The neuronal signaling pathwaysmediating communication between the gut and the CNS include the central,autonomic (the sympathetic and parasympathetic nervous system) and entericnervous system (ENS) (Collins et al., 2012). The humangastrointestinal tract contains a large and complex neural network called theenteric nervous system, whose main purposes are to regulate the physiologicalfunctions of the gut and modulate communication between the gut and the centralnervous system, both in the ascending (gut-to-brain) and descending(brain-to-gut) directions (Sharma et al., 2009).

This communication system iscalled the gut–brain axis, which consists of intricate loops of neurologicalreflexes (Mayer, 2011). The gut is innervated by the ENS, comprising of complexnetwork of sensory, motor, and interneurons, which are capable of independentlyregulating basic GI functions (motility, mucous secretion, and blood flow). Dueto the autonomous nature of the ENS, it is often referred to as the ‘brain ofthe gut’ (Moloney et al., 2014). The sympathetic nervous system is primarily involved in theregulation of motility, secretion and bowel transit time, barrier function, andimmune system activation (Cervi et al., 2014). Neuronal circuits facilitate theENS-CNS communication in which the ENS receives input from the brain and viceversa.

Interestingly, the ENS can function autonomously from the CNS, andtherefore it is often referred to as the ‘second brain’ (Collins et al., 2012).The vagus nerve is the major nerve of the parasympatheticnervous system of the ANS and sends information from numerous peripheral organssuch as heart, intestines, pancreas and stomach to the brainstem via sensoryfibers (Arentsen2017). It has established an important pathway for bidirectionalcommunication between the gut microbes and the brain. Several studies indicate that some of the beneficialprobiotic effects depend upon an intact vagus nerve.

Bravo and colleaguesshowed that specific treatment with probiotic Lactobacillus rhamnosus affected neurochemistry i.e. regiondependent alterations in GABA receptor expression in the brain. Oralsupplementation of Lactobacillus rhamnosus has been shown to reduce stress-inducedcorticosterone and anxiety- and depression-related behaviour in mice via thevagal nerve. Usingvagotomized mice the authors showed that the behavioural and neurochemicaleffects of this probiotic required an intact vagus nerve(Bravo et al., 2011). Microbiota can elicit signals via thevagal nerve to the brain and vice versa.

Kunze and colleagues used anotherstrain of Lactobacillus i.e., Lactobacillus reuteri for activationof calcium-dependent potassium channels in a specific subset of enteric neuronsin the colonic mysenteric plexus of Sprague Dawley rats.

Thus point out adirect link between microbiota and the ENS. Anotherstudy demonstrated in a colitis model, probiotic Bifidobacterium longum requiresintegration of vagus nerve was for reducing the anxiety (Bercik et al., 2011b).On the other hand, the same authors found that antibiotic-induced agitation ofthe gut microbiota led to vagus-independent alterations in brain chemistry andbehaviour (Bercik et al., 2011a), indicating that non-neuronal signaling mechanismsmay also play a significant role in the gut microbiota-brain crosstalk.

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