2. Probiotics and Brain Health
Physical well-being is important for mental well-being and vice versa. Psychobiotics influence brain–bacteria communications through the enteric nervous system (ENS) and immune system and exert anxiolytic, anti-depressant properties resulting in enormous changes in the cognitive and emotional parameters
[6]. Bacterial genera such as
Lactobacillus, Bifidobacterium, Enterococcus, Streptococcus and
Escherichia commonly influence the bidirectional interactions of the brain and gut system through the production of neurochemicals; they are used as psychobiotics. Unlike conventional probiotics, psychobiotics can synthesize or stimulate the production of various neurotransmitters, anti-inflammatory cytokines, and gastric endocrine hormones
[10]. Balancing and maintaining an individual’s physical and emotional well-being requires two-way communication between the gut and brain, mainly regulated by the gut microbiota. Gut microbiota (GM) is important in neurodevelopmental and neuropsychiatric disorders
[10].
The studies on psychobiotics and psychological illness are very limited. However, employing psychobiotics for treating neuropsychiatric diseases is growing as a new field of interest among neurological researchers: psychobiotics used in the treatment of stress, anxiety and depression and other mood disorders. It was found that psychobiotics reduced the cognitive reactivity to negative mood and improved depressive symptoms, anxiety, and stress response
[11,12][11][12].
The microbial infection could affect mental processes, and the metabolically active multifaceted healthy intestinal microbiota provides positive mental health benefits
[8]. Logan and Katzman first used probiotics as an adjunct therapy in managing major depressive disorder (MDD). In MDD, gut microflora becomes altered, and the levels of Lactobacilli and
Bifidobacterium are lower, which could change the gut functions through elevated pro-inflammatory cytokines and oxidative stress. Probiotics could lower the pro-inflammatory cytokines, reduce oxidative stress, and increase BDNF
[13].
GABA is the inhibitory neurotransmitter that plays a significant role in physiological and psychological functions. GABA receptors are important for normal behaviour. More specifically, GABA
B receptors play an important role in mood and anxiety disorders. Any changes in the expression of GABA receptors can cause anxiety and depression along with bowel disorders as comorbid conditions
[14].
Lactobacillus rhamnosus (
L. rhamnosus) reduced anxiety in stress-induced hyperthermia (SIH), elevated plus maze test (EPM) and forced swim test (FST) in mice.
L. rhamnosus altered the expression of GABA
B1b receptors in the brain with an increase in cingulate and prelimbic regions and a decrease in the hippocampus, amygdala, and locus coeruleus. GABA
Aα2 was reduced in the prefrontal cortex and amygdala and increased in the hippocampus compared to the control mice.
L. rhamnosus reduced stress-induced corticosterone elevation and depression-related behaviours
[14]. The results indicated that
L. rhamnosus could change neural functions, which causes behavioural and neurological effects. Thus, it can be considered in therapeutic applications against depression.
Gut disorders with comorbid psychiatric conditions increase gut permeability, enhance lipopolysaccharide (LPS) translocation and increase depressive symptoms.
Lactobacillus farciminis suppress acute psychological stress-induced gut permeability by attenuating the hypothalamus–pituitary–adrenal (HPA) axis in rats
[15]. The oral administration of
Lactobacillus increases the GABA, N-acetyl aspartate, and glutamate in the brain of mice
[16].
Bifidobacterium longum (
B. longum) 1714 enhanced the behaviour and cognitive performance in stressed mice
[17]. Psychobiotics benefit neuropsychiatric disorders such as schizophrenia, Tourette’s syndrome, attention deficit hyperactivity disorder (ADHD), AD, PD, ASD, stress, depression, and anxiety
[10]. In addition to neurodegenerative diseases, neurologic injuries such as traumatic brain injury (TBI), ischemic stroke, spinal cord injury (SCI), and haemorrhagic cerebrovascular lesions could cause gut dysbiosis. In another way, any changes in GM can produce proinflammatory cytokines and clotting factors, increasing the risk of neurological injuries
[18].
The interactions between the gut microbiota, gut and CNS are familiarly known as the microbiota–gut–brain axis (MGBA). Dysregulation in MGBA could cause intestinal disorders, stress, anxiety, depression, and other psychiatric disorders
[14]. The emotional state depends on the gastrointestinal (GI) tract function. MGBA dysregulation can cause GI, neuropsychological, and metabolic disorders. The gut–brain interaction can be identified through the relationship between gut dysbiosis and GI and CNS disorders
[19]. MGBA dysregulation increases intestinal permeability, promotes the proinflammatory phase and causes CNS injuries. The systemic inflammation might result in secondary CNS injuries
[20]. High differentiation and migration of immune cells to the CNS can cause maladaptive CNS inflammation
[21], resulting in TBI, SCI, strokes, and brain tumours
[22] (
Figure 21).
Figure 21. The characteristics of the ideal and consequents of dysfunctions of the microbiota–gut–brain axis (MGBA)
[19,20,21,22][19][20][21][22]. (Figure created using
BioRender.com; accessed on 17 October 2022.)
The gut and brain connection are inevitable. The gut is completely innervated and controlled by the neurons of the ENS. The imperial connection was initiated during earlier embryogenesis. The initial neural crest later becomes differentiated into the ENS and CNS. In addition, during development, these two systems are connected by the tenth cranial nerve, the vagus nerve, straight from the brain stem to the abdomen
[23]. In addition to the GI tract, microbiota also colonizes in the nasal region, as the nasal tract is one of the predominant entry sites of microbes. The nasal mucosa encompasses various microbial communities, which determine olfactory health, and CNS function. Nasal microbiota metabolites can enter the brain through the blood–brain barrier and reach the olfactory epithelium or bulb. Any dysbiosis in nasal microbiota can cause olfactory function intrusion; henceforth, olfactory dysfunction is one of the primary indicators of neurological illness
[24].
The human GI tract consists of a collective number of microbial cells. Their metabolites constitute the GM, play a functional role in maintaining physiological and metabolic processes, confer immunity against pathogens
[25], and process the brain functions and behaviour of the host
[26]. GM produces some microbial products through which it becomes more interactive with the host by entering the circulation from the GI tract to all distant organs
[27]. GM responds to diet and exercise and significantly produces changes in the mood and cognition of the host
[28]. GM metabolites react with receptors of the brain and synthesize the neuroactive components that affect the GI and mental health of the host. It is described that probiotics can produce neuroactive chemicals and regulate the functions of the CNS as well as the GI tract through neuronal cells and immune cell receptors
[29].
Probiotics can work both inside and outside of the GI system. While inside the GI system, the probiotics interact with the gut microbes directly or through their enzymes with the intestinal mucosal layer and epithelial layer, which changes the barrier functions and mucosal immune system. Outside the GI system, probiotics interact with other organs, such as the liver and brain
[30]. The ENS and CNS form a complex network that works with the help of neurotransmitters. Any changes in the levels of neurotransmitters can affect CNS function through neuronal signals
[10].