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American Journal of Physiology.... Jan 2020Cyclical propagating waves of muscle contraction have been recorded in isolated small intestine or colon, referred to here as motor complexes (MCs). Small intestinal and...
Cyclical propagating waves of muscle contraction have been recorded in isolated small intestine or colon, referred to here as motor complexes (MCs). Small intestinal and colonic MCs are neurogenic, occur at similar frequencies, and propagate orally or aborally. Whether they can be coordinated between the different gut regions is unclear. Motor behavior of whole length mouse intestines, from duodenum to terminal rectum, was recorded by intraluminal multisensor catheter. Small intestinal MCs were recorded in 27/30 preparations, and colonic MCs were recorded in all preparations ( = 30) with similar frequencies (0.54 ± 0.03 and 0.58 ± 0.02 counts/min, respectively). MCs propagated across the ileo-colonic junction in 10/30 preparations, forming "full intestine" MCs. The cholinesterase inhibitor physostigmine increased the probability of a full intestine MC but had no significant effect on frequency, speed, or direction. Nitric oxide synthesis blockade by -nitro-l-arginine, after physostigmine, increased MC frequency in small intestine only. Hyoscine-resistant MCs were recorded in the colon but not small intestine ( = 5). All MCs were abolished by hexamethonium ( = 18) or tetrodotoxin ( = 2). The enteric neural mechanism required for motor complexes is present along the full length of both the small and large intestine. In some cases, colonic MCs can be initiated in the distal colon and propagate through the ileo-colonic junction, all the way to duodenum. In conclusion, the ileo-colonic junction provides functional neural continuity for propagating motor activity that originates in the small or large intestine. Intraluminal manometric recordings revealed motor complexes can propagate antegradely or retrogradely across the ileo-colonic junction, spanning the entire small and large intestines. The fundamental enteric neural mechanism(s) underlying cyclic motor complexes exists throughout the length of the small and large intestine.
Topics: Animals; Cholinergic Antagonists; Cholinesterase Inhibitors; Colon; Enteric Nervous System; Female; Ganglionic Blockers; In Vitro Techniques; Intestine, Small; Male; Mice, Inbred C57BL; Myoelectric Complex, Migrating; Peristalsis; Pressure; Time Factors
PubMed: 31709829
DOI: 10.1152/ajpgi.00185.2019 -
Neuropeptides Feb 2020Irritable bowel syndrome (IBS) is a common gastrointestinal disorder of unknown aetiology for which there is no effective treatment. Although IBS does not increase... (Review)
Review
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder of unknown aetiology for which there is no effective treatment. Although IBS does not increase mortality, it reduces the quality of life and is an economic burden to both the patients themselves and society as a whole. Peptide YY (PYY) is localized in endocrine cells located in the ileum, colon and rectum. The concentration of PYY and the density of PYY cells are decreased in both the colon and rectum but unchanged in the ileum of patients with IBS. The low density of PYY cells in the large intestine may be caused by a decreased number of stem cells and their progeny toward endocrine cells. PYY regulates the intestinal motility, secretion and absorption as well as visceral sensitivity via modulating serotonin release. An abnormality in PYY may therefore contribute to the intestinal dysmotility and visceral hypersensitivity seen in IBS patients. Diet management involving consuming a low-FODMAP diet restores the density of PYY cells in the large intestine and improves abdominal symptoms in patients with IBS. This review shows that diet management appears to be a valuable tool for correcting the PYY abnormalities in the large intestine of IBS patients in the clinic.
Topics: Colon; Gastrointestinal Motility; Humans; Irritable Bowel Syndrome; Peptide YY; Quality of Life; Serotonin
PubMed: 31727345
DOI: 10.1016/j.npep.2019.101973 -
Neurourology and Urodynamics Mar 2012Normal functioning of the urinary bladder and the distal gut is an essential part of daily physiological activity coordinated by the peripheral and central nervous... (Review)
Review
Normal functioning of the urinary bladder and the distal gut is an essential part of daily physiological activity coordinated by the peripheral and central nervous systems. Pathological changes in one of these organs may induce the development of cross-organ sensitization in the pelvis and underlie clinical co-morbidity of genitourinary and GI dysfunctions. Experimental human and animal data suggest that the bladder and distal colon interact under both normal and pathological conditions, however, the directions of these interactions can change dramatically depending on the nature and duration of the applied stimuli. This review article aimed to summarize the clinical data on colon-bladder cross-reflexes in healthy individuals, as well as in patients with co-morbid disorders. It also discusses currently used animal models, experimental approaches, and suggested mechanisms of colon-bladder cross-talk. Additionally, it provides an overview of the potential pharmacological targets to develop treatment options for patients with co-morbid disorders. Presented work resulted from the discussion of colon/bladder interactions during "Think Tank 9" presentations at the International Consultation on Incontinence Research Society meeting held in Bristol, UK, 2011.
