Comparing finite viscoelastic constitutive relations and variational principles in modeling gastrointestinal soft tissue deformation.

The mechanical attributes of soft tissues within the gastrointestinal (GI) tract are crucial for the effective operation of the GI system, and alterations in these properties may play a role in motility-related disorders. Various constitutive modeling approaches have been suggested to comprehend the response of soft tissues to diverse loading conditions. Among these, hyperelastic constitutive models based on finite elasticity have gained popularity. However, these models fall short in capturing rate- and time-dependent tissue properties. In contrast, finite viscoelastic models offer a solution to overcome these limitations. Nevertheless, the development of a suitable finite viscoelastic model, coupled with a variational formulation for efficient finite element (FE) implementation, remains an ongoing challenge. This study aims to address this gap by developing diverse finite viscoelastic constitutive relations and applying them to characterize soft tissue. Furthermore, the research explores the creation of compressible, nearly incompressible, and incompressible versions of viscoelastic constitutive relations, along with their variational formulation, to facilitate efficient FE implementation. The proposed model demonstrates remarkable accuracy in replicating experimental results, achieving an R2 value exceeding 0.99.

Particle size of insoluble fibres and gelation of soluble fibres influence digesta passage rate throughout the gastrointestinal tract of finishing pigs.

Fibres, as abundant in agricultural by-products, exhibit a large range of physicochemical properties that can influence digestive processes such as digesta mean retention time (MRT), thereby affecting nutrient digestion kinetics. In this study, we investigated the effects of particle size of insoluble fibres, and gelation of soluble fibres on MRT of liquids, fine solids, and fibrous particles in the different segments of the gastrointestinal tract (GIT) of pigs. Twenty-four boars (51.6 ± 4.90 kg) were allocated to four diets; two diets contained 15% wheat straw, either coarsely chopped or finely ground (1-mm screen), two diets contained 27% wheat bran without or with the addition of 10% low-methylated pectin. After 14 days of adaptation to the diet, a total collection of faeces was performed to determine the total tract digestibility of nutrients. Thereafter, pigs were fed diets supplemented with tracers for at least 5 days and dissected following a frequent feeding procedure to approach steady-state passage of digesta. The MRT of liquids (Co-EDTA), fine solids (TiO2), and fibrous particles (Chromium-mordanted fibres) in the different segments of the GIT were quantified. In the stomach, particle size reduction of straw decreased the MRT of fine solids by 02:39 h, and fibrous particles by 07:21 h (P < 0.10). Pectin addition to the wheat bran diet reduced the MRT of fine solids by 03:09 h, and fibrous particles by 07:10 h (P < 0.10), but not of liquids, resulting in less separation between digesta phases in the stomach compared with the bran diet (P < 0.05). In the mid-small intestine (SI), pectin addition reduced the MRT of fibrous particles and the separation between fibrous particles and fine solids. No further effects of particle size reduction of straw nor pectin addition on MRT and digestibility of starch, nitrogen, or fat were observed in the SI. In the large intestine (LI), particle size reduction of straw reduced separation between fibrous particles and fine solids (P < 0.10), while pectin addition had no effects. Total tract, non-starch polysaccharide degradation of straw was poor (∼31%), and unaffected by particle size reduction (P > 0.10). The complete fermentation of pectin did not influence the degradation of wheat bran fibres (∼51%). In conclusion, the effects of particle size of insoluble fibres and gelling properties of soluble fibres on the passage of digesta phases were most pronounced in the stomach, but less prominent in distal segments of the GIT.

Neuroimmunophysiology of the gastrointestinal tract.

Gut physiology is the epicenter of a web of internal communication systems (i.e., neural, immune, hormonal) mediated by cell-cell contacts, soluble factors, and external influences, such as the microbiome, diet, and the physical environment. Together these provide the signals that shape enteric homeostasis and, when they go awry, lead to disease. Faced with the seemingly paradoxical tasks of nutrient uptake (digestion) and retarding pathogen invasion (host defense), the gut integrates interactions between a variety of cells and signaling molecules to keep the host nourished and protected from pathogens. When the system fails, the outcome can be acute or chronic disease, often labeled as "idiopathic" in nature (e.g., irritable bowel syndrome, inflammatory bowel disease). Here we underscore the importance of a holistic approach to gut physiology, placing an emphasis on intercellular connectedness, using enteric neuroimmunophysiology as the paradigm. The goal of this opinion piece is to acknowledge the pace of change brought to our field via single-cell and -omic methodologies and other techniques such as cell lineage tracing, transgenic animal models, methods for culturing patient tissue, and advanced imaging. We identify gaps in the field and hope to inspire and challenge colleagues to take up the mantle and advance awareness of the subtleties, intricacies, and nuances of intestinal physiology in health and disease by defining communication pathways between gut resident cells, those recruited from the circulation, and "external" influences such as the central nervous system and the gut microbiota.

