Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome

Camilleri, Michael; Andrews, Christopher N.; Bharucha, Adil E.; Carlson, Paula; Ferber, Irene; Stephens, Debra; Smyrk, Thomas C.; Urrutia, Raúl; Aerssens, Jeroen; Thielemans, Leen; Göhlmann, Hinrich W. H.; Wyngaert, Ilse Van den; Coulie, Bernard

doi:10.1053/j.gastro.2006.11.020

Cited by 113 publications

(80 citation statements)

References 28 publications

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“…Although Bellini et al (3) suggested that platelet SERT should reflect colonic SERT in IBS and observed a significant relationship with IBS-D, the assumption has not been validated or rigorously tested. Coates et al (16) suggested that there was an association between IBS-C or IBS-D and reduced SERT mRNA mucosal expression; however, we were unable to replicate the association between IBS symptom phenotype and SERT mRNA in sigmoid colon mucosa (7).…”

Section: Discussioncontrasting

confidence: 68%

Candidate genes and sensory functions in health and irritable bowel syndrome

Camilleri

Busciglio

Carlson

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Zinsmeister AR. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 295: 219 -225, 2008. First published May 29, 2008 doi:10.1152/ajpgi.90202.2008.-Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including ␣2A (C-1291G), ␣2C (Del 332-325), GN␤3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GN␤3 was associated only with fasting GV; we did not detect associations between ␣2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GN␤3 with fasting GV may explain, in part, the reported association of GN␤3 with dyspepsia. adrenergic; serotonergic; GN␤3; SLC6A4; G protein; receptor ADRENERGIC MECHANISMS alter gastrointestinal reflexes involved in intestinal propulsion, coordinated motor activity in the small bowel and colon, and gastrointestinal tone and fluid secretion (12,46). Norepinephrine is also involved in control of pain including supraspinal inhibition of pain, e.g., due to a change in the behavioral state (37) including stress, which contributes to gut motility disorders (10).Among ␣2 receptors, the ␣2A subtype appears to be critically important for control of motor functions, such as gastrointestinal transit in mice (40) and colonic circular smooth muscle in canine colon (47). The ␣2 receptor agonist, clonidine, inhibits gastric and colonic tone, phasic contractility, and sensation in the rectum and colon in response to balloon distension in healthy humans (4, 43).Serotonergic (5-HT) mechanisms also alter gut absorptive, motor, and sensory functions via actions in the gut, spinal cord, and brain stem (27). Ligand-receptor interaction results in c...

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Section: Discussioncontrasting

confidence: 68%

Candidate genes and sensory functions in health and irritable bowel syndrome

Camilleri

Busciglio

Carlson

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It is reported that in patients with IBS, the level of serotonin transporter protein mRNA and serotonin transporter protein decreased significantly in the intestinal epithelial cell 54) . Interestingly, these findings have not been proved in a current study 55) . But, some studies showed the description of a link between a protein critical to serotonin receptor functions and IBS 55) .…”

Section: Genetic Effectscontrasting

confidence: 91%

Functional Abdominal Pain in Children

Koh

2011

Korean J Pediatr Gastroenterol Nutr

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Functional abdominal pain (FAP) is one of the most common pain syndromes in childhood and is a functional gastrointestinal disorder (FGID). Recurrent abdominal pain (RAP) is characterized by three or more episodes of abdominal pain that occurover at least 3 months and are severe enough to interfere with activities. It may be caused by many conditions, including inflammatory bowel disease, peptic ulcer, pancreatitis or, functional abdominal pain. The most common clinical manifestation is periumbilical pain related to autonomic and functional symptoms like nausea, vomiting, pallor and other painful conditions like headache and limb pains. RAP requires accurate diagnostic tests to rule out organic causes of pain based on 'red flag' sign. Furthermore, to diagnose and classify functional abdominal pain, Rome III criteria were published and updated with multiple discussions of FGIDs. Conventional interventions for RAP include reassurance and general advice, symptom-based pharmacological therapies, and psychological and behavioral treatments. But further research should be conducted to advance our understanding of the multiple factors involved in the pathogenesis of this group of conditions and to provide evidence for its therapeutic benefit. (Korean J Pediatr Gastroenterol Nutr 2011; 14: 222∼231)

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“…paratuberculosis infection and disease in animals may reflect a specific mycobacterial neuropathogenicity. Microscopic inflammation affecting the enteric nervous system, together with abnormalities affecting its function and regulation, is well described in cases of IBS (2,4,11,19,25,51,69). Those studies have led to advances in our understanding of how these features integrate into the underlying pathophysiological mechanisms of the syndrome (3,32,48).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities

Scanu¹,

et al. 2007

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Mycobacterium avium subsp. paratuberculosis causes Johne's disease, a systemic infection and chronic inflammation of the intestine that affects many species, including primates. Infection is widespread in livestock, and human populations are exposed. Johne's disease is associated with immune dysregulation, with involvement of the enteric nervous system overlapping with features of irritable bowel syndrome in humans. The present study was designed to look for an association between Mycobacterium avium subsp. paratuberculosis infection and irritable bowel syndrome. Mucosal biopsy specimens from the ileum and the ascending and descending colon were obtained from patients with irritable bowel syndrome attending the University of Sassari, Sassari, Sardinia, Italy. Crohn's disease and healthy control groups were also included. Mycobacterium avium subsp. paratuberculosis was detected by IS900 PCR with amplicon sequencing. Data on the potential risk factors for human exposure to these pathogens and on isolates from Sardinian dairy sheep were also obtained. Mycobacterium avium subsp. paratuberculosis was detected in 15 of 20 (75%) patients with irritable bowel syndrome, 3 of 20 (15%) healthy controls, and 20 of 23 (87%) people with Crohn's disease (P ‫؍‬ 0.0003 for irritable bowel syndrome patients versus healthy controls and P ‫؍‬ 0.0000 for Crohn's disease patients versus healthy controls). One subject in each group had a conserved single-nucleotide polymorphism at position 247 of IS900 that was also found in isolates from seven of eight dairy sheep. There was a significant association (P ‫؍‬ 0.0018) between Mycobacterium avium subsp. paratuberculosis infection and the consumption of handmade cheese. Mycobacterium avium subsp. paratuberculosis is a candidate pathogen in the causation of a proportion of cases of irritable bowel syndrome as well as in Crohn's disease.

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Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome

Cited by 113 publications

References 28 publications

Candidate genes and sensory functions in health and irritable bowel syndrome

Candidate genes and sensory functions in health and irritable bowel syndrome

Functional Abdominal Pain in Children

Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities

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