Search

The maintenance of homeostasis in the gastrointestinal (GI) tract is ensured by the presence of the endocannabinoid system (ECS), which regulates important physiological activities, such as motility, permeability, fluid secretion, immunity, and visceral pain sensation. Beside its direct effects on the GI system, the ECS in the central nervous system indirectly regulates GI functions, such as food intake and energy balance. Mounting evidence suggests that the ECS may play an important role in modulating central neurotransmission which affects GI functioning. It has also been found that the interaction between the ECS and microbiota affects brain and gut activity in a bidirectional manner, and a number of studies demonstrate that there is a strong relationship between GI dysfunctions and mood disorders. Thus, microbiota can regulate the tone of the ECS. Conversely, changes in intestinal ECS tone may influence microbiota composition. In this mini-review, we propose the concept of neuro-gastro-cannabinology as a novel and alternative paradigm for studying and treating GI disorders that affect mood, as well as mood disorders that imbalance GI physiology. This concept suggests the use of prebiotics or probiotics for improving the tone of the ECS, as well as the use of phytocannabinoids or endocannabinoid-like molecules, such as palmitoylethanolamide, to restore the normal intestinal microbiota. This approach may be effective in ameliorating the negative effects of GI dysfunctions on mood and/or the effects of mood disorders on digestive health. Keywords: Cannabinoid treatment, Gut-brain axis, Mood disorders, Gastroinstestinal disorders, Probiotics, Endocannabinoid system, Author(s): Fabio Turco [a]; Viola Brugnatelli [a]; Raquel Abalo [b,c,d] Introduction Homeostasis is derived from the ancient Greek words á½[mu]Î¿Î¹Î¿Ï and ÏÏάÏιÏ, meaning 'staying the same'. As a biological concept, [...]

The embryonic gut tube is a cylindrical structure from which the respiratory and gastrointestinal tracts develop.sup.1. Although the early emergence of the endoderm as an epithelial sheet.sup.2,3 and later morphogenesis of the definitive digestive and respiratory organs.sup.4-6 have been investigated, the intervening process of gut tube formation remains relatively understudied.sup.7,8. Here we investigate the molecular control of macroscopic forces underlying early morphogenesis of the gut tube in the chick embryo. The gut tube has been described as forming from two endodermal invaginations--the anterior intestinal portal (AIP) towards the rostral end of the embryo and the caudal intestinal portal (CIP) at the caudal end--that migrate towards one another, internalizing the endoderm until they meet at the yolk stalk (umbilicus in mammals).sup.1,6. Migration of the AIP to form foregut has been descriptively characterized.sup.8,9, but the hindgut is likely to form by a distinct mechanism that has not been fully explained.sup.10. We find that the hindgut is formed by collective cell movements through a stationary CIP, rather than by movement of the CIP itself. Further, combining in vivo imaging, biophysics and mathematical modelling with molecular and embryological approaches, we identify a contractile force gradient that drives cell movements in the hindgut-forming endoderm, enabling tissue-scale posterior extension of the forming hindgut tube. The force gradient, in turn, is established in response to a morphogenic gradient of fibroblast growth factor signalling. As a result, we propose that an important positive feedback arises, whereby contracting cells draw passive cells from low to high fibroblast growth factor levels, recruiting them to contract and pull more cells into the elongating hindgut. In addition to providing insight into the early gut development, these findings illustrate how large-scale tissue level forces can be traced to developmental signals during vertebrate morphogenesis.Cell-labelling experiments are used to demonstrate that the hindgut in the chick embryo is formed by cells moving through the stationary caudal intestinal portal as a result of a contractile force gradient directed by fibroblast growth factor signalling., Author(s): Nandan L. Nerurkar [sup.1] [sup.6] [sup.7] , ChangHee Lee [sup.1] , L. Mahadevan [sup.2] [sup.3] [sup.4] [sup.5] , Clifford J. Tabin [sup.1] Author Affiliations:(1) Department of Genetics, Harvard Medical [...]

Abstract: Comparative data on the developing gastropod foregut suggest that this multicomponent feeding complex consists of two developmental modules. Modularity is revealed by delayed development of the buccal cavity and [...]

Satiation is the process by which eating and drinking reduce appetite. For thirst, oropharyngeal cues have a critical role in driving satiation by reporting to the brain the volume of fluid that has been ingested.sup.1-12. By contrast, the mechanisms that relay the osmolarity of ingested fluids remain poorly understood. Here we show that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice. We demonstrate that this osmosensory signal is necessary and sufficient for satiation during normal drinking, involves the vagus nerve and is transmitted to key forebrain neurons that control thirst and vasopressin secretion. Using microendoscopic imaging, we show that individual neurons compute homeostatic need by integrating this gastrointestinal osmosensory information with oropharyngeal and blood-borne signals. These findings reveal how the fluid homeostasis system monitors the osmolarity of ingested fluids to dynamically control drinking behaviour. Drinking behaviour in mice is regulated by a signal derived from the water and salt content of the gastrointestinal tract that is transmitted to forebrain neurons that control thirst via the vagus nerve., Author(s): Christopher A. Zimmerman [sup.1] [sup.2] [sup.3] , Erica L. Huey [sup.1] [sup.2] [sup.7] , Jamie S. Ahn [sup.1] [sup.2] [sup.8] , Lisa R. Beutler [sup.2] [sup.4] , Chan Lek [...]