In vitro gastrointestinal simulated digestion of three plant proteins: determination of digestion rate, free amino acids and peptide contents.

Cassava protein (CP), barley protein (BP) and yellow pea protein (YPP) are important nutrient and integral constituent of staple in pet foods. It is known that the digestion of proteins directly influences their absorption and utilisation. In the present work, we performed in vitro simulated gastrointestinal digestion of three plant proteins as a staple for dog and cat food. The digestion rate of CP, BP and YPP in dog food was 56.33 ± 0.90%, 48.53 ± 0.91%, and 66.96 ± 0.37%, respectively, whereas the digestion rate of CP, BP, and YPP in cat food was 66.25 ± 0.72%, 43.42 ± 0.83%, and 58.05 ± 0.85%, respectively. Using SDS-polyacrylamide gel electrophoresis to determine the molecular weight (MW) of each protein and the products of their digestion, it was revealed that MW of digestion samples decreased, and MW during the small intestine phase was lower than that during the gastric phase. Peptide sequences of digested products were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and it was found that the total number of peptides in the small intestine digestion samples was higher than that in the gastric phase samples. The MW of peptides obtained from CP was within the range of 1000-1500 Da, while MW of peptides derived from BP and YPP was within the range of 400-2000 Da. In addition, free amino acids were mainly produced in the small intestine phase. Furthermore, the percentage of essential amino acids in the small intestine phase (63 ~ 82%) was higher than that in the gastric phase (37 ~ 63%). Taken together, these findings contribute to the current understanding of the utilisation of plant proteins in dog and cat foods and provide important insights into the selection and application of plant proteins as a staple in dog and cat foods.

The impact of 48 h high carbohydrate diets with high and low FODMAP content on gastrointestinal status and symptoms in response to endurance exercise, and subsequent endurance performance.

This study investigated the effects of a high carbohydrate diet, with varied fermentable oligo-, di-, and mono-saccharide and polyol (FODMAP) content, before endurance exercise on gastrointestinal integrity, motility, and symptoms; and subsequent exercise performance. Twelve endurance athletes were provided with a 48 h high carbohydrate (mean ± SD: 12.1 ± 1.8 g kg day-1) diet on two separate occasions, composed of high (54.8 ± 10.5 g day-1) and low FODMAP (3.0 ± 0.2 g day-1) content. Thereafter, participants completed a 2 h steady-state running exercise at 60% of V ˙ O 2 max (22.9 ± 1.2 °C, 46.4 ± 7.9% RH), followed by a 1 h distance performance test. Pre-exercise and every 20 min during steady-state exercise, 100 mL maltodextrin (10% w/v) solution was consumed. A 150 mL lactulose (20 g) solution was consumed 30 min into the distance performance test to determine orocecal transit time (OCTT) during exercise. Blood was collected pre- and post exercise to determine gastrointestinal integrity biomarkers (i.e., I-FABP, sCD14, and CRP). Breath hydrogen (H2) and gastrointestinal symptoms (GIS) were determined pre-exercise, every 15 min, during and throughout recovery. No differences in gastrointestinal integrity biomarkers, OCTT, or distance completed were observed between trials. Pre-exercise total-GIS (1.3 ± 2.9 vs. 4.3 ± 4.4), gut discomfort (9.9 ± 8.1 vs. 15.8 ± 9.0), and upper-GIS (2.8 ± 2.6 vs. 5.7 ± 4.8) during exercise were less severe on high carbohydrate low FODMAP (HC-LFOD) versus high carbohydrate high FODMAP (HC-HFOD) (p < 0.05). Gut discomfort (3.4 ± 4.4 vs. 0.2 ± 0.6) and total-GIS (4.9 ± 6.8 vs. 0.2 ± 0.6) were higher during recovery on HC-LFOD versus HC-HFOD (p < 0.05). The FODMAP content of a 48 h high carbohydrate diet does not impact gastrointestinal integrity or motility in response to endurance exercise. However, a high FODMAP content exacerbates GIS before and during exercise, but this does not impact performance outcomes.

Gastrointestinal function following endurance exercise under different environmental temperatures.

