Immunologically mediated hypersensitivity to foods is defined as food allergy, mainly due to immunglobulins of class E (IgE) triggering immediate reactions (type I hypersensitivity) with possible ...involvement of mucosa, skin, airways, intestinal tract, and the vascular system. Primary food allergy is based on (early) IgE sensitization against animal (e. g., cow's milk, hen's eggs) or plant proteins (e. g. peanut, hazelnut or wheat). In the case of secondary food allergies, IgE against pollen proteins (e. g., birch) reacts to structurally related food proteins (with cross-reactions to stone and pit fruits). Non-immunological food intolerance reactions are mostly based on carbohydrate malassimilation (e. g., lactose intolerance, fructose malabsorption) and are rarely due to pseudo-allergies (e. g., flavors, dyes, preservatives) primarily in patients with chronic urticaria. Common intestinal symptoms are mainly due to functional disorders (e. g., irritable bowel disease), rarely because of inflammatory intestinal diseases (e. g., celiac disease). Histamine intolerance, gluten hypersensitivity, and so-called food type III hypersensitivities are controversial diagnoses. The aforementioned disease entities/models are of variable importance for the affected individuals, the public health system, and society in general.
Abstract
Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT
4
receptors are promising candidates in IBS ...pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT
4
R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT
4
receptor gene
HTR4
to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms
HTR4b/i
and putatively impairs
HTR4
expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms.
In vitro
assays confirmed expression regulation via three 3′UTR binding sites. The novel isoform
HTR4b_2
lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that
HTR4
expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that
HTR4
might be involved in the development of IBS-D.
CCK inhibits the orexigenic effect of peripheral ghrelin Kobelt, Peter; Tebbe, Johannes J; Tjandra, Ines ...
American journal of physiology. Regulatory, integrative and comparative physiology
288, Številka:
3
Journal Article
Recenzirano
CCK and ghrelin exert antagonistic effects on ingestive behavior. The aim of the present study was to investigate the interaction between ghrelin and CCK administered peripherally on food intake and ...neuronal activity in specific hypothalamic and brain stem nuclei, as assessed by c-Fos-like immunoreactivity (c-FLI) in nonfasted rats. Ghrelin (13 microg/kg body wt) injected intraperitoneally significantly increased the cumulative food intake when measured at 30 min and 1 h after injection, compared with the vehicle group (2.9 +/- 1.0 g/kg body wt vs. 1.2 +/- 0.5 g/kg body wt, P < 0.028). Sulfated CCK octapeptide (CCK-8S) (2 or 25 microg/kg body wt) injected simultaneously blocked the orexigenic effect of ghrelin (0.22 +/- 0.13 g/kg body wt, P < 0.001 and 0.33 +/- 0.23 g/kg body wt, P < 0.0008), while injected alone, both doses of CCK-8S exerted a nonsignificant trend to reduce food intake. Ghrelin (13 microg/kg body wt ip) markedly increased the number of c-FLI-positive neurons per section in the arcuate nucleus (ARC) compared with vehicle (median: 31.35 vs. 9.86, P < 0.0001). CCK-8S (2 or 25 microg/kg body wt ip) had no effect on neuronal activity in the ARC, as assessed by c-FLI (median: 5.33 and 11.21 cells per section), but blocked the ghrelin-induced increase of c-fos expression in this area when both peptides were administered simultaneously (median: 13.33 and 12.86 cells per section, respectively). Ghrelin at this dose had no effect on CCK-induced stimulation of c-fos expression in the paraventricular nucleus of the hypothalamus and the nucleus of the solitary tract. These results suggest that CCK abolishes ghrelin-induced food intake through dampening increased ARC neuronal activity.
BACKGROUNDSingle-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations ...exist in irritable bowel syndrome (IBS). AIMTo assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODSIn this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTSDepressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSIONWe have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT
3
receptor family. 5-HT
3
Rs are encoded ...by
HTR3
genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT
3
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.
Functional Abdominal Pain Syndrome Clouse, Ray E.; Mayer, Emeran A.; Aziz, Qasim ...
Gastroenterology (New York, N.Y. 1943),
04/2006, Letnik:
130, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher ...comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogenous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.
It is well established that autonomic control of gastrointestinal function is modulated by central autonomic neurotransmission. In this context it has been shown that gastrointestinal motility and ...secretion can be modulated by exogenous neuropeptides microinjected into the paraventricular nucleus of the hypothalamus (PVN). Furthermore, there is considerable evidence suggesting that neurons projecting from the arcuate nucleus (Arc) to the PVN may be the source of endogenous neuropeptide release in the PVN. This poses the question whether stimulation of neurons in the arcuate nucleus, e.g. by an excitatory amino acid, alters gastrointestinal function. In the present study, we investigated the effect of an excitatory amino acid, kainate, microinjected into the arcuate nucleus on gastric acid secretion in urethane-anesthetized rats. Kainate (140 pmol/rat) bilaterally microinjected into the Arc induced an significant inhibition of pentagastrin (PG) stimulated (16 mg/kg per h) gastric acid secretion throughout an observation period of 120 min after microinjection. Microinjection of kainate into hypothalamic areas outside the arcuate nucleus did not modify gastric secretion. Bilateral cervical vagotomy blocked the effect of kainate injected into the Arc on PG-stimulated gastric acid secretion. These data show that gastric secretory function can be modulated by stimulation of neuronal activity in the Arc via efferent vagal pathways. The results suggest that the arcuate nucleus is a forebrain area involved in the CNS regulation of gastrointestinal function.
