Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut–brain axis

Abstract

The gut–brain axis refers to the bidirectional communication between the gut and the brain. Four information carriers (vagal and spinal afferent neurons, immune mediators such as cytokines, gut hormones and gut microbiota-derived signalling molecules) transmit information from the gut to the brain, while autonomic neurons and neuroendocrine factors carry outputs from the brain to the gut. The members of the neuropeptide Y (NPY) family of biologically active peptides, NPY, peptide YY (PYY) and pancreatic polypeptide (PP), are expressed by cell systems at distinct levels of the gut–brain axis. PYY and PP are exclusively expressed by endocrine cells of the digestive system, whereas NPY is found at all levels of the gut–brain and brain–gut axis. The major systems expressing NPY comprise enteric neurons, primary afferent neurons, several neuronal pathways throughout the brain and sympathetic neurons. In the digestive tract, NPY and PYY inhibit gastrointestinal motility and electrolyte secretion and in this way modify the input to the brain. PYY is also influenced by the intestinal microbiota, and NPY exerts, via stimulation of Y1 receptors, a proinflammatory action. Furthermore, the NPY system protects against distinct behavioural disturbances caused by peripheral immune challenge, ameliorating the acute sickness response and preventing long-term depression. At the level of the afferent system, NPY inhibits nociceptive input from the periphery to the spinal cord and brainstem. In the brain, NPY and its receptors (Y1, Y2, Y4, Y5) play important roles in regulating food intake, energy homeostasis, anxiety, mood and stress resilience. In addition, PP and PYY signal to the brain to attenuate food intake, anxiety and depression-related behaviour. These findings underscore the important role of the NPY-Y receptor system at several levels of the gut–brain axis in which NPY, PYY and PP operate both as neural and endocrine messengers.

Neuropeptides and the Microbiota-Gut-Brain Axis

“…Apart from the autonomic regulation of digestion by the central, parasympathetic, sympathetic and enteric nervous systems as well as by neuroendocrine factors (derived from the adrenal medulla and cortex), there is ongoing communication from the gut to the brain in health and disease [5,6]. Thus, visceral information is continuously fed into subcortical regions of the brain including the limbic system and the autonomic and neuroendocrine centres [5].…”

“…This information is integrated with other interoceptive information from the body and with contextual information from the environment [5]. Under pathological conditions, the interoceptive input from the periphery may reach the level of consciousness and give rise to the sensation of nausea, discomfort and/or pain [6]. In addition, the brain's output to the gut via autonomic and neuroendocrine pathways may result in gastrointestinal dysfunction.…”

“…The enteroendocrine L cells in the distal ileum and colon represent a distinct example of this interactive relationship. These cells are stimulated by particular nutrients and digestive products, which leads to the release of PYY, glucagon-like peptide-1 (GLP-1) and GLP-2 [6,44,45]. L cells are also stimulated by short chain fatty acids (e.g., acetate, butyrate, propionate), which particular microbes generate by fermentation of otherwise indigestible carbohydrate fibres.…”

“…L cells are also stimulated by short chain fatty acids (e.g., acetate, butyrate, propionate), which particular microbes generate by fermentation of otherwise indigestible carbohydrate fibres. Short chain fatty acids stimulate L cells via activating G proteincoupled receptors such as Gpr41 [6,44,45]. The important role of this microbiota-host interaction is underscored by the finding that colonization of the mouse colon with a fermentative human microbial community increases the plasma level of PYY, an effect that is blunted by knockout of Gpr41 [45].…”

An Experimental Study to Evaluate the Effect of Basti Karma Over Rats: An Evidence Based Ayurveda Therapy for Parkinsons Disease

“…Among the three NK-1 and NK-3 are found in the brain, whereas NK-2 is primarily localized peripherally in smooth muscle of the respiratory, urinary, and gastrointestinal tracts. Neurokinin receptors are localized in a number of different brain areas which are supposed to play major role in anxiety, including the amygdala, hypothalamus, and locus coeruleus 30 . GI tract is known to produce many brain influencing hormones.…”