[Chronic heart failure: structural and microbiological changes in the colon].

AIM: To study microbiocenosis of the parietal layer of the colon and feces, concentrations of endotoxin and proinflammatory cytokines in patients with chronic heart failure (CHF) of different functional classes vs. healthy subjects of the same age. MATERIAL AND METHODS: The trial includes 37 patients with ischemic CHF and 13 healthy volunteers. The examination comprised 6-min walking test, echocardiographic evaluation of the left ventricular ejection fraction, clinical state by a special scale, assay for C-reactive protein, endotoxin, fecal seeding, colonoscopy with biopsy and seeding. RESULTS: Gram-negative flora in the colon and parietal layer occurred in high concentrations correlating with severity of CHF. The examinees with CHF of functional class III-IV had elevated levels of circulating endotoxin and serum C-reactive protein.

Current insights into the pathophysiology of irritable bowel syndrome.

Recent reports have emphasized the possible role of mucosal immune activation and inflammation in neuropathic changes in the pathophysiology of irritable bowel syndrome (IBS). However, novel findings using functional brain imaging techniques have underlined the importance of altered perception of visceral stimuli to symptom generation in IBS. These new developments have rekindled an old debate on peripheral versus central mechanisms in the pathophysiology of IBS. In this review we discuss the latest findings in light of these two concepts. In addition, we provide evidence for the hypothesis that, in the absence of alterations in endogenous pain modulation systems and changes in visceral perception, chronic inflammatory mucosal changes in the gut are not a plausible mechanism to explain the presence of chronic abdominal pain, a cardinal IBS symptom.

Role of food hypersensitivity in irritable bowel syndrome.

A significant proportion of IBS patients attribute their symptoms to adverse food reactions. Dietary elimination and re-challenge studies support the role of diet in the pathogenesis of IBS. The aetiopathogenesis of IBS is thought to be multifactorial involving an interaction between diet, infection, antibiotics and psychosocial factors. Serum IgE and IgG4 antibodies are elevated in food hypersensitivity induced atopic conditions and a similar mechanism has been postulated in IBS. Increased number of mast cells is present in the ileocaecal region of IBS patients. Once sensitized, they are capable of inducing secretory and sensorimotor abnormalities of the gut. The management of IBS is usually aimed at controlling symptoms, however, evaluation of food hypersensitivity may provide a useful adjunct in those with severe symptoms or a clear history of adverse food reaction. There are no well-established tests available but skin prick tests and food specific serum IgG4 and IgE antibodies may help in identifying the offending foods. Other options, which may be explored in individual cases, include sequential dietary exclusion, use of hypoallergenic diets, disodium cromoglycate and novel techniques such as colonoscopic allergen provocation test. Pathophysiology of hypersensitivity induced IBS has been discussed in the light of current data and a management algorithm has been proposed for managing food hypersensitivity in IBS.

Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats.

BACKGROUND AND AIMS: Short-chain fatty acid (SCFA) (especially butyrate) enemas are widely used to reduce symptoms associated with human inflammatory bowel disease. The purpose of this study was to evaluate their real effect on colonic sensitivity in rats. METHODS: The effects of saline and SCFA enemas (acetate, propionate and particularly butyrate) were studied on visceral pain thresholds following colonic distension in control rats and in rats with colitis (instilled with trinitrobenzene sulfonic acid (TNBS)). RESULTS: Butyrate enemas (40 mM twice daily for 14 days) decreased colonic pain thresholds in control rats; they did not reduce the TNBS-induced hypersensitivity, but on the contrary increased its duration (without modifying the inflammation score). This pronociceptive effect was confirmed in control rats receiving twice daily enemas of 80 mM for 3 days and two enemas of 240 mM of a butyrate solution. The other SCFA enemas did not modify the hypersensitivity of rats with colitis and induced proinflammatory effects. CONCLUSIONS: The beneficial effect of SCFA (especially butyrate) enemas on hypersensitivity and inflammation in inflammatory bowel disease is questionable and needs to be thoroughly investigated in humans.

Natural killer cell function and psychological distress in women with and without irritable bowel syndrome.

The primary purpose of this exploratory study was to compare percentages of natural killer (NK) cells and activated NK and T cells, and both cytotoxic and in vitro cytokine production activity in women with and without symptomatic irritable bowel syndrome (IBS). A secondary purpose was to examine the relationships of psychological distress and low sense of coherence with immune function indicators and stress hormones. NK cell percentage and activity have been shown to vary in response to many psychological and physiological stressors. The authors compared 2 groups of women: symptomatic IBS (n = 12) and control (n = 12). Between-subject variability for all immune measures was large. The percentage of activated NK and Tcells was significantly lower in the IBS group compared to control (Mann-Whitney U = 30, P = 0.05). Relationships were significant between activated NK and T cell percentage and depression, anxiety, and overall distress (r = -0.54, -0.49, and -0.47, respectively, P < 0.03) and between interferon-gamma production and anxiety (r = -0.45, P < 0.03). There was a trend toward a positive relationship between sense of coherence and NK cytotoxicity (r = 0.39, P = 0.11). Thesefindings are important because they suggest that nursing interventions targeting ongoing physical and psychological distress might also be helpful in improving immune function.

A role for inflammation in irritable bowel syndrome?

Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.

Centrally acting agents and visceral sensitivity.