Topics: Animals; Colon; Colonic Diseases; Comorbidity; Disease Models, Animal; Evidence-Based Medicine; Humans; Reflex; Urinary Bladder; Urinary Bladder Diseases
PubMed: 22378593
DOI: 10.1002/nau.21228 -
Annals of Surgery Jun 1986Controversy continues regarding the initial management of civilian colon injuries. The main issues are the safety of colostomy versus the desirability of primary repair...
Controversy continues regarding the initial management of civilian colon injuries. The main issues are the safety of colostomy versus the desirability of primary repair and the role of exteriorized repair. From 1979 through 1984, 727 patients with injuries to the colon were treated at a large urban trauma center. Ninety-seven per cent of injuries were caused by penetrating wounds. Ten patients died in the operating room prior to repair of the colon wound. For patients who survived long enough to have their injury treated, 52.4% were treated by primary repair, 32.9% were treated with colostomies, and 14.6% were treated with exteriorized repair. Of the factors that have been stated to influence decision making, the extent of the colon injury was the most important. Location, number, and type of associated injuries, fecal contamination, and shock were less important. However, none of these latter factors mandated performance of a colostomy. The overall mortality rate for the series was 9.9%. Forty-one out of 70 deaths occurred within the first 48 hours and were due to shock and hemorrhage. The mortality rate for primary repair was significantly lower than that for colostomies (p less than 0.01). The presence of shock and age greater than 40 were significant factors influencing mortality (p less than 0.01). Mortality also was directly related to the number and type of associated abdominal injuries. Abdominal abscess also occurred significantly less often in patients treated with primary repair than in those with colostomies (p less than 0.01). The use of exteriorized repair was successful in avoiding colostomy in 59% of patients. Primary repair can be performed with minimal morbidity and mortality and should be the mainstay of treatment for civilian colon injuries.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Colon; Colostomy; Female; Humans; Male; Middle Aged; Necrosis; Postoperative Complications; Pulmonary Atelectasis; Rectum
PubMed: 3718032
DOI: 10.1097/00000658-198606000-00016 -
Cellular and Molecular Gastroenterology... 2021p21-activated kinase-1 (PAK1) belongs to a family of serine-threonine kinases and contributes to cellular pathways such as nuclear factor-κB (NF-κB), mitogen-activated...
BACKGROUND & AIMS
p21-activated kinase-1 (PAK1) belongs to a family of serine-threonine kinases and contributes to cellular pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and Wingless-related integration site(Wnt)/β-catenin, all of which are involved in intestinal homeostasis. Overexpression of PAK1 is linked to inflammatory bowel disease as well as colitis-associated cancer (CAC), and similarly was observed in interleukin (IL)10 knockout (KO) mice, a model of colitis and CAC. Here, we tested the effects of PAK1 deletion on intestinal inflammation and carcinogenesis in IL10 KO mice.
METHODS
IL10/PAK1 double-knockout (DKO) mice were generated and development of colitis and CAC was analyzed. Large intestines were measured and prepared for histology or RNA isolation. Swiss rolls were stained with H&E and periodic acid-Schiff. Co-immunoprecipitation and immunofluorescence were performed using intestinal organoids, SW480, and normal human colon epithelial cells 1CT.
RESULTS
When compared with IL10 KO mice, DKOs showed longer colons and prolonged crypts, despite having higher inflammation and numbers of dysplasia. Crypt hyperproliferation was associated with Notch1 activation and diminished crypt differentiation, indicated by a reduction of goblet cells. Gene expression analysis indicated up-regulation of the Notch1 target hairy and enhancer of split-1 and the stem cell receptor leucin-rich repeat-containing G-protein-coupled receptor 5 in DKO mice. Interestingly, the stem cell marker olfactomedin-4 was present in colonic tissue. Increased β-catenin messenger RNA and cytoplasmic accumulation indicated aberrant Wnt signaling. Co-localization and direct interaction of Notch1 and PAK1 was found in colon epithelial cells. Notch1 activation abrogated this effect whereas silencing of PAK1 led to Notch1 activation.
