https://www.cell.com/trends/neurosciences/pdf/S0166-2236(13)00008-8.pdf

Gut-brain axis: how the microbiome influences anxiety and depression

The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders

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 gut-brain 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.

/pdf/gut-feelings-the-emerging-biology-of-gut-brain-communication-492090drc0.pdf

Gut feelings: the emerging biology of gut–brain communication

Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes.

/pdf/gastrointestinal-regulation-of-food-intake-jydwlyfm04.pdf

Gastrointestinal regulation of food intake

The results of neural tracing studies suggest that vagal afferent fibers in cervical and thoracic branches innervate the esophagus, lower airways, heart, aorta, and possibly the thymus, and via abdominal branches the entire gastrointestinal tract, liver, portal vein, billiary system, pancreas, but not the spleen. In addition, vagal afferents innervate numerous thoracic and abdominal paraganglia associated with the vagus nerves. Specific terminal structures such as flower basket terminals, intraganglionic laminar endings and intramuscular arrays have been identified in the various organs and organ compartments, suggesting functional specializations. Electrophysiological recording studies have identified mechano- and chemo-receptors, as well as temperature- and osmo-sensors. In the rat and several other species, mostly polymodal units, while in the cat more specialized units have been reported. Few details of the peripheral transduction cascades and the transmitters for signal propagation in the CNS are known. Glutamate and its various receptors are likely to play an important role at the level of primary afferent signaling to the solitary nucleus. The vagal afferent system is thus in an excellent position to detect immune-related events in the periphery and generate appropriate autonomic, endocrine, and behavioral responses via central reflex pathways. There is also good evidence for a role of vagal afferents in nociception, as manifested by affective-emotional responses such as increased blood pressure and tachycardia, typically associated with the perception of pain, and mediated via central reflex pathways involving the amygdala and other parts of the limbic system. The massive central projections are likely to be responsible for the antiepileptic properties of afferent vagal stimulation in humans. Furthermore, these functions are in line with a general defensive character ascribed to the vagal afferent, paraventricular system in lower vertebrates.

Functional and chemical anatomy of the afferent vagal system.

To evaluate the separate contributions of distension and nutrient stimulation of the stomach to the inhibition of short-term food intake and, particularly, to reassess previous analyses based on the inflatable gastrointestinal cuff, four experiments were performed. Rats equipped with pyloric cuffs and indwelling gastric catheters consumed a liquid diet ad libitum. Their consumption during short-term (30 min) feeding bout was measured after gastric infusions on cuff-open and cuff-closed trials. Animals taking meals (approximately 5 ml) with cuffs closed immediately after receiving intragastric infusions of 2.5, 5, 7.5, or 10 ml of normal saline exhibited both suppression at the smallest infusion and a dose-dependent reduction across the other volumes (experiment 1). Additionally, when the test diet concentration was varied, animals with their cuffs closed consumed a constant volume, not a constant number of calories (experiment 2). Furthermore, cuff-closed animals exhibited no more suppression to 5-ml intragastric infusions of nutrients (including, on different trials, 50 and 100% Isocal diet; 10, 20, and 40% glucose; and 40% sucrose and 40% fructose) than to the same volume of saline (experiments 3 and 4). In contrast, on cuff-open trials in which gastric contents could empty into the duodenum, these same nutrient loads were more effective (except fructose) than saline in producing suppression of food intake. In summary, although both limited gastric distension with the pylorus occluded and intestinal nutrient stimulation with the cuff open effectively reduced intake, cuff-closed gastric loads of mixed macronutrients or carbohydrate solutions of 2-8 kcal, pH from 5.8 to 6.7, and osmolarities between 117 and 2,294 mosM/kg produced only the distension-based suppression generated by the same volume of saline.

Gastric volume rather than nutrient content inhibits food intake

Tension and stretch receptors in gastrointestinal smooth muscle: re-evaluating vagal mechanoreceptor electrophysiology.

The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic projections, including sympathetic and parasympathetic efferents as well as visceral afferents, all of which are compromised by age to different degrees. In the present review, we summarize and illustrate key structural changes in the aging innervation of the gut, and suggest a provisional list of the general patterns of aging of the GI innervation. For example, age-related neuronal losses occur in both the myenteric plexus and submucosal plexus of the intestines. These losses start in adulthood, increase over the rest of the life span, and are specific to cholinergic neurons. Parallel losses of enteric glia also occur. The extent of neuronal and glial loss varies along an oral-to-anal gradient, with the more distal GI tract being more severely affected. Additionally, with aging, dystrophic axonal swellings and markedly dilated varicosities progressively accumulate in the sympathetic, vagal, dorsal root, and enteric nitrergic innervation of the gut. These dramatic and consistent patterns of neuropathy that characterize the aging autonomic nervous system of the GI tract are candidate mechanisms for some of the age-related declines in function evidenced in the elderly.

Robert J. Phillips

Papers

Gastric volume rather than nutrient content inhibits food intake

Tension and stretch receptors in gastrointestinal smooth muscle: re-evaluating vagal mechanoreceptor electrophysiology.

Innervation of the gastrointestinal tract: patterns of aging

Gastric satiation is volumetric, intestinal satiation is nutritive

Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: autonomic pathway implicated in Parkinson's disease?