MICROBIOTA-GUT-BRAIN AXIS AND PSYCHOBIOTICS: LACTOBACILLUS PLANTARUM PS128 AS AN EXAMPLE
National Yang-Ming University, Taipei City, Taiwan
Increasing evidence indicates that the gut microbiota influences brain development and host behavior through the microbiota-gut-brain axis, which is a bidirectional communication system between the gut microbiota and the brain. This communication system integrates neural, hormonal, and immunological signaling, and can be modulated by a class of probiotics called “psychobiotics”; therefore, these probiotics may be exploited to treat a broad spectrum of complex central nervous system diseases, including irritable bowel syndrome (IBS), mental illness, and neurological disorders. In our previous screening for novel psychobiotics, a candidate strain, PS128, was isolated from Fu-Tsai, a traditional fermented mustard product in Taiwan. Strain PS128, identified later as Lactobacillus plantarum, can increase the locomotor activity of naïve mice in the open field test, and exerts a high anti-inflammatory activity in the dextran sulphate sodium-induced colitis animal model. Here we describe the psychobiological effects of PS128 in germ-free mice, a maternal separation (MS) mouse model of depression, and a rat model of IBS.
In the MS mouse model, C57BL/6J neonates were separated from their mothers and littermates for 3 hours per day between postnatal day (PD) 2 and PD 14. The MS mice were administered with PS128 from the age of 4 to 8 week old and then underwent behavioral tests. Moreover, blood and specific brain regions were collected immediately after sacrifice for further analysis. Eight-week-old C57BL/6J germ-free male mice were daily administered with PS128 for 2 weeks and then subjected to behavior tests and analysis as the MS mice. The IBS-like model was established by 5-Hydroxytryptophan (5-HTP), which was injected subcutaneously into awake Sprague-Dawley rats to induce visceral hypersensitivity. The rats were orally administered with PS128 for 2 weeks. The visceromotor responses were measured after colorectal distension (CRD) to assess visceral hypersensitivity. CRD with simultaneous electromyography recording was done 30 minutes before and 30 minutes after 5-HTP injection. After finishing CRD test, rats were sacrificed in order to take out brain tissue, distal colon, L6-S1 spinal cord, dorsal root ganglion and blood for further analysis.
In both germ-free and MS mice, PS128 administration significantly reduced depression-like behaviors; PS128-treated mice also showed increased contents of dopamine and serotonin in the prefrontal cortex, elevated serum IL-10, and reduced levels of serum corticosterone, TNF-α, and IL-6. In the IBS model, PS128 administration significantly reduced the 5-HTP-induced visceral hypersensitivity, and alleviated the problem of alteration of the stress-related neuromodulator repertoire, including SP, BDNF, CGRP and NGF in dorsal root ganglia and the spinal cord, dopamine and serotonin in the prefrontal cortex, glucocorticoid receptor and mineralocorticoid receptor in the amygdala, and corticosterone in the serum.
Our data suggest that Lactobacillus plantarum PS128 is a psychobiotic. Daily intake of PS128 can help lessen stress-induced neuromodulator and behavioral dysfunctions. Administration of PS128 may be a promising therapeutic approach for neuropsychiatric disorders.
Keywords: Microbiota-Gut-Brain Axis, Probiotics, Psychobiotics, Depression, Irritable Bowel Syndrome, Dopamine
Tsai Y. (2016). Microbiota-gut-brain Axis and psychobiotics: Lactobacillus plantarum PS128 as an example. Conference Proceedings of IPC2016. Paper presented at the International Scientific Conference on Probiotics and Prebiotics, Budapest (p. 121.). IPC2016