Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12: 453-466.

Box | The braingut axis is a system of hierarchical homeostatic reflexes

Prefrontal cortex (PFC); input to the insula (INS); anterior cingulate cortex (ACC); periaqueductal grey (PAG); nucleus tractus solitarius (NTS); rostroventrolateral medulla (RVLM); ventromedial medulla (VMM); dorsal motor nucleus of vagus (DMNV); ANS, autonomic nervous system; medullary catecholaminergic nuclei (A1,

Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12: 453-466. Figure | Gut to brain communication. | Endocrine, immune and neuronal afferent signalling from the gut to the CNS.

5-hydroxytryptamine (5-HT); ; spinal, vagal and intrinsic primary afferents (IPANs), enteroendocrine (EE) cells; Enterochromaffin (EC) cells

Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12: 453-466. Figure | Gut to brain communication. | Encoding of multiple luminal signals by EE cells.

GPR40, G protein-coupled receptor 40; T1R, taste receptor type 1 member; TLRs, toll-like receptors; Ggust G protein subunit, gustducin; PLC2, phospholipase C; PIP2, aquaporin PIP2 member; InsP3, Inositol 1,4,5 trisphosphate; [Ca2+]I intracellular calcium concentration; TRPM5, transient receptor potential cation channel subfamily M member 5; VSCC, voltage-sensitive Ca2+ channel; DAG, diacylglycerol; PKC, protein kinase C; GI peptide, gastrointestinal peptide;

Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12: 453-466. Figure | Gutbrain signalling related to food intake.

PFC, prefrontal cortex; OLF, olfaction; aINS, anterior insula; OFC, orbitofrontal cortex; ACC, anterior cingulate cortex; HIPP, hippocampus; AMYG, amygdala; VTA, ventral tegmental area, NAc, nucleus accumbens; LH, lateral hypothalamus; PeF, pernifornical hypothalamus; ARC, arcuate nucleus; AP, area postrema; NTS, nucleus tractus solitarius; cNTS, caudal NTS; rNTS, rostral NTS;

Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12: 453-466. Figure | Gut signalling systems, gut sensations and metarepresentations of such sensations.

OFC, orbitofrontal cortex, AMYG, amygdala; HIPP, hippocampus; aINS, anterior insula; CRF, corticotropin releasing factor; SP, substance P; CKK, cholecystokinin; NPY, neuropeptide Y; PYY, peptide YY

Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12: 453-466. Figure: Interoceptive memeory and prediction error in chronic disease

ANS, autonomic nervous system; ACC, anterior cingulate cortex; AMYG amygdala; HIPP, hippocampus; OFC orbitofrontal cortex; PFC prefrontal cortex.

Amines Acetylcholine Norepinephrine Serotonin (5-hydroxytryptamine) Amino acids y-Aminobutyric acid Purines ATP Gases Nitric oxide Carbon monoxide Peptides Calcitonin generelated peptide Cholecystokinin Galanin Gastrin-releasing peptide Neuromedin U Neuropeptide Y Neurotensin Opioids Dynorphin Enkephalins Endorphins Peptide YY Pituitary adenylyl cyclaseactivating peptide Somatostatin Substance P Thyrotropin-releasing hormone Vasoactive intestinal contractor (an endothelin) Vasoactive intestinal polypeptide

Verdu E, Armstrong D, Murray J. Between celiac disease and irritable bowel syndrome: the no mans land of gluten sensitivity. Am J Gastroenterol 2009

Several studies in patients with IBS have detected low-grade inflammatory changes involving CD3 + cells, mast cells and reduced mucosal expression of SERT (5-HT transporter). Excess serotonin production in response to a carbohydrate meal has also been described and may be a mechanism for dyspeptic symptoms in celiac disease. Prolonged 5-HT activity, owing to reduced SERT activity, would be expected to lead to activation of afferent pathways, increased acetylcholine (Ach) release, and activation of peristaltic and secretory reflexes, which may affect gut function and symptom generation.
Verdu E, Armstrong D, Murray J. Between celiac disease and irritable bowel syndrome: the no mans land of gluten sensitivity. Am J Gastroenterol 2009

Rome II Criteria for IBS Diagnosis

The included patients had suffered from recurrent abdominal discomfort or pain at least 3 days per month in the previous 3 months, associated with 2 or more of the following: (1) improvement with defecation; (2) onset associated with a change in stool frequency; or (3) onset associated with a changein stool appearance.

Longstreth GF; Thompson WG , Chey WD et al. Functional bowel disorders. Gastroenterology 2006 ; 130 : 1480 1 9

[] Gluten-sensitive individuals, who have IBS symptoms and IgG antibodies to gluten, are orphans, living in no man s land, acknowledged neither by functional disease specialists nor by celiac disease specialists. Verdu E, Armstrong D, Murray J.
Between celiac disease and irritable bowel syndrome: the no mans land of gluten sensitivity. Am J Gastroenterol 2009;

A Carroccio, I Brusca, P Mansueto; Fecal Assays Detect Hypersensitivity to Cows Milk Protein and Gluten in Adults With Irritable Bowel Syndrome; Clinical Gastroenterology and Hepatology Volume 9, Issue 11 , Pages 965-971, November 2011

DBPC, double-blind placebo-controlled oral food challenge; FH, food hypersensitivity; IBS, irritable bowel syndrome

The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language. Recent neurobiological insights into this gutbrain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions, including intuitive decision making. Moreover, disturbances of this system have been implicated in a wide range of disorders, including functional and inflammatory gastrointestinal disorders, obesity and eating disorders.
Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12: 453-466.