Background/AimsCarbohydrate malabsorption is frequent in patients with functional gastrointestinal disorders and in healthy volunteers and cancause gastrointestinal symptoms mimicking irritable bowel ...syndrome (IBS). The aim of this study was to investigate the prevalence ofsymptomatic lactose and fructose malabsorption in a large population of patients with IBS-like symptoms based on Rome II criteria. MethodsPatients with unclear abdominal discomfort (n = 2,390) underwent lactose (50 g) and fructose (50 g) hydrogen (H2) breathtests and depending on the results further testing with 25 g fructose or 50 g glucose, or upper endoscopy with duodenalbiopsies. Additionally, this population was investigated regarding the prevalence of small intestinal bacterial overgrowth (SIBO)based on glucose breath test and celiac disease. ResultsOf the 2,390 patients with IBS-like symptoms, 848 (35%) were symptomatic lactose malabsorbers and 1,531 (64%) symptomaticfructose malabsorbers. A combined symptomatic carbohydrate malabsorption was found in 587 (25%) patients. Severefructose malabsorbers (pathologic 25 g fructose test) exhaled significantly higher H2 concentrations in the 50 g test than patientswith negative 25 g fructose test (P < 0.001). Out of 460/659 patients with early significant H2 increase in the lactoseand fructose test who underwent a glucose breath test, 88 patients had positive results indicative of SIBO and they were significantlyolder than patients with negative test result (P < 0.01). Celiac disease was found in 1/161 patients by upper endoscopy. ConclusionsCarbohydrate malabsorption is a frequent but underestimated condition in patients with IBS-like symptoms although diagnosiscan be easily confirmed by H2 breath testing.
AIM： To investigate the influence of irritable bowel syndrome （IBS）-like symptoms on treatment outcomes with pantoprazole in gastroesophageal reflux disease （GERD） in a real life setting. METHODS： ...For this prospective, open-label, multinational, multicentre study, 1888 patients assessed by the investigators as suffering from GERD were recruited. The patients were additionally classified as with or without IBS-like symptoms at baseline. They were treated with pantoprazole 40 mg once daily and completed the Reflux Questionnaire （ReQuest） short version daily. Response rates and symptom scores were compared after 4 and 8 wk of treatment for subgroups defined by the subclasses of GERD erosive（ERD） and non-erosive reflux disease （NERD） and the presence of IBS-like symptoms. RESULTS： IBS-like symptoms were more prevalent in NERD than in ERD （18.3% vs 12.7%, P = 0.0015）. Response rates after 4 and/or 8 wk of treatment were lower in patients with IBS-like symptoms than in patients without IBS-like symptoms in both ERD （Week 4： P 〈 0.0001, Week 8： P 〈 0.0339） and NERD （Week 8： P = 0.0088）. At baseline, ReQuest ＂lower abdominal com- plaints＂ symptom scores were highest in NERD patients with IBS-like symptoms. Additionally, these patients had the strongest symptom improvement after treatment compared with all other subgroups. CONCLUSION： IBS-like symptoms influence treatment outcome and symptom burden in GERD and should be considered in management. Proton pump inhibitors can improve IBS-like symptoms, particularly in NERD.
Although the standard treatments for the irritable bowel syndrome (IBS) are medical, growing evidence indicates the substantial therapeutic value of psychological therapy. However, it has not been ...investigated whether the combination of multicomponent behavioral therapy plus medical treatment is more effective than medical treatment alone. The aim of this study was to investigate this question in patients consulting a tertiary gastrointestinal (GI) referral center.
Twenty-four IBS outpatients were randomly assigned to the combination of standardized multicomponent behavioral therapy plus standard medical treatment (SMBT) or standard medical treatment alone (SMT). SMBT included IBS information and education, progressive muscle relaxation, training in illness-related cognitive coping strategies, problem-solving, and assertiveness training in 10 sessions over 10 wk. SMT included standardized symptom-oriented medical treatment and regular visits to a gastroenterologist every second week. Posttreatment outcome measures consisted of quantification of GI, vegetative, and psychological symptoms by means of daily symptom diaries and the assessment of changes in rectovisceral perception thresholds, as well as of questionnaire measures on psychological distress, overall well-being, illness-related coping abilities, and quality of life. Follow-ups were conducted at 3- and 6-month intervals.
Pre- and posttreatment evaluations showed significantly (p < 0.01) greater IBS symptom reduction as measured by daily symptom diaries for the SMBT group than for the SMT group. Rectovisceral perception remained unchanged by either treatment. Overall well-being significantly improved in the SMBT group but remained unchanged in the SMT group. Subjects in the SMBT group, unlike those in the SMT group, felt significantly more in control of their health, and quality of life was significantly improved in the SMBT group but remained unchanged in the SMT group.
The data provide evidence that the combination of medical treatment plus multicomponent behavioral treatment is superior to medical treatment alone in the therapy of IBS.
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