CONCLUSIONS
PAK1 contributes to the regulation of crypt homeostasis under inflammatory conditions by controlling Notch1. This identifies a novel PAK1-Notch1 axis in intestinal pathophysiology of inflammatory bowel disease and CAC.
Topics: Animals; Cell Line; Colitis; Colitis-Associated Neoplasms; Colon; Disease Models, Animal; Female; Gene Silencing; Humans; Interleukin-10; Intestinal Mucosa; Male; Mice; Mice, Knockout; Organoids; Piroxicam; Primary Cell Culture; Receptor, Notch1; Up-Regulation; Wnt Signaling Pathway; p21-Activated Kinases
PubMed: 33189893
DOI: 10.1016/j.jcmgh.2020.11.001 -
Journal of Microbiology and... Feb 2020The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum...
The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum of mice were investigated through 16S rRNA high-throughput sequencing. The lowest bacterial diversity and evenness were observed in duodenal LM (D_LM), followed by duodenal MAM (D_MAM). Meanwhile, the bacterial diversity and evenness were obviously increased in D_MAM than these in D_LM, while no significant difference was observed between colonic MAM (C_MAM) and colonic LM (C_LM). PCoA analysis also showed that bacterial communities of LM and MAM in duodenum were completely separated, while these in colon overlapped partly. The ratio of Firmicutes to Bacteroidetes (F/B) in D_MAM was significantly higher than that in D_LM. was largely enriched and was the characteristic bacteria in D_LM. The characteristic bacteria in D_MAM were , and , while in C_LM they were _6, _9, _UCG_007 and _UCG_010, and in C_MAM they were _NK4A136, , , and . The networks showed that more interactions existed in colonic microbiota (24 nodes and 74 edges) than in duodenal microbiota (17 nodes and 29 edges). The 16S rDNA function prediction results indicated that bigger differences of function exist between LM and MAM in duodenum than these in colon. In conclusion, microbiota from intestinal luminal content and mucosa were different both in colon and in duodenum, and bacteria in colon interacted with each other much more closely than those in duodenum.
Topics: Animals; Bacteria; Biodiversity; Colon; Computational Biology; Duodenum; High-Throughput Nucleotide Sequencing; Intestinal Mucosa; Metagenome; Metagenomics; Mice; Microbiota; Mucous Membrane; Organ Specificity
PubMed: 31635444
DOI: 10.4014/jmb.1908.08037 -
Nutrients Aug 2010This paper reviews recent human studies on the bioavailability of chlorogenic acids in coffee and green tea flavan-3-ols in which the identification of metabolites,... (Review)
Review
This paper reviews recent human studies on the bioavailability of chlorogenic acids in coffee and green tea flavan-3-ols in which the identification of metabolites, catabolites and parent compounds in plasma, urine and ileal fluid was based on mass spectrometric methodology. Both the chlorogenic acids and the flavan-3-ols are absorbed in the small intestine and appear in the circulatory system predominantly as glucuronide, sulfate and methylated metabolites. Even when absorption occurs in the small intestine, feeding studies with ileostomists reveal that substantial amounts of the parent compounds and some of their metabolites appear in ileal fluid indicating that in volunteers with a functioning colon these compounds will pass to the large intestine where they are subjected to the action of the colonic microflora. A diversity of colonic-derived catabolites are absorbed into the bloodstream and pass through the body prior to excretion in urine. There is growing evidence that these compounds, which were little investigated until recently, are produced in quantity in the colon and form a key part of the bioavailability equation of flavonoids and related compounds that occur in fruits, vegetables and beverages. Recent evidence indicates that some colon-derived phenolic acids have in vitro anti-inflammatory activity.