PURPOSE: We determined the effects of different environmental temperatures on exercise-induced gastrointestinal (GI) damage and delayed gastric emptying (GE) rate. METHODS: Eleven trained males completed three trials on different days, consisting of (1) exercise in a thermoneutral environment (CON, 23 °C), (2) exercise in a hot environment (HOT, 35 °C), and (3) exercise in a cold environment (COLD, 10 °C). The subjects performed high-intensity interval-type endurance exercises in all trials. Blood intestinal fatty acid binding protein (I-FABP) levels was determine before and after exercise. We evaluated Tmax (time when the 13C-excretion/h reached a maximum level) as an indication of the GE rate during post-exercise. RESULTS: Rectal temperature during exercise was significantly higher (P < 0.001) in the HOT (38.7 ± 0.3 °C) trial compared with the CON (38.2 ± 0.3 °C) and COLD (38.2 ± 0.3 °C) trials, with no significant difference between the CON and COLD trials. Plasma I-FABP level after exercise (relative to the pre-exercise level) were significantly greater (P = 0.005) in the HOT trial (92.9 ± 69.6%) than in the CON (37.2 ± 31.6%) and COLD (37.6 ± 41.8%) trials. However, there was no significant difference between the CON and COLD trials. Moreover, the Tmax was delayed significantly (P = 0.006) in the HOT trial compared with the CON and COLD trials, with no significant difference between the CON and COLD trials. CONCLUSION: GI function following endurance exercise was similar between thermoneutral and cold environments, while endurance exercise in a hot environment exacerbated GI function compared with thermoneutral and cold environments.

Stretchable Device for Simultaneous Measurements of Contractility and Electrophysiology of Neuromuscular Tissue in the Gastrointestinal Tract.

Devices interfacing with biological tissues can provide valuable insights into function, disease, and metabolism through electrical and mechanical signals. However, certain neuromuscular tissues, like those in the gastrointestinal tract, undergo significant strains of up to 40%. Conventional inextensible devices cannot capture the dynamic responses in these tissues. This study introduces electrodes made from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and polydimethylsiloxane (PDMS) that enable simultaneous monitoring of electrical and mechanical responses of gut tissue. The soft PDMS layers conform to tissue surfaces during gastrointestinal movement. Dopants, including Capstone FS-30 and polyethylene glycol, are explored to enhance the conductivity, electrical sensitivity to strain, and stability of the PEDOT:PSS. The devices are fabricated using shadow masks and solution-processing techniques, providing a faster and simpler process than traditional clean-room-based lithography. Tested on ex vivo mouse colon and human stomach, the device recorded voltage changes of up to 300 µV during contraction and distension consistent with muscle activity, while simultaneously recording resistance changes of up to 150% due to mechanical strain. These devices detect and respond to chemical stimulants and blockers, and can induce contractions through electrical stimulation. They hold great potential for studying and treating complex disorders like irritable bowel syndrome and gastroparesis.

Mechanical experimentation of the gastrointestinal tract: a systematic review.

The gastrointestinal (GI) organs of the human body are responsible for transporting and extracting nutrients from food and drink, as well as excreting solid waste. Biomechanical experimentation of the GI organs provides insight into the mechanisms involved in their normal physiological functions, as well as understanding of how diseases can cause disruption to these. Additionally, experimental findings form the basis of all finite element (FE) modelling of these organs, which have a wide array of applications within medicine and engineering. This systematic review summarises the experimental studies that are currently in the literature (n = 247) and outlines the areas in which experimentation is lacking, highlighting what is still required in order to more fully understand the mechanical behaviour of the GI organs. These include (i) more human data, allowing for more accurate modelling for applications within medicine, (ii) an increase in time-dependent studies, and (iii) more sophisticated in vivo testing methods which allow for both the layer- and direction-dependent characterisation of the GI organs. The findings of this review can also be used to identify experimental data for the readers' own constitutive or FE modelling as the experimental studies have been grouped in terms of organ (oesophagus, stomach, small intestine, large intestine or rectum), test condition (ex vivo or in vivo), number of directions studied (isotropic or anisotropic), species family (human, porcine, feline etc.), tissue condition (intact wall or layer-dependent) and the type of test performed (biaxial tension, inflation-extension, distension (pressure-diameter), etc.). Furthermore, the studies that investigated the time-dependent (viscoelastic) behaviour of the tissues have been presented.

Active distance control in multi-capsule endoscopy via closed loop electromagnetic force between capsules.

