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FROM THE PREFACE:The original purpose of the First Edition of Physiology of the Gastrointestinal Tract?to collect in one set of volumes the most current and comprehensive knowledge in our field?was also the driving force for the Fourth Edition. The explosion of information at the cellular level, made possible in part by the continued emergence of powerful molecular and cellular techniques, has resulted in a greater degree of revision than that of any other edition. The first section, now titled \"Basic Cell Physiology and Growth of the Gl Tract\" contains numerous new chapters on topics such as transcriptional regulation, signaling networks in development, apoptosis, and mechanisms in malignancies. Most of the chapters in this section were edited by Juanita L. Merchant. Section II has been renamed \"Neural Gastroenterology and Motility\" and has been expanded from seven chapters with rather classic titles to more than twenty chapters encompassing not only the movement of the various parts of the digestive tract but also cell physiology, neural regulation, stress, and the regulation of food intake. Almost all of the chapters were recruited and edited by Jackie D. Wood. The third section is entirely new and contains chapters on \"Immunology and Inflammation\" which were edited by Kim E. Barrett. The fourth section on the \"Physiology of Secretion\" consists of chapters with familiar titles, but with completely updated information to reflect the advances in our understanding of the cellular processes involved in secretion. The last section on \"Digestion and Absorption\" contains new chapters on the intestinal barrier, protein sorting and ion channels along with those focusing on the uptake of specific nutrients. These chapters were recruited and edited by Hamid M. Said and Fayez K. Ghishan.

Physiology of the Gastrointestinal Tract, Fifth Edition - winner of a 2013 Highly Commended BMA Medical Book Award for Internal Medicine - covers the study of the mechanical, physical, and biochemical functions of the GI Tract while linking the clinical disease or disorder, bridging the gap between clinical and laboratory medicine. The gastrointestinal system is responsible for the breakdown and absorption of various foods and liquids needed to sustain life. Other diseases and disorders treated by clinicians in this area include: food allergies, constipation, chronic liver disease and cirrhosis, gallstones, gastritis, GERD, hemorrhoids, IBS, lactose intolerance, pancreatic, appendicitis, celiac disease, Crohn's disease, peptic ulcer, stomach ulcer, viral hepatitis, colorectal cancer and liver transplants. The new edition is a highly referenced and useful resource for gastroenterologists, physiologists, internists, professional researchers, and instructors teaching courses for clinical and research students. 2013 Highly Commended BMA Medical Book Award for Internal MedicineDiscusses the multiple processes governing gastrointestinal functionEach section edited by preeminent scientist in the fieldUpdated, four-color illustrations

Functional gastrointestinal (GI) symptoms are common in the general population. Especially, motor dysfunction of the GI tract and visceral hypersensitivity are important. Acupuncture has been used to treat GI symptoms in China for thousands of years. It is conceivable that acupuncture may be effective in patients with functional GI disorders because it has been shown to alter acid secretion, GI motility, and visceral pain. Acupuncture at the lower limbs (ST-36) causes muscle contractions via the somatoparasympathetic pathway, while at the upper abdomen (CV-12) it causes muscle relaxation via the somatosympathetic pathway. In some patients with gastroesophageal reflux disease (GERD) and functional dyspepsia (FD), peristalsis and gastric motility are impaired. The stimulatory effects of acupuncture at ST-36 on GI motility may be beneficial to patients with GERD or FD, as well as to those with constipation-predominant irritable bowel syndrome (IBS), who show delayed colonic transit. In contrast, the inhibitory effects of acupuncture at CV-12 on GI motility may be beneficial to patients with diarrhea-predominant IBS, because enhanced colonic motility and accelerated colonic transit are reported in such patients. Acupuncture at CV-12 may inhibit gastric acid secretion via the somatosympathetic pathway. Thus, acupuncture may be beneficial to GERD patients. The antiemetic effects of acupuncture at PC-6 (wrist) may be beneficial to patients with FD, whereas the antinociceptive effects of acupuncture at PC-6 and ST-36 may be beneficial to patients with visceral hypersensitivity. In the future, it is expected that acupuncture will be used in the treatment of patients with functional GI disorders.