Topics: Biological Availability; Chlorogenic Acid; Coffee; Colon; Flavonoids; Humans; Hydroxybenzoates; Intestinal Absorption; Mass Spectrometry; Tea
PubMed: 22254058
DOI: 10.3390/nu2080820 -
American Journal of Physiology.... Jan 2021Motility of the large bowel may be grossly subdivided in two types of contractile activity: low-amplitude single or cyclic propagated waves and high-amplitude propagated... (Review)
Review
Motility of the large bowel may be grossly subdivided in two types of contractile activity: low-amplitude single or cyclic propagated waves and high-amplitude propagated activity. The latter is mainly apt to shift relatively large amounts of colonic contents, and it is related to defecation. The main component of this propagated activity is represented by the radiologically identified mass movements that have a manometric equivalent known as high-amplitude propagated contractions (HAPC). The present article reviews origins and characterization of HAPC in the time course of colonic motility investigations, and correlates it with technological advancements in recent years, putting into perspective the future possible options to better detect and investigate these important physiological events.
Topics: Colon; Colonic Neoplasms; Gastrointestinal Motility; Humans; Manometry; Muscle Contraction
PubMed: 33174455
DOI: 10.1152/ajpgi.00375.2020 -
Neurogastroenterology and Motility Apr 20215-HT receptor (5-HT R) agonists exert prokinetic actions in the GI tract, but non-selective actions and potential for stimulation of non-target 5-HT Rs have limited...
BACKGROUND
5-HT receptor (5-HT R) agonists exert prokinetic actions in the GI tract, but non-selective actions and potential for stimulation of non-target 5-HT Rs have limited their use. Since 5-HT Rs are expressed in the colonic epithelium and their stimulation accelerates colonic propulsion in vitro, we tested whether luminally acting 5-HT R agonists promote intestinal motility.
METHODS
Non-absorbed 5-HT R agonists, based on prucalopride and naronapride, were assessed for potency at the 5-HT R in vitro, and for tissue and serum distribution in vivo in mice. In vivo assessment of prokinetic potential included whole gut transit, colonic motility, fecal output, and fecal water content. Colonic motility was also studied ex vivo in mice treated in vivo. Immunofluorescence was used to evaluate receptor distribution in human intestinal mucosa.
KEY RESULTS
Pharmacological screening demonstrated selectivity and potency of test agonists for 5-HT R. Bioavailability studies showed negligible serum detection. Gavage of agonists caused faster whole gut transit and colonic motility, increased fecal output, and elevated fecal water content. Prokinetic actions were blocked by a 5-HT R antagonist and were not detected in 5-HT R knockout mice. Agonist administration promoted motility in models of constipation. Evaluation of motility patterns ex vivo revealed enhanced contractility in the middle and distal colon. Immunoreactivity for 5-HT R is present in the epithelial layer of the human small and large intestines.
CONCLUSIONS AND INFERENCES
These findings demonstrated that stimulation of epithelial 5-HT Rs can potentiate propulsive motility and support the concept that mucosal 5-HT Rs could represent a safe and effective therapeutic target for the treatment of constipation.
Topics: Animals; CHO Cells; Colon; Constipation; Cricetinae; Cricetulus; Gastrointestinal Motility; Humans; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists
PubMed: 33185015
DOI: 10.1111/nmo.14026 -
Comptes Rendus Biologies Dec 2021The colon is primarily responsible for absorbing fluids. It contains a large number of microorganisms including fungi, which are enriched in its distal segment. The...
The colon is primarily responsible for absorbing fluids. It contains a large number of microorganisms including fungi, which are enriched in its distal segment. The colonic mucosa must therefore tightly regulate fluid influx to control absorption of fungal metabolites, which can be toxic to epithelial cells and lead to barrier dysfunction. How this is achieved remains unknown. Here, we describe a mechanism by which the innate immune system allows rapid quality-check of absorbed fluids to avoid intoxication of colonocytes. This mechanism relies on a population of distal colon macrophages that are equipped with "balloon-like" protrusions (BLPs) inserted in the epithelium, which sample absorbed fluids. In the absence of macrophages or BLPs, epithelial cells keep absorbing fluids containing fungal products, leading to their death and subsequent loss of epithelial barrier integrity. These results reveal an unexpected and essential role of macrophages in the maintenance of colon-microbiota interactions in homeostasis.
Topics: Colon; Epithelial Cells; Homeostasis; Intestinal Mucosa; Macrophages
PubMed: 35787605
DOI: 10.5802/crbiol.67