Capsule endoscopy offers a non-invasive and patient-friendly method for imaging the gastrointestinal tract, boasting superior tissue accessibility compared to traditional endoscopy and colonoscopy. While advances have led to capsules capable of drug delivery, tactile sensing, and biopsy, size constraints often limit a single capsule from having multifunctionality. In response, we introduce multi-capsule endoscopy, where individually ingested capsules, each with unique functionalities, work collaboratively. However, synchronized navigation of these capsules is essential for this approach. In this paper, we present an active distance control strategy using a closed-loop system. This entails equipping one capsule with a sphere permanent magnet and the other with a solenoid. We utilized a Simulink model, incorporating (i) the peristalsis motion on the primary capsule, (ii) a PID controller, (iii) force dynamics between capsules through magnetic dipole approximation, and (iv) position tracking of the secondary capsule. For practical implementation, Hall effect sensors determined the inter-capsule distance, and a PID controller adjusted the solenoid's current to maintain the desired capsule spacing. Our proof-of-concept experiments, conducted on phantoms and ex vivo bovine tissues, pulled the leading capsule mimicking a typical human peristalsis speed of 1 cm/min. Results showcased an inter-capsule distance of 1.94 mm ± 0.097 mm for radii of curvature at 500 mm, 250 mm, and 100 mm, aiming for a 2-mm capsule spacing. For ex vivo bovine tissue, the achieved distance was 0.97 ± 0.28 mm against a target inter-capsule distance of 1 mm. Through the successful demonstration of precise inter-capsule control, this study paves the way for the potential of multi-capsule endoscopy in future research.

Energy-Efficient Ingestible Drug Delivery System in the Dynamic Gastrointestinal Environment.

Ingestible electronics are promising platforms for on-demand health monitoring and drug delivery. However, these devices and their actuators must operate in the gastrointestinal (GI) environment, which has a pH range of 1 to 8. Drug delivery systems using electrochemical dissolution of metal films are particularly susceptible to pH changes. Optimal operation in this dynamic environment stands to transform our capacity to help patients across a range of conditions. Here we present an energy-efficient ingestible electronic electrochemical drug delivery system to support subjects through operation in this dynamic environment. The proposed system consists of a drug reservoir sealed with an electrochemically dissolvable gold membrane and an electronic subsystem. An electronic subsystem controls the rate of gold dissolution by sensing and adapting to the pH of the GI environment and provides an option for energy-efficient drug delivery, reducing energy consumption by up to 42.8 %. Integrating the electronics with electrochemical drug delivery enables the proposed system to adapt to the dynamic physiological environments which makes it suitable for drug and/or therapeutic delivery at different locations in the GI tract.

Gut Isolation from Zebrafish Larvae for Single-cell RNA Sequencing.

The gastrointestinal (GI) tract performs a range of functions essential for life. Congenital defects affecting its development can lead to enteric neuromuscular disorders, highlighting the importance to understand the molecular mechanisms underlying GI development and dysfunction. In this study, we present a method for gut isolation from zebrafish larvae at 5 days post fertilization to obtain live, viable cells which can be used for single-cell RNA sequencing (scRNA-seq) analysis. This protocol is based on the manual dissection of the zebrafish intestine, followed by enzymatic dissociation with papain. Subsequently, cells are submitted to fluorescence-activated cell sorting, and viable cells are collected for scRNA-seq. With this method, we were able to successfully identify different intestinal cell types, including epithelial, stromal, blood, muscle, and immune cells, as well as enteric neurons and glia. Therefore, we consider it to be a valuable resource for studying the composition of the GI tract in health and disease, using the zebrafish.

Spatial Single-Cell Technologies for Exploring Gastrointestinal Tissue Transcriptome.

In the gastrointestinal (GI) system, like in other organ systems, the histological structure is a key determinant of physiological function. Tissues form multiple layers in the GI tract to perform their specialized functions in secretion, absorption, and motility. Even at the single layer, the heterogeneous cell population performs a diverse range of digestive or regulatory functions. Although many details of such functions at the histological and cell biological levels were revealed by traditional methods such as cell sorting, isolation, and culture, as well as histological methods such as immunostaining and RNA in situ hybridization, recent advances in spatial single-cell technologies could further contribute to our understanding of the molecular makeup of GI histological structures by providing a genome-wide overview of how different genes are expressed across individual cells and tissue layers. The current minireview summarizes recent advances in the spatial transcriptomics field and discusses how such technologies can promote our understanding of GI physiology. © 2023 American Physiological Society. Compr Physiol 13:4709-4718, 2023.

Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections.

