Neuropeptides and the Microbiota-Gut-Brain Axis

Abstract

Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gutbrain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gutbrain axis address 4 information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and 4 information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G proteincoupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are likely to emerge as neural and endocrine messengers in orchestrating the microbiotagut-brain axis in health and disease.

Irritable bowel syndrome, the microbiota and the gut-brain axis

“…Work productivity is mainly dertermined by overall measures of symptom intensity such as Visual Analog Scale (VAS), anxiety and other extra-intestinal symptoms, but not to any single bowel symptom. 14,15 Burden of Illness studies in the US estimate that there are 3.6 million physician visits for IBS annually, and that IBS care consumes over $ 20 billion in both direct and indirect expenditures. Moreover, patients with IBS consume over 50% more health care resources than matched controls without IBS.…”

“…128 Singalling between the different types of cells and between bacteria and epithelial cells requires the presence of neurotransmitters such as 5-HT, somatostatin, dopamin, neuropeptide Y, peptide YY, cholecystokinin and corticotropin-releasing factor. 14,129 The ENS is often referred to as the second brain and is located within the wall of the digestive tract and protected from the gut lumen by the mucous barrier. The ENS contains thousands of ganglia and approximately 500 million neurons which are more than any other peripheral organ and 5 times as many as the spinal cord.…”

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

“…Communication between the gut microbiota and the brain can occur via multiple routes that include the vagus nerve, gut-secreted neuropeptides, sensory nerves, cytokines, tryptophan, and SCFAs (Holzer and Farzi, 2014). See Figure 1.…”

Bidirectional asymmetry in the neurovisceral communication for the cardiovascular control: New insights

“…Moreover, diff erent types of diets diff erentially infl uence the cardiovascular function (involving the RAS) and the profi le of fatty acids and neuropeptides (including Angs) in the frontal cortex ) aff ecting the cortical functions. In fact, the absence of gut microbiota radically alters the nervous and neuroendocrine responses to stress (Crumeyrolle-Arias et al 2014), suggesting a functional bidirectional relationship between the gut and the brain neuropeptides (Holzer and Farzi 2014). Th is involves brain areas such as the hypothalamus, cortex and the limbic system (Bonaz 2013).…”

“…Some neuropeptides involved are: substance P, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin (Holzer and Farzi 2014), cholecystokinin (Dockray 2013) or Angs (Fandriks 2011). Th e mechanisms by which these neuropeptides may connect bilaterally gut and brain not only include endocrine pathways and the stimulation of aff erent and eff erent neurons (Holzer and Farzi 2014) but also axonal transport of factors that infl uence both gut and brain. In fact, this type of connection is possible as vagal axonal transport of RAS components such as angiotensin II binding sites (Diz and Ferrario 1988), as well as factors such as α-synuclein has been observed directly from gut to brain (Holmqvist et al 2014).…”