-
BioRxiv : the Preprint Server For... Nov 2023Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into...
Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later - or not at all - showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.
PubMed: 38014241
DOI: 10.1101/2023.11.08.566304 -
Abdominal Radiology (New York) Sep 2023For the last 40 years, the ileal pouch-anal anastomosis has been used in patients with ulcerative colitis, familial adenomatous polyposis, and occasionally severe... (Review)
Review
For the last 40 years, the ileal pouch-anal anastomosis has been used in patients with ulcerative colitis, familial adenomatous polyposis, and occasionally severe constipation to reconstruct the gastrointestinal tract after proctocolectomy. Although the procedure has generally been successful in helping patients avoid an ileostomy, it has come with its own set of problems. These include complications of the surgery such as fistulas and bowel obstruction, persistent inflammation of the pouch known as pouchitis, and functional problems related to the lack of expulsive peristalsis in the pouch. It is this last group of problems that is exacerbated by a poor diet, ill-advised anti-diarrheal medications, anal stenosis and pouch twists. As a consequence, patients with pouch problems are frequently referred for radiologic evaluation, with pouchography, defecation studies, and small bowel imaging commonly requested. In this review, the basic anatomy and physiology of the ileal pouch are discussed to provide a logical baseline against which to measure the anatomy of pouches and its relationship to the symptoms of pouch dysfunction.
Topics: Humans; Proctocolectomy, Restorative; Colonic Pouches; Colitis, Ulcerative; Adenomatous Polyposis Coli; Pouchitis; Treatment Outcome
PubMed: 36853391
DOI: 10.1007/s00261-022-03721-z -
Cellular and Molecular Bioengineering Aug 2023In the colorectal cancer (CRC) tumor microenvironment, cancerous and precancerous cells continuously experience mechanical forces associated with peristalsis. Given that...
INTRODUCTION
In the colorectal cancer (CRC) tumor microenvironment, cancerous and precancerous cells continuously experience mechanical forces associated with peristalsis. Given that mechanical forces like shear stress and strain can positively impact cancer progression, we explored the hypothesis that peristalsis may also contribute to malignant progression in CRC. We defined malignant progression as enrichment of cancer stem cells and the acquisition of invasive behaviors, both vital to CRC progression.
METHODS
We leveraged our peristalsis bioreactor to expose CRC cell lines (HCT116), patient-derived xenograft (PDX1,2) lines, or non-cancerous intestinal cells (HIEC-6) to forces associated with peristalsis in vitro. Cells were maintained in static control conditions or exposed to peristalsis for 24 h prior to assessment of cancer stem cell (CSC) emergence or the acquisition of invasive phenotypes.
RESULTS
Exposure of HCT116 cells to peristalsis significantly increased the emergence of LGR5 CSCs by 1.8-fold compared to static controls. Peristalsis enriched LGR5 positivity in several CRC cell lines, notably significant in mutant lines. In contrast, peristalsis failed to increase LGR5 in non-cancerous intestinal cells, HIEC-6. LGR5 emergence downstream of peristalsis was dependent on ROCK and Wnt activity, and not YAP1 activation. Additionally, HCT116 cells adopted invasive morphologies when exposed to peristalsis, with increased filopodia density and epithelial to mesenchymal gene expression, in a Wnt dependent manner.
CONCLUSIONS
Peristalsis associated forces drive malignant progression of CRC via ROCK, YAP1, and Wnt-related mechanotransduction.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12195-023-00776-w.
PubMed: 37811008
DOI: 10.1007/s12195-023-00776-w -
Medical & Biological Engineering &... Aug 2023Ureteral obstruction is a urinary system disease that causes urinary retention, renal injury, renal colic, and infection. Ureteral stents are often used for conservative...
BACKGROUND
Ureteral obstruction is a urinary system disease that causes urinary retention, renal injury, renal colic, and infection. Ureteral stents are often used for conservative treatment in clinics, and their migration usually results in ureteral stent failure. The migrations include proximal migration to the kidney side and distal migration to the bladder side, but the biomechanism of stent migration is still unknown.
METHOD
Finite element models of stents with lengths from 6-30 cm were developed. The stents were implanted into the middle of the ureter to analyze the effect of stent length on its migration, and the effect of stent implantation position on 6-cm-long stent migration was also observed. The stents' maximum axial displacement was used to assess the ease of stent migration. A time-varying pressure was applied to the ureter outer wall to simulate peristalsis. The stent and ureter adopted friction contact conditions. The two ends of the ureter were fixed. The radial displacement of the ureter was used to evaluate the effect of the stent on peristalsis.
