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Communications Biology Dec 2023Assessing gastrointestinal motility lacks simultaneous evaluation of intraluminal pressure (ILP), circular muscle (CM) and longitudinal muscle (LM) contraction, and...
Assessing gastrointestinal motility lacks simultaneous evaluation of intraluminal pressure (ILP), circular muscle (CM) and longitudinal muscle (LM) contraction, and lumen emptying. In this study, a sophisticated machine was developed that synchronized real-time recordings to quantify the intricate interplay between CM and LM contractions, and their timings for volume changes using high-resolution cameras with machine learning capability, the ILP using pressure transducers and droplet discharge (DD) using droplet counters. Results revealed four distinct phases, B, N, D, and A, distinguished by pressure wave amplitudes. Fluid filling impacted LM strength and contraction frequency initially, followed by CM contraction affecting ILP, volume, and the extent of anterograde, retrograde, and segmental contractions during these phases that result in short or long duration DD. This comprehensive analysis sheds light on peristalsis mechanisms, understand their sequence and how one parameter influenced the other, offering insights for managing peristalsis by regulating smooth muscle contractions.
Topics: Animals; Mice; Peristalsis; Gastrointestinal Motility; Muscle Contraction; Intestine, Small
PubMed: 38062160
DOI: 10.1038/s42003-023-05631-2 -
Virology Journal Nov 2023Gastrointestinal motility refers to the peristalsis and contractility of gastrointestinal muscles, including the force and frequency of gastrointestinal muscle... (Review)
Review
Gastrointestinal motility refers to the peristalsis and contractility of gastrointestinal muscles, including the force and frequency of gastrointestinal muscle contraction. Gastrointestinal motility maintains the normal digestive function of the human body and is a critical component of the physiological function of the digestive tract. At present, gastrointestinal motility disorder-related diseases are gradually affecting human production and life. In recent years, it has been consistently reported that the enteric nervous system has a coordinating and controlling role in gastrointestinal motility. Motility disorders are closely related to functional or anatomical changes in the gastrointestinal nervous system. At the same time, some viral infections, such as herpes simplex virus and varicella-zoster virus infections, can cause damage to the gastrointestinal nervous system. Therefore, this paper describes the mechanisms of viral infection in the gastrointestinal nervous system and the associated clinical manifestations. Studies have indicated that the means by which viruses can cause the infection of the enteric nervous system are various, including retrograde transport, hematogenous transmission and centrifugal transmission from the central nervous system. When viruses infect the enteric nervous system, they can cause clinical symptoms, such as abdominal pain, abdominal distension, early satiation, belching, diarrhea, and constipation, by recruiting macrophages, lymphocytes and neutrophils and regulating intestinal microbes. The findings of several case‒control studies suggest that viruses are the cause of some gastrointestinal motility disorders. It is concluded that one of the causes of gastrointestinal motility disorders is viral infection of the enteric nervous system. In such disorders, the relationships between viruses and nerves remain to be studied more deeply. Further studies are necessary to evaluate whether prophylactic antiviral therapy is feasible in gastrointestinal motility disorders.
Topics: Humans; Gastrointestinal Tract; Enteric Nervous System; Constipation; Herpes Zoster; Gastrointestinal Motility; Gastrointestinal Diseases
PubMed: 37915051
DOI: 10.1186/s12985-023-02185-x -
Biological & Pharmaceutical Bulletin 2024Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few...
Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.
