# The 2017). It has established an important pathway

The neuronal signaling pathways
mediating communication between the gut and the CNS include the central,
autonomic (the sympathetic and parasympathetic nervous system) and enteric
nervous system (ENS) (Collins et al., 2012). The human
gastrointestinal tract contains a large and complex neural network called the
enteric nervous system, whose main purposes are to regulate the physiological
functions of the gut and modulate communication between the gut and the central
nervous system, both in the ascending (gut-to-brain) and descending
(brain-to-gut) directions (Sharma et al., 2009). This communication system is
called the gut–brain axis, which consists of intricate loops of neurological
reflexes (Mayer, 2011). The gut is innervated by the ENS, comprising of complex
network of sensory, motor, and interneurons, which are capable of independently
regulating basic GI functions (motility, mucous secretion, and blood flow). Due
to the autonomous nature of the ENS, it is often referred to as the ‘brain of
the gut’ (Moloney et al., 2014). The sympathetic nervous system is primarily involved in the
regulation of motility, secretion and bowel transit time, barrier function, and
immune system activation (Cervi et al., 2014). Neuronal circuits facilitate the
ENS-CNS communication in which the ENS receives input from the brain and vice
versa. Interestingly, the ENS can function autonomously from the CNS, and
therefore it is often referred to as the ‘second brain’ (Collins et al., 2012).
The vagus nerve is the major nerve of the parasympathetic
nervous system of the ANS and sends information from numerous peripheral organs
such as heart, intestines, pancreas and stomach to the brainstem via sensory
fibers (Arentsen
2017). It has established an important pathway for bidirectional
communication between the gut microbes and the brain. Several studies indicate that some of the beneficial
probiotic effects depend upon an intact vagus nerve. Bravo and colleagues
showed that specific treatment with probiotic Lactobacillus rhamnosus affected neurochemistry i.e. region
dependent alterations in GABA receptor expression in the brain. Oral
supplementation of Lactobacillus rhamnosus has been shown to reduce stress-induced
corticosterone and anxiety- and depression-related behaviour in mice via the
vagal nerve. Using
vagotomized mice the authors showed that the behavioural and neurochemical
effects of this probiotic required an intact vagus nerve
(Bravo et al., 2011). Microbiota can elicit signals via the
vagal nerve to the brain and vice versa. Kunze and colleagues used another
strain of Lactobacillus i.e., Lactobacillus reuteri for activation
of calcium-dependent potassium channels in a specific subset of enteric neurons
in the colonic mysenteric plexus of Sprague Dawley rats. Thus point out a
direct link between microbiota and the ENS.

Another
study demonstrated in a colitis model, probiotic Bifidobacterium longum requires
integration of vagus nerve was for reducing the anxiety (Bercik et al., 2011b).
On the other hand, the same authors found that antibiotic-induced agitation of
the gut microbiota led to vagus-independent alterations in brain chemistry and
behaviour (Bercik et al., 2011a), indicating that non-neuronal signaling mechanisms
may also play a significant role in the gut microbiota-brain crosstalk.

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