From Probiotics to Psychobiotics: Live Beneficial Bacteria Which Act on the Brain-Gut Axis

Abstract

There is an important relationship between probiotics, psychobiotics and cognitive and behavioral processes, which include neurological, metabolic, hormonal and immunological signaling pathways; the alteration in these systems may cause alterations in behavior (mood) and cognitive level (learning and memory). Psychobiotics have been considered key elements in affective disorders and the immune system, in addition to their effect encompassing the regulation of neuroimmune regulation and control axes (the hypothalamic-pituitary-adrenal axis or HPA, the sympathetic-adrenal-medullary axis or SAM and the inflammatory reflex) in diseases of the nervous system. The aim of this review is to summarize the recent findings about psychobiotics, the brain-gut axis and the immune system. The review focuses on a very new and interesting field that relates the microbiota of the intestine with diseases of the nervous system and its possible treatment, in neuroimmunomodulation area. Indeed, although probiotic bacteria will be concentrated after ingestion, mainly in the intestinal epithelium (where they provide the host with essential nutrients and modulation of the immune system), they may also produce neuroactive substances which act on the brain-gut axis.

Keywords: beneficial bacteria; human health; microbiota; probiotics; psychobiotics.

Figure 1

Regulation and control of neuroimmune axes. The three systems of regulation and control of information between the central nervous system (CNS) and the periphery are the hypothalamic pituitary adrenal (HPA)-axis, the sympatho-adrenal medullary (SAM)-axis and the inflammatory reflex. These systems are permanently sensing through nociceptive receptors and send information in real time to the CNS. ACTH, adrenocorticotropic hormone; NST Nucleus of the solitary tract; LC Locus coeruleus; TNF, tumor necrosis factor; IL, interleukin.

Figure 2

Brain-Gut Axis. The brain-gut axis is essential for the regulation established between the intestine and the brain. It includes the central nervous system and the endocrine and neuroimmune systems; as well as the enteric nervous system. CRH, corticotropin-releasing hormone; CRF, corticotropin releasing factor; SCFAs, short chain fatty acids; ACTH, adrenocorticitropic hormone; HPA, hypothalamic pituitary adrenal.

Figure 3

Serotoninergic system. The serotoninergic system is involved in the pathogenesis of diseases at the intestinal level, as well as in the regulation of different functions at a systemic level, which includes the regulation of memory processes, cognition and humor, among others. CNS, central nervous system; 5-HT, serotonin; ENS, enteric nervous system.

Figure 4

Brain-Gut Homeostasis. The relationship between the intestine and the brain involves signaling pathways at a neural, metabolic, hormonal and immune system levels. The alteration in these pathways is capable of causing changes in cognitive and behavioral processes, as well as inducing inflammatory processes at the periphery level.

Figure 5

Chronic stress and HPA axis. A chronic stress process is capable of causing disruption at a level of the intestinal barrier and cause dysbiosis, which in turn induces the leakage of bacteria and the activation of the local immune system, leading to a significant alteration of the hypothalamic pituitary adrenal (HPA)-axis. IL, interleukin; MCP-1, monocyte chemoattractant protein; red arrow down mean decrease levels; blue arrow up mean increase levels.

Figure 6

BDNF release system. The brain-derived neurotrophic factor (BDNF) released via the activation of the brain-gut axis has been associated with cognitive and behavioral processes, as well as with anxiolytic and antidepressive effects. SCFAs, short chain fatty acids; red arrow up mean increase levels.