The serotonin receptor 3E variant is a risk factor for female IBS-D

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D

The serotonin receptor 3E variant is a risk factor for female IBS-D

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT receptor family. 5-HT Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D. [Abstract copyright: © 2022. The Author(s).

Molecular mechanisms of gastrointestinal protection by quercetin against indomethacin-induced damage: Role of NF-κB and Nrf2

© 2015 Elsevier Inc.The aim of this study was to determine the gastrointestinal protection by quercetin against indomethacin-induced oxidative stress and inflammation, with specific interest in studying the underlying molecular mechanisms. We hypothesized that the quercetin-protective effect relies on its antioxidant and antiinflammatory properties. Rats were pretreated with quercetin (50- or 100-mg/kg, ig single dose), 30 min before INDO administration (40-mg/kg ig single dose). Caco-2 cells were treated with INDO (250 and 500 μM) in the absence or presence of quercetin (10 μg/ml). Quercetin prevented the decrease in nuclear translocation of Nrf2, a key regulator of the antioxidant response, and the increase in reactive oxygen species levels induced by INDO by inhibiting the enhancement of NADPH oxidase and xanthine oxidase activities as well as the reduction in superoxide dismutase and glutathione peroxidase activities in gastric and ileal tissues. Quercetin also prevented INDO-indu

Possible association between mycobacterium avium subsp paratuberculosis infection and crohn's disease Mycobacterium avium subsp paratuberculosis y enfermedad de crohn: Evidencias de una zoonosis

Paratuberculosis is a chronic intestinal disease of animals caused by Mycobacterium avium subsp. paratuberculosis (MAP), which has some pathological features similar to Crohn's disease (CD) in humans. The presence of MAP in food for human consumption and in affected tissues of patients with CD has been detected. Therefore, a causal association between this microorganism and the disease in humans, has been postulated. However, several related studies have failed to confirm this hypothesis and the scientific acceptance of MAP as a zoonotic agent remains controversial. This review presents the main findings related to this issue, contrasting evidences for and against an association between MAP and CD. The need to promote national studies focusing on this area is suggested

Activación de mastocitos en el intestino, una de las causas orgánicas en el síndrome de intestino irritable

Irritable bowel syndrome (IBS) is one of the most common digestive health conditions in Chile as in the Western society, which is characterized by abdominal discomfort associated with alterations in bowel habit, that lead to increased visceral hypersensitivity. It has a significant impact on our country’s social welfare and economic development, due to great deterioration in the patient’s quality of life. Although the pathophysiology of IBS is unclear, the gut-brain axis disequilibrium is involved in the disease onset. Psychosocial factors, such as stress and depression, have been linked to altered immune responses as enhanced intestinal mast cell activation, in proximity to colonic nerves, correlate with abdominal pain in IBS. This review is a brief summary of the role of increased mast cell activity in IBS, focusing specifically on influences over epithelial and neural function at the intestinal mucosa. The most promising preliminary therapeutics approaches, directed to reduce mast cell activation, are also included in this review

Peripheral cytokine profile in Chilean patients with Crohn's disease and ulcerative colitis

Crohn's disease (CD) and ulcerative colitis (UC) belong to the group of inflammatory bowel diseases (IBD), with complex ethiopathogenic factors that include an unbalanced immune and inflammatory response to commensal and food antigens. The differential diagnosis between CD and UC is performed using clinical, endoscopic, histopathological, serological and radiological methods; however between 10-15% of IBD patients are diagnosed as "unclassified colitis". Further research into IBD is necessary in order to develop additional diagnostic tools. The aim of this work was to see if the Th1, Th17 or Th2 immune pattern, represented by CD4 + lymphocytes producing IFN-γ, IL-17 and IL-5 or IL-13, respectively (CD4/IFN-γ+, CD4/IL-17+,CD4/IL-5+ or, CD4/IL13+), are useful peripheral markers which can be used to differentiate between UC and CD. Peripheral blood samples were taken from IBD patients from the Clinic Hospital of the University of Chile. The percentage of IFN-γ-, IL-17-, IL-5- or IL-13-ex

Toll-like Receptors are Key Participants in Innate Immune Responses

During an infection, one of the principal challenges for the host is to detect the pathogen and activate a rapid defensive response. The Toll-like family of receptors (TLRs), among other pattern recognition receptors (PRR), performs this detection process in vertebrate and invertebrate organisms. These type I transmembrane receptors identify microbial conserved structures or pathogen-associated molecular patterns (PAMPs). Recognition of microbial components by TLRs initiates signaling transduction pathways that induce gene expression. These gene products regulate innate immune responses and further develop an antigen-specific acquired immunity. TLR signaling pathways are regulated by intracellular adaptor molecules, such as MyD88, TIRAP/Mal, between others that provide specificity of individual TLR- mediated signaling pathways. TLR-mediated activation of innate immunity is involved not only in host defense against pathogens but also in immune disorders. The involvement of TLR-mediated pathways in auto-immune and inflammatory diseases is described in this review articl

Inflammatory bowel diseases: An immunological approach Enfermedad inflamatoria intestinal: Una mirada inmunológica

Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predom