Topics: Humans; Animals; Irritable Bowel Syndrome; Peristalsis; Prospective Studies; Models, Animal; Diarrhea; Chalcones
PubMed: 38325854
DOI: 10.1248/bpb.b23-00680 -
Materials Today. Bio Jun 2024As a booming engineering technology, the microfluidic chip has been widely applied for replicating the complexity of human intestinal micro-physiological ecosystems .... (Review)
Review
As a booming engineering technology, the microfluidic chip has been widely applied for replicating the complexity of human intestinal micro-physiological ecosystems . Biosensors, 3D imaging, and multi-omics have been applied to engineer more sophisticated intestinal barrier-on-chip platforms, allowing the improved monitoring of physiological processes and enhancing chip performance. In this review, we report cutting-edge advances in the microfluidic techniques applied for the establishment and evaluation of intestinal barrier platforms. We discuss different design principles and microfabrication strategies for the establishment of microfluidic gut barrier models . Further, we comprehensively cover the complex cell types (e.g., epithelium, intestinal organoids, endothelium, microbes, and immune cells) and controllable extracellular microenvironment parameters (e.g., oxygen gradient, peristalsis, bioflow, and gut-organ axis) used to recapitulate the main structural and functional complexity of gut barriers. We also present the current multidisciplinary technologies and indicators used for evaluating the morphological structure and barrier integrity of established gut barrier models . Finally, we highlight the challenges and future perspectives for accelerating the broader applications of these platforms in disease simulation, drug development, and personalized medicine. Hence, this review provides a comprehensive guide for the development and evaluation of microfluidic-based gut barrier platforms.
PubMed: 38774450
DOI: 10.1016/j.mtbio.2024.101079 -
Frontiers in Pediatrics 2023Assessment of bowel health in ill preterm infants is essential to prevent and diagnose early potentially life-threatening intestinal conditions such as necrotizing...
INTRODUCTION
Assessment of bowel health in ill preterm infants is essential to prevent and diagnose early potentially life-threatening intestinal conditions such as necrotizing enterocolitis. Auscultation of bowel sounds helps assess peristalsis and is an essential component of this assessment.
AIM
We aim to compare conventional bowel sound auscultation using acoustic recordings from an electronic stethoscope to real-time bowel motility visualized on point-of-care bowel ultrasound (US) in neonates with no known bowel disease.
METHODS
This is a prospective observational cohort study in neonates on full enteral feeds with no known bowel disease. A 3M™ Littmann® Model 3200 electronic stethoscope was used to obtain a continuous 60-s recording of bowel sounds at a set region over the abdomen, with a concurrent recording of US using a 12l high-frequency Linear probe. The bowel sounds heard by the first investigator using the stethoscope were contemporaneously transferred for a computerized assessment of their electronic waveforms. The second investigator, blinded to the auscultation findings, obtained bowel US images using a 12l Linear US probe. All recordings were analyzed for bowel peristalsis (duration in seconds) by each of the two methods.
RESULTS
We recruited 30 neonates (gestational age range 27-43 weeks) on full enteral feeds with no known bowel disease. The detection of bowel peristalsis (duration in seconds) by both methods (acoustic and US) was reported as a percentage of the total recording time for each participant. Comparing the time segments of bowel sound detection by digital stethoscope recording to that of the visual detection of bowel movements in US revealed a median time of peristalsis with US of 58%, compared to 88.3% with acoustic assessment ( < 0.002). The median regression difference was 26.7% [95% confidence interval (CI) 5%-48%], demonstrating no correlation between the two methods.
CONCLUSION
Our study demonstrates disconcordance between the detection of bowel sounds by auscultation and the detection of bowel motility in real time using US in neonates on full enteral feeds and with no known bowel disease. Better innovative methods using artificial intelligence to characterize bowel sounds, integrating acoustic mapping with sonographic detection of bowel peristalsis, will allow us to develop continuous neonatal bowel sound monitoring devices.
PubMed: 37794960
DOI: 10.3389/fped.2023.1173332 -
Nutrients Oct 2023Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate...
Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate gut motility, especially through the tryptophan metabolism pathway. However, the role of indoles as microbial tryptophan metabolites in colonic function requires further exploration. Here, we show that the delivery of indole acetic acid (IAA) targeting the colon can improve gut motility by activating the aryl hydrocarbon receptor (AHR). To achieve colon-targeted delivery, Eudragit S-100 (ES) and chitosan (CS) were used as drug carriers. After optimisation, IAA-loaded ES-coated CS nanoparticles exhibited an encapsulation efficiency of 83% and a drug-loading capacity of 16%. These nanoparticles exhibited pH-dependent characteristics and remained stable in acidic conditions and the upper intestine. In simulated intestinal fluid (pH 7.4) and colonic lumen, considerable amounts of IAA were released after approximately 4 h. Compared with free IAA, the nanoparticles exerted enhanced therapeutic effects on gut movement disorders induced by loperamide. The efficacy of IAA treatment was attributable to the activation of the AHR signalling pathway and increased levels of AHR agonists. Furthermore, the oral administration of IAA-loaded nanoparticles promoted serotonin secretion and maintained the intestinal barrier function. The experimental outcomes demonstrate the efficiency of the proposed colon-specific delivery system and highlight the role of IAA, produced by gut microbiota metabolism, in regulating gut peristalsis through AHR activation.
Topics: Receptors, Aryl Hydrocarbon; Tryptophan; Colon; Signal Transduction
PubMed: 37836566
DOI: 10.3390/nu15194282 -
Scientific Reports May 2024Ticks are blood-feeding arthropods that require heme for their successful reproduction. During feeding they also acquire pathogens that are subsequently transmitted to...
Ticks are blood-feeding arthropods that require heme for their successful reproduction. During feeding they also acquire pathogens that are subsequently transmitted to humans, wildlife and/or livestock. Understanding the regulation of tick midgut is important for blood meal digestion, heme and nutrient absorption processes and for aspects of pathogen biology in the host. We previously demonstrated the activity of tick kinins on the cognate G protein-coupled receptor. Herein we uncovered the physiological role of the kinin receptor in the tick midgut. A fluorescently-labeled kinin peptide with the endogenous kinin 8 sequence (TMR-RK8), identical in the ticks Rhipicephalus microplus and R. sanguineus, activated and labeled the recombinant R. microplus receptor expressed in CHO-K1 cells. When applied to the live midgut the TMR-RK8 labeled the kinin receptor in muscles while the labeled peptide with the scrambled-sequence of kinin 8 (TMR-Scrambled) did not. The unlabeled kinin 8 peptide competed TMR-RK8, decreasing confocal microscopy signal intensity, indicating TMR-RK8 specificity to muscles. TMR-RK8 was active, inducing significant midgut peristalsis that was video-recorded and evaluated with video tracking software. The TMR-Scrambled peptide used as a negative control did not elicit peristalsis. The myotropic function of kinins in eliciting tick midgut peristalsis was established.
Topics: Animals; Kinins; CHO Cells; Peristalsis; Cricetulus; Neuropeptides; Muscles; Ticks; Rhipicephalus; Arthropod Proteins
PubMed: 38740831
DOI: 10.1038/s41598-024-61570-w -
BioRxiv : the Preprint Server For... Sep 2023Three-dimensional (3D) in vitro models are essential in cancer research, but they often neglect physical forces. In our study, we combined patient-derived tumor...
Three-dimensional (3D) in vitro models are essential in cancer research, but they often neglect physical forces. In our study, we combined patient-derived tumor organoids with a microfluidic organ-on-chip system to investigate colorectal cancer (CRC) invasion in the tumor microenvironment (TME). This allowed us to create patient-specific tumor models and assess the impact of physical forces on cancer biology. Our findings showed that the organoid-on-chip models more closely resembled patient tumors at the transcriptional level, surpassing organoids alone. Using 'omics' methods and live-cell imaging, we observed heightened responsiveness of KRAS mutant tumors to TME mechanical forces. These tumors also utilized the γ-aminobutyric acid (GABA) neurotransmitter as an energy source, increasing their invasiveness. This bioengineered model holds promise for advancing our understanding of cancer progression and improving CRC treatments.
