Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review

Huiying Wang, In-Seon Lee, Christoph Braun, Paul Enck, Huiying Wang, In-Seon Lee, Christoph Braun, Paul Enck

Abstract

To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum, B. breve , and B. infantis ) and Lactobacillus (eg, L. helveticus , and L. rhamnosus ), with doses between 10⁸ and 10¹⁰ colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future.

Keywords: Animals; Anxiety; Depression; Humans; Probiotics.

Figures

Figure 1
Figure 1
Mechanisms of probiotic effects on the central nervous system. Probiotics influence central nervous system (CNS) function through direct and indirect mechanisms. Probiotics affect the hypothalamic-pituitary-adrenal (HPA) axis, by altering corticosteroid (CORT) and/or adrenocorticotropic hormone (ACTH) levels. The immune system is influenced by limited pro-inflammatory cytokine production and inflammation, and this, in turn, has effects on the CNS. Probiotics can also directly alter CNS biochemistry, such as by affecting brain-derived neurotrophic factor (BDNF), c-Fos, γ-aminobutyric acid (GABA), 5 hydroxytryptamine (5-HT), and dopamine (DA) levels, thus influencing mind and behavior. The vagus and enteric nerves are also involved in this gut-brain interaction and are affected by certain probiotics. Probiotics manipulate the gut microbiota (GM) by increasing microbiota diversity and beneficial bacteria composition. An “improved” GM changes metabolites, such as short-chain fatty acids (SCFAs) and tryptophan, and so improves CNS function indirectly. The GM also interacts with the endocrine, immune, and neural systems.
Figure 2
Figure 2
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) scheme of retrieved literature. CNS, central nervous system.

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