RESULTS AND DISCUSSION
The maximum migration occurs in the positive direction for a 6-cm-long stent implanted at the proximal ureter (CD and DE), but in the negative direction at the distal ureter (FG and GH). The 6-cm-long stent demonstrated almost no effect on ureteral peristalsis. The 12-cm-long stent diminished the radial displacement of the ureter from 3-5 s. The 18-cm stent diminished the radial displacement of the ureter from 0-8 s, and the radial displacement within 2-6 s was weaker than other time. The 24-cm stent diminished the radial displacement of the ureter from 0-8 s, and the radial displacement within 1-7 s was weaker than other time.
CONCLUSION
The biomechanism of stent migration and ureteral peristalsis weakening after stent implantation was explored. Shorter stents were more likely to migrate. The implantation position had less influence on ureteral peristalsis compared with the stent length, which provided a reference for stent design aimed at reducing stent migration. Stent length was the main factor affecting ureteral peristalsis. This study provides a reference for the study of ureteral peristalsis.
Topics: Ureter; Urinary Bladder; Kidney; Stents
PubMed: 37322393
DOI: 10.1007/s11517-023-02856-5 -
Physiological Reviews Jan 2024The gastrointestinal (GI) tract displays multiple motor patterns that move nutrients and wastes through the body. Smooth muscle cells (SMCs) provide the forces necessary... (Review)
Review
The gastrointestinal (GI) tract displays multiple motor patterns that move nutrients and wastes through the body. Smooth muscle cells (SMCs) provide the forces necessary for GI motility, but interstitial cells, electrically coupled to SMCs, tune SMC excitability, transduce inputs from enteric motor neurons, and generate pacemaker activity that underlies major motor patterns, such as peristalsis and segmentation. The interstitial cells regulating SMCs are interstitial cells of Cajal (ICC) and PDGF receptor (PDGFR)α cells. Together these cells form the SIP syncytium. ICC and PDGFRα cells express signature Ca-dependent conductances: ICC express Ca-activated Cl channels, encoded by , that generate inward current, and PDGFRα cells express Ca-activated K channels, encoded by , that generate outward current. The open probabilities of interstitial cell conductances are controlled by Ca release from the endoplasmic reticulum. The resulting Ca transients occur spontaneously in a stochastic manner. Ca transients in ICC induce spontaneous transient inward currents and spontaneous transient depolarizations (STDs). Neurotransmission increases or decreases Ca transients, and the resulting depolarizing or hyperpolarizing responses conduct to other cells in the SIP syncytium. In pacemaker ICC, STDs activate voltage-dependent Ca influx, which initiates a cluster of Ca transients and sustains activation of ANO1 channels and depolarization during slow waves. Regulation of GI motility has traditionally been described as neurogenic and myogenic. Recent advances in understanding Ca handling mechanisms in interstitial cells and how these mechanisms influence motor patterns of the GI tract suggest that the term "myogenic" should be replaced by the term "SIPgenic," as this review discusses.
Topics: Humans; Interstitial Cells of Cajal; Receptor, Platelet-Derived Growth Factor alpha; Muscle, Smooth; Gastrointestinal Tract; Intestine, Small
PubMed: 37561138
DOI: 10.1152/physrev.00036.2022 -
Fertility and Sterility May 2024To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle... (Observational Study)
Observational Study
OBJECTIVE
To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle tracking method.
DESIGN
A multicenter prospective observational study took place in three European centers between 2014 and 2023.
SETTING
One university teaching hospital, 1 teaching hospital and 1 specialised clinic.
PATIENTS
A total of 46 women with a sonographic or magnetic resonance imaging diagnosis of adenomyosis were included. 106 healthy controls without uterine pathologies were included.
INTERVENTION
Four-minute TVUS recordings were performed and four uterine contractility features were extracted using a speckle tracking algorithm.
MAIN OUTCOMES MEASURES
The extracted features were contraction frequency (contractions/min), amplitude, velocity (mm/s), and coordination. Women with adenomyosis were compared with healthy controls according to the phase of the menstrual cycle.