PubMed: 37745376
DOI: 10.1101/2023.09.14.557797 -
Annals of Gastroenterology 2024Absent contractility (AC), a motility disorder characterized by the absence of esophageal contractions while maintaining normal lower esophageal sphincter relaxation, is... (Review)
Review
Absent contractility (AC), a motility disorder characterized by the absence of esophageal contractions while maintaining normal lower esophageal sphincter relaxation, is recognized as a distinctive major disorder of peristalsis on esophageal high-resolution manometry that warrants comprehensive understanding. This unique motility disorder often co-occurs with connective tissue, rheumatologic or autoimmune diseases, with scleroderma being the classic example. Symptoms of gastroesophageal reflux are common. AC can profoundly impact patients' lives and result in a spectrum of complications, including erosive esophagitis, esophageal candidiasis, Barrett's esophagus, and malnutrition. To address the intricate complexities of AC and its multifaceted complications, a multidisciplinary approach is paramount. This approach considers the distinct clinical presentation and underlying rheumatologic conditions of the individual patient, recognizing the inherent diversity within this disorder. While medical management of gastroesophageal reflux remains the cornerstone of AC treatment, emerging surgical and endoscopic interventions offer additional therapeutic options for those grappling with this challenging condition. This comprehensive review provides an in-depth evaluation of recent advances in our understanding of AC and its management. It endeavors to offer valuable insights into therapeutic strategies for AC and its associated issues.
PubMed: 38481777
DOI: 10.20524/aog.2024.0860 -
BioRxiv : the Preprint Server For... Oct 2023Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infants' intestinal tract that is exacerbated by significant difficulties in early and...
BACKGROUND
Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infants' intestinal tract that is exacerbated by significant difficulties in early and accurate diagnosis. In NEC disease, the intestine often exhibits hypoperfusion and dysmotility, which contributes to advanced disease pathogenesis. However, these physiological features cannot be accurately and quantitively assessed within the current constraints of imaging modalities frequently used in the clinic (plain film X-ray and ultrasound). We have previously demonstrated the ability of photoacoustic imaging (PAI) to non-invasively and quantitively assess intestinal tissue oxygenation and motility in a healthy neonatal rat model. As a first-in-disease application, we evaluated NEC pathogenesis using PAI to assess intestinal health biomarkers in a preclinical neonatal rat experimental model of NEC.
METHODS
NEC was induced in neonatal rat pups from birth to 4 days old via hypertonic formula feeding, full-body hypoxic stress, and lipopolysaccharide administration to mimic bacterial colonization. Healthy breastfed (BF) controls and NEC rat pups were imaged at 2- and 4-days old. Intestinal tissue oxygen saturation was measured with PAI imaging for oxy- and deoxyhemoglobin levels. To measure intestinal motility, ultrasound and co-registered PAI cine recordings were used to capture intestinal peristalsis motion and contrast agent (indocyanine green) transit within the intestinal lumen. Additionally, both midplane two-dimensional and volumetric three-dimensional imaging acquisitions were assessed for oxygenation and motility.
RESULTS
NEC pups showed a significant decrease of intestinal tissue oxygenation as compared to healthy BF controls at both ages (2-days old: 55.90% +/- 3.77% vs 44.12% +/- 7.18%; 4-days old: 56.13% +/- 3.52% vs 38.86% +/- 8.33%). Intestinal motility, assessed using a computational intestinal deformation analysis, demonstrated a significant reduction in the intestinal motility index in both early (2-day) and established (4-day) NEC. Extensive NEC damage was confirmed with histology and dysmotility was confirmed by small intestinal transit assay.
CONCLUSIONS
This study presents PAI as a successful emerging diagnostic imaging modality for both intestinal tissue oxygenation and intestinal motility disease hallmarks in a rat NEC model. PAI presents enormous significance and potential for fundamentally changing current clinical paradigms for detecting and monitoring intestinal pathologies in the premature infant.
PubMed: 37961632
DOI: 10.1101/2023.10.20.563296