, the exact mechanisms linking the gut microbiota and the central nervous system, as well as the potential mechanisms of action for probiotics, are still not entirely clarified. The aim of this review was to systematically summarize the available knowledge according to PRISMA guidelines on the molecular mechanisms linking probiotics and healthy populations with subclinical depression or anxiety symptoms, as well as depressed patients with or without comorbid somatic illnesses. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated. Twenty records were included. It has been found that probiotic administration is linked to a significant increase in BDNF levels during probiotic treatment compared to the placebo (SMD = 0.37, 95% CI [0.07, 0.68], p = 0.02) when considering the resolution of depressive symptoms in depressed patients with or without comorbid somatic illnesses. CRP levels were significantly lower (SMD = −0.47, 95% CI [0.75, −0.19], p = 0.001), and nitric oxide levels were significantly higher (SMD = 0.97, 95% CI [0.58, 1.36], p < 0.0001) in probiotic-treated patients compared to the placebo, however, only among depressed patients with somatic co-morbidities. There were no significant differences in IL-1β, IL-6, IL-10, TNF-α, and cortisol levels after probiotic administration between the intervention and control groups (all p > 0.05). Firm conclusions on the effectiveness of probiotics and their possible association with inflammatory markers in the healthy population (only with subclinical depressive or anxiety symptoms) cannot be drawn. The advent of clinical trials examining the long-term administration of probiotics could evaluate the long-term effectiveness of probiotics in treating depression and preventing its recurrence.

The Role of Bifidobacterium bifidum novaBBF7, Bifidobacterium longum novaBLG2 and Lactobacillus paracasei TJB8 to Improve Mechanisms Linked to Neuronal Cells Protection against Oxidative Condition in a Gut-Brain Axis Model

“…A novel strategy to repristinate the gastrointestinal flora is the administration of probiotics, which are good living and transient entities that affect different pathways. Consuming probiotics has been demonstrated to enhance the expression of brain-derived neurotrophic factor (BDNF), a growth factor essential for memory, brain plasticity, and neuronal health that is severely low in depressed people [15][16][17]. Specifically, probiotics promote gut eubiosis and prevent cognitive function decline by decreasing amyloid-Beta (Aβ) levels in the hippocampus, reducing neuroinflammation, and maintaining neuronal structural integrity and plasticity [18].…”

Probiotics and Prebiotics Affecting Mental and Gut Health

“…The review underscored the potential benefits of probiotics in managing depression and anxiety symptoms, particularly in individuals with concomitant somatic disorders. Also, complex interactions between the gut microbiota, immune response, and brain function were highlighted, providing information about prospective treatment options for mental health problems [ 33 ]. The effects of probiotics on the microbiota–gut–brain axis show potential as a complementary treatment for some psychiatric disorders, particularly depression.…”

The Impact of Early-Life Cecal Microbiota Transplantation on Social Stress and Injurious Behaviors in Egg-Laying Chickens

“…Both human and rodent studies indicated that probiotics reduce chronic-psychological-stress-induced abnormal brain activity and related cognitive dysfunctions by lowering plasma CORT and adrenocorticotropic hormone levels, restoring hippocampal 5-HT and NE levels, and normalizing immunity with low plasma levels of TNF-α but high levels of IL-10, an anti-inflammatory cytokine [ 171 , 172 , 173 ]. Several probiotics, as psychobiotics, for example, Bifidobacterium and Lactobacillus , deliver mental health benefits with neurobehavioral effects, which have been used in humans for improving cognitive function and for preventing and treating patients with behavioral impairment in neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, and in diseases with neuropsychiatric disorders, such as anxiety, depression, and impulsively and compulsively disrupted social behavior [ 75 , 77 , 78 , 79 , 83 , 84 ]. Based on findings, targeting the gut microbiota has been recognized as a novel therapeutic option for patients with neuropsychiatric disorders [ 63 , 73 , 74 ].…”

“…Targeting the intestinal microbiota with the goal of restoring its balance has been recognized as a novel therapeutic option for patients with neuropsychiatric disorders [ 72 , 73 , 74 ]. Several probiotics, as psychobiotics, such as Bifidobacterium and Lactobacillus , which can benefit mental health, have been used for preventing and treating patients with behavioral impairment, such as anxiety, depression, and impulsively and compulsively disrupted social behavior, via regulating the MGB, MGI, or both axes [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. However, the use of purified probiotics benefits has shown mixed results, with several weaknesses including transient beneficial effects, requiring continuous administration over time due to the host’s resident microbial populations and “colonization resistance” [ 85 ].…”