RESULTS
Throughout the different phases of the menstrual cycle, trends of increased amplitude, decreased frequency and velocity, and reduced contraction coordination were seen in patients with adenomyosis compared with healthy controls. These were statistically significant in the late follicular phase, with a higher amplitude (0.087 ± 0.042 vs. 0.050 ± 0.018), lower frequency and velocity (1.49 ± 0.22 vs. 1.68 ± 0.25 contractions/min, and 0.65 ± 0.18 vs. 0.88 ± 0.29 mm/s, respectively), and reduced contraction coordination (0.34 ± 0.08 vs. 0.26 ± 0.17), in the late luteal phase, with higher amplitude (0.050 ± 0.022 vs. 0.035 ± 0.013), lower velocity (0.51 ± 0.11 vs. 0.65 ± 0.13 mm/s), and reduced contraction coordination (0.027 ± 0.06 vs. 0.18 ± 0.07), and in the midfollicular phase, with decreased frequency (1.48 ± 0.21 vs. 1.69 ± 0.16 contractions/min) in patients with adenomyosis compared with healthy controls. During menses, a higher pain score was significantly associated with lower frequency and velocity and higher contraction amplitude. Results remained significant after correcting for age, parity, and body mass index.
CONCLUSION
Uterine contractility differs in patients with adenomyosis compared with healthy controls throughout the phases of the menstrual cycle. This suggests an etiologic mechanism for the infertility and dysmenorrhea seen in patients with adenomyosis. Moreover, it presents new potential therapeutic targets and diagnostic markers.
Topics: Humans; Female; Adenomyosis; Uterine Contraction; Adult; Prospective Studies; Uterus; Ultrasonography; Case-Control Studies; Middle Aged; Menstrual Cycle; Predictive Value of Tests
PubMed: 38199285
DOI: 10.1016/j.fertnstert.2024.01.009 -
Critical Reviews in Food Science and... Dec 2023Bioengineered strategies enable gut chips to faithfully replicate essential features of intestinal microsystems, encompassing geometric properties, peristalsis,... (Review)
Review
Bioengineered strategies enable gut chips to faithfully replicate essential features of intestinal microsystems, encompassing geometric properties, peristalsis, intraluminal fluid flow, oxygen gradients, and the microbiome. This emerging technique serves as a powerful tool for nutrition studies by emulating the absorption and distribution processes in a manner highly relevant to human physiology. It offers unprecedented accessibility for investigating the mechanisms governing nutrition metabolism. While the application of gut-on-chip models in disease modeling and drug screening has been extensively explored, their potential in dietary nutrition research remains relatively unexplored. This comprehensive review provides an overview of the different approaches employed in constructing gut-on-chip platforms using diverse cell sources and niche mimics. Furthermore, it explores the applications and prospects of gut-on-chips in nutrition-related investigations, with a specific focus on carotenoid transport, absorption, and metabolism. Lastly, this review discusses the future development trajectory of this groundbreaking technology paradigm, highlighting its broad applicability in the field of food technology. By harnessing the capabilities of these state-of-the-art techniques within gut chip platforms, researchers can establish a robust scientific foundation for unraveling the intricate mechanisms that govern the behavior and functional properties of carotenoids.
PubMed: 38095598
DOI: 10.1080/10408398.2023.2293250 -
Journal of Ethnopharmacology Oct 2023San Hua Tang (SHT) was first mentioned in the book "The Collection of Plain Questions about Pathogenesis, Qi, and Life." SHT has the effect of dispelling wind and...
Application of omics technology to investigate the mechanism underlying the role of San Hua Tang in regulating microglia polarization and blood-brain barrier protection following ischemic stroke.
ETHNOPHARMACOLOGY RELEVANCE
San Hua Tang (SHT) was first mentioned in the book "The Collection of Plain Questions about Pathogenesis, Qi, and Life." SHT has the effect of dispelling wind and dredging collaterals, dredging viscera, and guiding stagnation, and is used in the treatment of ischemic stroke (IS). SHT is composed of Rheum palmatum L., Magnolia officinalis Rehder & E.H.Wilson, Citrus assamensis S.Dutta & S.C.Bhattacharya, and Notopterygium tenuifolium M.L.Sheh & F.T.Pu, which is the traditional prescription of the Tongxia method for the treatment of stroke. Tongxia is one of the "eight methods" used in traditional Chinese medicine, which plays a role in treating diseases by promoting gastrointestinal peristalsis and defecation. Studies have demonstrated a close relationship between gut microbiota metabolism and cerebral stroke; however, the role of SHT in IS treatment through gut microbiota or intestinal metabolites is unclear.