Coronavirus disease 2019 (COVID-19) has been demonstrated to affect several systems of the human body, including the gastrointestinal and nervous systems. The enteric nervous system (ENS) is a division of the autonomic nervous system that extends throughout the gut, regulates gastrointestinal function, and is therefore involved in most gut dysfunctions, including those resulting from many viral infections. Growing evidence highlights enteric neural cells and microbiota as important players in gut inflammation and dysfunction. Furthermore, the ENS and gastrointestinal immune system work together establishing relevant neuroimmune interactions during both health and disease. In recent years, gut-driven processes have also been implicated as players in systemic inflammation and in the initiation and propagation of several central nervous system pathologies, which seem to be hallmarks of COVID-19. In this review, we aim to describe evidence of the gastrointestinal and ENS infection with a focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss here viral-induced mechanisms, neuroplasticity, and neuroinflammation to call attention to the enteric neuroglial network as a nervous system with a sensitive and crucial position to be not only a target of the new coronavirus but also a way in and trigger of COVID-19-related symptoms.

Static in vitro digestion model adapted to the general older adult population: an INFOGEST international consensus.

Understanding the mechanisms of food digestion is of paramount importance to determine the effect foods have on human health. Significant knowledge on the fate of food during digestion has been generated in healthy adults due to the development of physiologically-relevant in vitro digestion models. However, it appears that the performance of the oro-gastrointestinal tract is affected by ageing and that a model simulating the digestive conditions found in a younger adult (<65 years) is not relevant for an older adult (>65 years). The objectives of the present paper were: (1) to conduct an exhaustive literature search to find data on the physiological parameters of the older adult oro-gastrointestinal tract, (2) to define the parameters of an in vitro digestion model adapted to the older adult. International experts have discussed all the parameters during a dedicated workshop organized within the INFOGEST network. Data on food bolus properties collected in the older adult were gathered, including food particle size found in older adult boluses. In the stomach and small intestine, data suggest that significant physiological changes are observed between younger and older adults. In the latter, the rate of gastric emptying is slowed down, the pH of the stomach content is higher, the amount of secretions and thus the hydrolytic activities of gastric and intestinal digestive enzymes are reduced and the concentration of bile salts lower. The consensus in vitro digestion model of the older adult proposed here will allow significant progress to be made in understanding the fate of food in this specific population, facilitating the development of foods adapted to their nutritional needs. Nevertheless, better foundational data when available and further refinement of the parameters will be needed to implement the proposed model in the future.

Motilin is a regulator of gastric contraction in Japanese fire belly newts (Cynops pyrrhogaster), in vitro studies using isolated gastrointestinal strips of newts, rabbits, and chickens.

The effects of newt motilin on the contractility of the isolated gastrointestinal (GI) tract from Japanese fire belly newts (newt) were examined to clarify whether motilin regulates GI motility in urodele amphibians. In addition, contractile responsiveness to motilins from seven species of vertebrates (human, chicken, turtle, alligator, axolotol, newt and zebrafish) were compared in GI preparations from three different animals (rabbit duodenum, chicken ileum and newt stomach) to determine the species-specific action of motilin. Newt motilin (10-10 M - 10-6 M) caused a contraction of cognate gastric strips, while the upper, middle, and lower intestinal strips were insensitive. The rank order of motilins for contractile activity in newt gastric strips was newt > alligator > axolotol > chicken > turtle > human ≫ zebrafish. On the other hand, newt motilin caused a weak contraction in the rabbit duodenum (human > alligator = chicken > turtle > newt ≧ axolotol > zebrafish), and it was ineffective in the chicken ileum (chicken > turtle > alligator > human ≫ newt, axolotol and zebrafish). This study demonstrates that motilin induces contraction in the GI tract of a urodele amphibian, the newt, in a region (stomach)-specific manner and further indicates that a ligand-receptor interaction of the motilin system is a species-specific manner probably due to differences in the amino acid sequence of motilin.

Key Stress Response Mechanisms of Probiotics During Their Journey Through the Digestive System: A Review.