The evidence relating to the site and mechanism of action of "centrally acting" agents which may affect visceral sensitivity is reviewed. Antidepressant drugs such as amitriptyline as well as the newer selective serotonin reuptake inhibitors are thought to act at the level of the CNS. Opiates, including morphine as well as compounds such as trimebutine or fedotozine designed for therapeutic use in irritable bowel syndrome, are effective in reducing visceral nociception. Cytokines in the CNS are known to be involved in the modulation of pain and there is also evidence to suggest that centrally acting cytokines may play a role in the production of visceral hypersensitivity. Consequently, they may provide an interesting target for future research.

Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome.

BACKGROUND & AIMS: Abdominal symptoms in the absence of mucosal abnormalities are features of both the irritable bowel syndrome (IBS) and latent/potential celiac disease (cd). To identify a possible subgroup of IBS patients with latent/potential cd, surrogate markers of cd were investigated in IBS patients. METHODS: IBS patients suffering from diarrhea (n = 102), and patients with active cd (n = 10), treated cd (n = 26), and latent cd (n = 5) were included in the study. We measured serum immunoglobulin (Ig) A against gliadin and tissue-transglutaminase, and IgA and IgM against gliadin, tissue-transglutaminase (intestinal cd-associated antibodies), and the dietary proteins beta-lactoglobulin and ovalbumin in duodenal aspirate by enzyme-linked immunosorbent assay. Intraepithelial lymphocytes (IELs) were counted in histology sections, and the expression of HLA-DQ2 (A1*0501/B1*0201) was investigated by polymerase chain reaction. In 26 IBS patients, the effect of 6 months of gluten withdrawal was examined. RESULTS: Most cd patients expressed HLA-DQ2 and had increased intestinal cd-associated antibodies, whereas cd-associated serum IgA and IEL counts were increased in active cd in contrast to treated or latent cd. In IBS patients, 35% were HLA-DQ2-positive, 23% had increased IEL counts, and 0% and 30% had increased cd-associated antibodies in serum and duodenal aspirate, respectively. Furthermore, stool frequency and intestinal IgA decreased significantly under a gluten-free diet in the subgroups of HLA-DQ2-positive and intestinal antibody-positive IBS patients when compared with IBS patients without these markers. CONCLUSIONS: HLA-DQ2 expression and increased intestinal cd-associated antibodies are markers that can identify latent/potential cd in a subgroup of IBS patients who consequently appear to profit from a gluten-free diet.

Critical role for tumor necrosis factor alpha in controlling the number of lumenal pathogenic bacteria and immunopathology in infectious colitis.

Infection of mice with the intestinal bacterial pathogen Citrobacter rodentium results in colonic mucosal hyperplasia and a local Th1 inflammatory response similar to that seen in mouse models of inflammatory bowel disease. In these latter models, and in patients with Crohn's disease, neutralization of tumor necrosis factor alpha (TNF-alpha) is of therapeutic benefit. Since there is no information on the role of TNF-alpha in either immunity to noninvasive bacterial pathogens or on the role of TNF-alpha in the immunopathology of infectious colitis, we investigated C. rodentium infection in TNFRp55(-/-) mice. In TNFRp55(-/-) mice, there were higher colonic bacterial burdens, but the organisms were cleared at the same rate as C57BL/6 mice, showing that TNF-alpha is not needed for protective antibacterial immunity. The most striking feature of infection in TNFRp55(-/-) mice, however, was the markedly enhanced pathology, with increased mucosal weight and thickness, increased T-cell infiltrate, and a markedly greater mucosal Th1 response. Interleukin-12 p40 transcripts were markedly elevated in C. rodentium-infected TNFRp55(-/-) mice, and this was associated with enhanced mucosal STAT4 phosphorylation. TNF-alpha is not obligatory for protective immunity to C. rodentium in mice; however, it appears to play some role in downregulating mucosal pathology and Th1 immune responses.

H. pylori infection and visceral hypersensitivity in patients with irritable bowel syndrome.

BACKGROUND/AIM: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity (VH) is a key factor in the pathophysiology of IBS. The role of Helicobacter pylori infection in the induction of VH in the upper gastrointestinal tract is controversially discussed. The aim of this study is to evaluate the value of rectal barostat in eliciting abdominal symptoms in patients with IBS in relation to H. pylori infection. PATIENTS AND METHODS: 31 patients (19 female, 12 male, mean age 45.6 +/- 10 years) with normal colonoscopy and clinical signs of IBS were examined by rectal barostat (pressure-controlled balloon distension in the rectum). Induction of typical abdominal discomfort (far from the balloon) defined the examination positive. Level of nonpainful perception (L1), feeling of defecation (L2), and pain or stool urgency (L3) were registered in comparison with a healthy control group (CG; n = 15, 9 female, 6 male). The H. pylori status was defined by (13)C-urea breath test (n = 46). RESULTS: Typical abdominal discomfort was induced in 9 patients (pain group, PG) by pressure-controlled rectal distension (H. pylori status: 8 positive, 1 negative). Patients not presenting with abdominal pain to rectal distension (nonpain group, NPG) were all H. pylori negative (p < 0.001). L3 as an indicator of VH was reached at a lower pressure threshold in PG than in NPG or CG (p < 0.05). The perception was not different between NPG and CG (p > 0.05). CONCLUSIONS: The induction of typical abdominal discomfort in patients with IBS by the use of rectal barostat occurred predominantly in H. pylori infected patients and suggests that H. pylori infection may be involved in triggering VH in patients with IBS. Further studies in larger patient groups and after H. pylori eradication therapy are needed to confirm and extend this observation.