AIM OF THE STUDY
To explore the connotation of the Xuanfu theory and clarify the mechanism underlying SHT-mediated opening Xuanfu methods. Through metabolomics, 16S rRNA gene sequencing, and molecular biology techniques, research on the changes in the gut microbiota and blood-brain barrier (BBB) will highlight greater strategies for the treatment of stroke.
MATERIALS AND METHODS
We used pseudo-germ-free (PGF) rats combined with an ischemia/reperfusion (I/R) rat model for the follow-up experimental research. PGF rats were prepared by the intragastric administration of an antibiotic cocktail for 6 days, following which SHT was administered for 5 consecutive days. The I/R model was performed 1 day following the concluding administration of SHT. We detected the neurological deficit score, cerebral infarct volume, serum inflammatory factor levels (interleukin IL-6, IL-10, IL-17, and tumor necrosis factor alpha), tight junction-related proteins (Zonula occludens-1, Occludin, and Claudin-5), and small glue plasma cell-associated proteins (Cluster of Differentiation 16/Cluster of Differentiation 206, Matrix metalloproteinase, ionized calcium-binding adapter molecule 1, and C-X3-C Motif Chemokine Ligand 1) 24 h following I/R. Using 16S rRNA gene sequencing and non-targeted metabolomics analysis, we explored the relationship between fecal microecology and serum metabolites. Eventually, we analyzed the correlation between the gut microbiota and plasma metabolic profile as well as the mechanism underlying the SHT-mediated regulation of gut microbiota to protect the BBB following stroke.
RESULTS
In IS treatment, SHT is principally involved in reducing neurological injury and the volume of cerebral infarction; protecting the intestinal mucosal barrier; increasing the levels of acetic acid, butyric acid, and propionic acid; promoting the transformation of microglia to the M2 state; reducing inflammatory reactions; and enhancing tight junctions. These therapeutic effects were not observed in the group treated with antibiotics alone or that treated with SHT in combination with antibiotics, thereby indicating SHT plays a therapeutic role through the gut microbiota.
CONCLUSION
SHT regulates the gut microbiota, inhibits pro-inflammatory factors in rats with IS, alleviates an inflammatory injury of the BBB, and plays a protective role in the brain.
Topics: Rats; Animals; Blood-Brain Barrier; Ischemic Stroke; Microglia; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Stroke; Tight Junction Proteins; Anti-Bacterial Agents
PubMed: 37196812
DOI: 10.1016/j.jep.2023.116640 -
Clinical Microbiology and Infection :... Apr 2024The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could...
OBJECTIVES
The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints.
METHODS
We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n = 30) and compared them with subjects fully recovered from acute COVID-19 (n = 14) and with individuals never infected (n = 16). We evaluated the structure and function of the vagus nerve and respiratory muscles.
RESULTS
Participants were mostly women (24 of 30, 80%), and the median age was 44 years (interquartile range [IQR] 35-51 years). Their most prevalent symptoms were cognitive dysfunction 25 of 30 (83%), dyspnea 24 of 30 (80%), and tachycardia 24 of 30 (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (cross-sectional area [CSA] [mean ± standard deviation]: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2; p 0.08), reduced esophageal-gastric-intestinal peristalsis (34% vs. 0% vs. 21%; p 0.02), gastroesophageal reflux (34% vs. 19% vs. 7%; p 0.13), and hiatal hernia (25% vs. 0% vs. 7%; p 0.05). Subjects with PCC showed flattening hemidiaphragms (47% vs. 6% vs. 14%; p 0.007), and reductions in maximum inspiratory pressure (62% vs. 6% vs. 17%; p ≤ 0.001), indicating respiratory muscle weakness. The latter findings suggest additional involvement of the phrenic nerve.
DISCUSSION
Vagus and phrenic nerve dysfunction contribute to the complex and multifactorial pathophysiology of PCC.
Topics: Humans; Female; Adult; Middle Aged; Male; COVID-19; Cross-Sectional Studies; SARS-CoV-2; Pilot Projects; Vagus Nerve; Post-Acute COVID-19 Syndrome; Dyspnea; Tachycardia
PubMed: 37984511
DOI: 10.1016/j.cmi.2023.11.007 -
The American Journal of Gastroenterology Aug 2023High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We...
INTRODUCTION
High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations.
METHODS
Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard.
RESULTS
Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%).
DISCUSSION
Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.
Topics: Humans; Reproducibility of Results; Esophageal Motility Disorders; Esophagogastric Junction; Manometry; Peristalsis; Esophageal Achalasia
PubMed: 37042784
DOI: 10.14309/ajg.0000000000002285