The survival of probiotic microorganisms during their exposure to harsh environments plays a critical role in the fulfillment of their functional properties. In particular, transit through the human gastrointestinal tract (GIT) is considered one of the most challenging habitats that probiotics must endure, because of the particularly stressful conditions (e.g., oxygen level, pH variations, nutrient limitations, high osmolarity, oxidation, peristalsis) prevailing in the different sections of the GIT, which in turn can affect the growth, viability, physiological status, and functionality of microbial cells. Consequently, probiotics have developed a series of strategies, called "mechanisms of stress response," to protect themselves from these adverse conditions. Such mechanisms may include but are not limited to the induction of new metabolic pathways, formation/production of particular metabolites, and changes of transcription rates. It should be highlighted that some of such mechanisms can be conserved across several different strains or can be unique for specific genera. Hence, this review attempts to review the state-of-the-art knowledge of mechanisms of stress response displayed by potential probiotic strains during their transit through the GIT. In addition, evidence whether stress responses can compromise the biosafety of such strains is also discussed.

Normal gastrointestinal temperature values measured through ingestible capsules technology: a systematic review.

Climate change has amplified the importance of continuous and precise body core temperature (Tcore) monitoring in the everyday life. In this context, assessing Tcore through ingestible capsules technology, i.e., gastrointestinal temperature (Tgastrointestinal), emerges as a good alternative to prevent heat-related illness. Therefore, we conducted a systematic review to point out values of normal Tgastrointestinal measured through ingestible capsules in healthy humans. The study followed PRISMA guidelines and searched the PubMed and Scielo databases from 1971 to 2023. Our search strategy included the descriptors ("gastrointestinal temperature") AND ("measurement"), and eligible studies had to be written in English and measured Tgastrointestinal using ingestible capsules or sensors in healthy adults aged 18-59 at rest. Two pairs of researchers independently reviewed titles and abstracts and identified 35 relevant articles out of 1,088 in the initial search. An average value of 37.13 °C with a standard deviation of 0.24 °C was observed, independently of the gender. The values measured ranged from 36.70 °C to 37.69 °C. In conclusion, this systematic review pointed out the mean value of 37.13 ± 0.24 °C measured by ingestible capsules as reference for resting Tgastrointestinal in healthy adult individuals.

Ca2+ Signaling Is the Basis for Pacemaker Activity and Neurotransduction in Interstitial Cells of the GI Tract.

Years ago gastrointestinal motility was thought to be due to interactions between enteric nerves and smooth muscle cells (SMCs) in the tunica muscularis. Thus, regulatory mechanisms controlling motility were either myogenic or neurogenic. Now we know that populations of interstitial cells, c-Kit+ (interstitial cells of Cajal or ICC), and PDGFRα+ cells (formerly "fibroblast-like" cells) are electrically coupled to SMCs, forming the SIP syncytium. Pacemaker and neurotransduction functions are provided by interstitial cells through Ca2+ release from the endoplasmic reticulum (ER) and activation of Ca2+-activated ion channels in the plasma membrane (PM). ICC express Ca2+-activated Cl- channels encoded by Ano1. When activated, Ano1 channels produce inward current and, therefore, depolarizing or excitatory effects in the SIP syncytium. PDGFRα+ cells express Ca2+-activated K+ channels encoded by Kcnn3. These channels generate outward current when activated and hyperpolarizing or membrane-stabilizing effects in the SIP syncytium. Inputs from enteric and sympathetic neurons regulate Ca2+ transients in ICC and PDGFRα+ cells, and currents activated in these cells conduct to SMCs and regulate contractile behaviors. ICC also serve as pacemakers, generating slow waves that are the electrophysiological basis for gastric peristalsis and intestinal segmentation. Pacemaker types of ICC express voltage-dependent Ca2+ conductances that organize Ca2+ transients, and therefore Ano1 channel openings, into clusters that define the amplitude and duration of slow waves. Ca2+ handling mechanisms are at the heart of interstitial cell function, yet little is known about what happens to Ca2+ dynamics in these cells in GI motility disorders.

[Recent topics on interorgan communication networks and gut microbiota].

The living body is composed of diverse organ systems, each of which has its own characteristic control mechanisms and complex in vivo responses. Between the brain and organs such as the heart, kidney, liver, pancreas, gastrointestinal tract, and even muscles, there is a sophisticated and complex regulatory system. Coordinated interactions through communication between organs are essential for maintaining health. In this review, we introduce four research trends in inter-organ networks, with a focus on the digestive system: 1) Inter-organ networks on metabolic systems, 2) Inter-organ networks originating from the gastrointestinal tract, 3) Intestinal bacteria, that is one of the biggest topics in recent years, 4) Research results on the involvement of gut microbiota in the inter-organ network between the kidney and the gastrointestinal tract. An integrated understanding and investigation of the regulatory mechanisms of inter-organ communication networks are expected to extend healthy life span and improve quality of life.

A tissue-like neurotransmitter sensor for the brain and gut.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. 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.