Gut capacity is an important factor in digestive physiology and is often measured as dry matter fill (DMF) following dissection, which prevents repeated measures in the same animal. It was proposed to calculate DMF from food intake, digestibility, and gut mean retention time (MRT), but empirical tests of this are few. We calculated DMF from intake, digestibility, and the MRT of small-particle (1 mm) and large-particle (20 mm) markers in 20 sheep (Ovis aries L., 1758) fed at different intake levels and compared results with DMF at dissection at the end of the feeding trial. MRT for smaller particles was significantly shorter than for larger particles (34.4 ± 6.1 vs. 42.5 ± 7.6 h, respectively). Correspondingly, DMF calculated from smaller particles (0.98 ± 0.27 kg) was significantly lower than DMF calculated from larger particles (1.20 ± 0.30 kg). The latter was not significantly different from DMF measured at dissection (1.18 ± 0.34 kg). These results suggest that DMF can be estimated from measures of digestive physiology. The choice of particle marker to determine MRT is crucial for the accuracy of the proxy. In ruminants, where small particles are consistently eliminated faster than larger particles, considerations of marker particle size are particularly important. Key words: herbivore, ruminant, particle size, passage, gut capacity, sheep, Ovis aries. La capacite du tube digestif, un facteur important en physiologie digestive, est souvent mesuree comme etant le volume de matiere seche (DMF) au moment de la dissection, ce qui empeche des mesures repetees pour le meme animal. S'il a ete propose de calculer le DMF a partir de l'ingestion d'aliments, de la digestibilite et du temps de retention moyen (MRT) dans le tube digestif, il existe peu de tests empiriques. Nous avons calcule le DMF a partir de l'ingestion d'aliments, de la digestibilite et du MRT d'un petit (1 mm) et d'un grand (20 mm) marqueurs particulaires chez 20 moutons (Ovis aries L., 1758) nourris selon differents degres d'ingestion, et compare les resultats avec les DMF mesures apres la dissection a la fin de l'essai d'alimentation. Le MRT pour les petites particules etait significativement plus court que pour les grandes particules (34,4 ± 6,1 contre 42,5 ± 7,6 h, respectivement). Ainsi, le DMF calcule a partir des petites particules (0,98 ± 0,27 kg) etait significativement plus faible que le DMF calcule pour les particules plus grandes (1,20 [+ or -] 0,30 kg), ce dernier n'etant pas significativement different du DMF mesure apres la dissection (1,18 ± 0,34 kg). Ces resultats donnent a penser que le DMF peut etre estime a partir de mesures de la physiologie digestive. Le choix du marqueur particulaire utilise pour determiner le MRT est d'importance cruciale pour l'exactitude de l'estimation. Pour les ruminants, chez lesquels les petites particules sont uniformement eliminees plus rapidement que les particules plus grandes, les considerations touchant a la taille du marqueur particulaire sont particulierement importantes. [Traduit par la Redaction] Mots-cles: herbivore, ruminant, taille des particules, passage, capacite du tube digestif, mouton, Ovis aries., Introduction In the interplay of various anatomical and physiological adaptations that form the digestive strategies of herbivores, gut capacity is an important factor that influences all other measures (Hume 2005; [...]

Tremendous progress has been made in characterizing the bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. A series of provocative preclinical studies have suggested a prominent role for the gut microbiota in these gut-brain interactions. Based on studies using rodents raised in a germ-free environment, the gut microbiota appears to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems. Additionally, microbiota perturbations by probiotics and antibiotics exert modulatory effects on some of these measures in adult animals. Current evidence suggests that multiple mechanisms, including endocrine and neurocrine pathways, may be involved in gut microbiota-to-brain signaling and that the brain can in turn alter microbial composition and behavior via the autonomic nervous system. Limited information is available on how these findings may translate to healthy humans or to disease states involving the brain or the gut/brain axis. Future research needs to focus on confirming that the rodent findings are translatable to human physiology and to diseases such as irritable bowel syndrome, autism, anxiety, depression, and Parkinson's disease., Introduction Alterations in bidirectional brain-gut microbiota interactions are believed to be involved in the pathogenesis of well-known brain-gut disorders such as irritable bowel syndrome (IBS) and related functional gastrointestinal (GI) [...]

Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit's functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems., Introduction Satiety, food preference, and even mood behaviors are a few of the functions modulated by gut chemosensation (1). Ingested nutrients and bacterial by-products contacting the gut epithelium stimulate enteroendocrine [...]