Microorganisms colonize various ecological niches in the human habitat, as they do in nature. Predominant forms of multicellular communities called biofilms colonize human tissue surfaces. The gastrointestinal tract is home to a profusion of microorganisms with intertwined, but not identical, lifestyles: as isolated planktonic cells, as biofilms and in biofilm-dispersed form. It is therefore of major importance in understanding homeostatic and altered host–microorganism interactions to consider not only the planktonic lifestyle, but also biofilms and biofilm-dispersed forms. In this Review, we discuss the natural organization of microorganisms at gastrointestinal surfaces, stratification of microbiota taxonomy, biogeographical localization and trans-kingdom interactions occurring within the biofilm habitat. We also discuss existing models used to study biofilms. We assess the contribution of the host–mucosa biofilm relationship to gut homeostasis and to diseases. In addition, we describe how host factors can shape the organization, structure and composition of mucosal biofilms, and how biofilms themselves are implicated in a variety of homeostatic and pathological processes in the gut. Future studies characterizing biofilm nature, physical properties, composition and intrinsic communication could shed new light on gut physiology and lead to potential novel therapeutic options for gastrointestinal diseases.In this Review, Motta, Vergnolle and colleagues describe the organization of microorganisms into planktonic, biofilm and biofilm-dispersed forms in the gastrointestinal tract. The role of the host–biofilm relationship in gut homeostasis and disease is discussed.

The gastrointestinal tract has recently come to the forefront of multiple research fields. It is now recognized as a major source of signals modulating food intake, insulin secretion and energy balance. It is also a key player in immunity and, through its interaction with microbiota, can shape our physiology and behavior in complex and sometimes unexpected ways. The insect intestine had remained, by comparison, relatively unexplored until the identification of adult somatic stem cells in the Drosophila intestine over a decade ago. Since then, a growing scientific community has exploited the genetic amenability of this insect organ in powerful and creative ways. By doing so, we have shed light on a broad range of biological questions revolving around stem cells and their niches, interorgan signaling and immunity. Despite their relatively recent discovery, some of the mechanisms active in the intestine of flies have already been shown to be more widely applicable to other gastrointestinal systems, and may therefore become relevant in the context of human pathologies such as gastrointestinal cancers, aging, or obesity. This review summarizes our current knowledge of both the formation and function of the Drosophila melanogaster digestive tract, with a major focus on its main digestive/absorptive portion: the strikingly adaptable adult midgut.

The enteric nervous system (ENS) is an extensive network comprising millions of neurons and glial cells contained within the wall of the gastrointestinal tract. The major functions of the ENS that have been most studied include the regulation of local gut motility, secretion, and blood flow. Other areas that have been gaining increased attention include its interaction with the immune system, with the gut microbiota and its involvement in the gut–brain axis, and neuro-epithelial interactions. Thus, the enteric circuitry plays a central role in intestinal homeostasis, and this becomes particularly evident when there are faults in its wiring such as in neurodevelopmental or neurodegenerative disorders. In this review, we first focus on the current knowledge on the cellular composition of enteric circuits. We then further discuss how enteric circuits detect and process external information, how these signals may be modulated by physiological and pathophysiological factors, and finally, how outputs are generated for integrated gut function.

Modern research on gastrointestinal behavior has revealed it to be a highly complex bidirectional process in which the gut sends signals to the brain, via spinal and vagal visceral afferent pathways, and receives sympathetic and parasympathetic inputs. Concomitantly, the enteric nervous system within the bowel, which contains intrinsic primary afferent neurons, interneurons, and motor neurons, also senses the enteric environment and controls the detailed patterns of intestinal motility and secretion. The vast microbiome that is resident within the enteric lumen is yet another contributor, not only to gut behavior, but to the bidirectional signaling process, so that the existence of a microbiota-gut-brain \"connectome\" has become apparent. The interaction between the microbiota, the bowel, and the brain now appears to be neither a top-down nor a bottom-up process. Instead, it is an ongoing, tripartite conversation, the outline of which is beginning to emerge and is the subject of this Review. We emphasize aspects of the exponentially increasing knowledge of the microbiota-gut-brain \"connectome\" and focus attention on the roles that serotonin, Toll-like receptors, and macrophages play in signaling as exemplars of potentially generalizable mechanisms.

Key Points Animals are closely associated with a vast and diverse microbiota, most members of which reside in the gastrointestinal tract. Two gradients of microbial distribution exist in the gastrointestinal tract: the proximal–distal axis and the tissue–lumen axis. Several parameters, including diet, lifestyle, antibiotics and other drugs, hygiene, and the genetics and immune status of the host, shape the microbiota composition, with various consequences for host physiology. The gut microbiota is required for the development and maturation of the intestinal epithelium and immune system of the host. This microbiota affects properties of the mucus layer, promotes the development of lymphoid structures, modulates activation and differentiation of several lymphocyte populations and balances the production of immunoglobulin A and antimicrobial peptides. The gut microbiota facilitates host metabolism and adiposity by expanding nutrient sources, producing essential vitamins and carrying out xenobiotic metabolism, but also affects a wide range of other host physiological aspects, including organ morphogenesis, intestinal vascularization, tissue homeostasis, carcinogenesis, bone mass and behaviour. There is increasing evidence for a tight cross-species homeostatic interaction between the host and its microbiota, and research in this field has been facilitated by recent progress in the description and isolation of gut microbiota members, as well as in gnotobiology and host genetics. Elucidation of the molecular targets and causative connections in these host–microbiota interactions promises to reveal new possibilities to treat chronic inflammatory diseases and maintain human health. The gut microbiota, traditionally studied in the context of disease, has emerged as a key regulator during normal homeostasis. Here, Sommer and Bäckhed discuss how the gut microbiota promotes the development and homeostasis of the immune system and orchestrates several aspects of human physiology, including tissue morphogenesis, metabolism and even behaviour. Establishing and maintaining beneficial interactions between the host and its associated microbiota are key requirements for host health. Although the gut microbiota has previously been studied in the context of inflammatory diseases, it has recently become clear that this microbial community has a beneficial role during normal homeostasis, modulating the host's immune system as well as influencing host development and physiology, including organ development and morphogenesis, and host metabolism. The underlying molecular mechanisms of host–microorganism interactions remain largely unknown, but recent studies have begun to identify the key signalling pathways of the cross-species homeostatic regulation between the gut microbiota and its host.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract 1 – 3 . Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease 1 – 3 . However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain–gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body. NeuroString, a tissue-like biological interface created by laser patterning of polyimide into a graphene/nanoparticle network embedded in an elastomer, is introduced, allowing in vivo real-time detection of neurotransmitters in the brain and gut.

ObjectivesHabitual diet plays a major role in shaping the composition of the gut microbiota, and also determines the repertoire of microbial metabolites that can influence the host. The typical Western diet corresponds to that of an omnivore; however, the Mediterranean diet (MD), common in the Western Mediterranean culture, is to date a nutritionally recommended dietary pattern that includes high-level consumption of cereals, fruit, vegetables and legumes. To investigate the potential benefits of the MD in this cross-sectional survey, we assessed the gut microbiota and metabolome in a cohort of Italian individuals in relation to their habitual diets.Design and resultsWe retrieved daily dietary information and assessed gut microbiota and metabolome in 153 individuals habitually following omnivore, vegetarian or vegan diets. The majority of vegan and vegetarian subjects and 30% of omnivore subjects had a high adherence to the MD. We were able to stratify individuals according to both diet type and adherence to the MD on the basis of their dietary patterns and associated microbiota. We detected significant associations between consumption of vegetable-based diets and increased levels of faecal short-chain fatty acids, Prevotella and some fibre-degrading Firmicutes, whose role in human gut warrants further research. Conversely, we detected higher urinary trimethylamine oxide levels in individuals with lower adherence to the MD.ConclusionsHigh-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet.Trial registration numberThis study was registered at clinical trials.gov as NCT02118857.