Effects of water ingestion on autonomic activity and gastric motility in patients with celiac disease.

The pathogenesis of celiac disease is associated with an autoimmune process. The disease causes chronic inflammation of the small intestinal mucosa, which may affect the brain-gut axis. The activation of visceral receptors (gastrointestinal mechanoreceptor and osmoreceptor) in response to stomach distension caused by water ingestion has not been studied before. Our results showed reduced responsiveness of the autonomic nervous system to water ingestion in patients with celiac disease, which may lead to disturbances of gastric myoelectrical activity and depends on baseline autonomic activity. Water intake can induce gastric distension and motility response, without changes in gastrointestinal hormones. It can also increase the activity of the autonomic nervous system. On the other hand, inflammation in celiac disease (CeD) can alter visceral perception (increase sensitization), leading to autonomic dysfunction. We aimed to investigate the effect of water ingestion on autonomic activity measured as heart rate variability (HRV) and gastric myoelectrical activity measured by electrogastrography (EGG) in patients with CeD. The study included 53 patients with CeD and 50 healthy controls: mean (SD) age, 43.4 (14.8) years and 44.1 (9.2) years, respectively. Electrocardiography with HRV analysis and simultaneous 4-channel EGG was performed before and after the water load test (WLT) ingestion 500-ml water over 5 minutes. We found that compared with controls, at fasting, patients with CeD showed a reduced percentage of normogastria (P=0.045) and an average percentage of slow wave coupling (P<0.01) with increased dominant power (DP) (P<0.001). Moreover, water ingestion in CeD patients reduced the percentage of gastric arrhythmia (P<0.01) and increased the percentage of normogastria (P<0.01) and DP (P<0.01). Finally, in the CeD group, water ingestion increased HRV indices: low frequency by 116.9% (P<0.001), high frequency by 125.3% (P<0.01), but they did not reach the values of the control group. Patients with CeD showed a smaller increase in parasympathetic autonomic activity after the WLT than controls. Altered autonomic responsiveness may contribute to the disturbances of gastric myoelectrical activity and depends on baseline autonomic activity.

Short-chain fatty acids in the saliva of patients with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a condition characterized by persistent symptoms and complications resulting from reflux of gastric contents into the esophagus. Short-chain fatty acids (SCFAs) are fermentation products of dietary fibres by the gut microbiota and are often studied for their anti-inflammatory and anticancer effects. The presence of SCFAs in the upper gastrointestinal tract, including in patients with GERD, has not been previously studied. The aim of this study was to investigate the relationship between the concentrations of SCFAs in the saliva of different age groups of patients with GERD. The study included 86 patients diagnosed with GERD, divided into two groups according to age: under and over 60 years of age, treated in the Gastroenterology and Hepatology Outpatient Clinic of the University Hospital in Cracow and 39 patients without gastrointestinal tract diseases. After clinical examination, blood was drawn to determine complete blood count, haemoglobin, and CRP. The oral cavity was examined, and unstimulated mixed saliva was collected. The SCFAs analysis was made by liquid chromatography-tandem mass spectrometry after facile derivatization coupled with liquid-liquid extraction. Of the six SCAFs studied, the highest median concentrations of acetic acid and propionic acid were observed in the saliva of patients with GERD and in the control group, in both the younger and older groups of patients. The concentrations of acetic acid and propionic acid were also higher compared with the four other fatty acids in the saliva of patients with GERD and in the control subjects. There were no correlations between salivary SCFAs levels and selected clinical and endoscopic parameters, including chronic inflammatory changes of the esophagus and stomach. In conclusions: SCFAs are present in the saliva of patients with GERD and in the control healthy persons. With the exception of valeric and isovaleric acids, salivary levels of SCFAs were significantly higher in patients with GERD compared to the control group. The highest concentrations of acetic acid and propionic acid were observed in patients with GERD and in both the younger and older patient groups. There were no differences in the concentrations of SCFAs in the saliva of female and male groups. We found no correlations between salivary SCFAs levels and selected clinical, laboratory and endoscopic changes of the oesophagus and stomach.

Disturbances of autonomic nervous system activity and diminished response to stress in patients with celiac disease.

Celiac disease (CED) is immune-mediated enteropathy caused by gluten intolerance affecting genetically predisposed individuals. CED may exert a number of various symptoms, including extra intestinal manifestations. Neurological symptoms can be the first sign of gluten intolerance. However, affected autonomic nervous system (ANS) activity may be linked to other symptoms. We evaluated the frequency of ANS impairment and resting ANS response to several stimuli in CED patients without neurological manifestations. Twenty five neurologically asymptomatic patients with CED were studied. The medical history was taken and ANS activity was determined. ANS tests included heart rate variability (HRV) at rest and after stimulation (sympathetic - stress, and parasympathetic - deep breathing). The results were compared with those of the control group comprising of 30 healthy asymptomatic volunteers. Both the resting HRV parameters and the HRV indices recorded after deep breathing (parasympathetic stimulation) were significantly lower in patients with CED than in the controls (P<0.05). Also the stress-induced increase in normalized low frequency parameter (LFnu) was significantly lower in the CED group than in the control group (P<0.05). Overall, about 20% of CED patients presented with parasympathetic dominancy but 36% with sympathetic dominancy, and 44% of patients did not show changes in sympathetic-vagal balance of the autonomic nervous system. We conclude that sympathetic-parasympathetic imbalance, in favour of more often sympathetic than parasympathetic overactivity occurs among neurologically asymptomatic CED patients. The ANS impairment observed in the course of CED may result from prolonged intestinal inflammation. Therefore, routine ANS testing might be considered in patients presenting with this condition.

Antibiotic treatment with ampicillin accelerates the healing of colonic damage impaired by aspirin and coxib in the experimental colitis. Importance of intestinal bacteria, colonic microcirculation and proinflammatory cytokines.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory, analgesic and antipyretic effects, however their use is associated with the broad spectrum of side effects observed in human as well as the experimental animals. Despite damaging activity of NSAIDs in upper gastrointestinal (GI) tract, these drugs exert deleterious influence in lower GI tract, including colon. The role of GI microflora in the pathogenesis of NSAIDs-induced experimental colonic damage is not completely understood. The aim of this study was 1) to evaluate the relative importance of the GI microflora on the experimental colonic damage in the presence of caused by NSAID, and 2) to assess the efficacy of antibiotic treatment with ampicillin on the process of healing of colitis. We compared the effect of vehicle, ASA applied 40 mg/kg intragastrically (i.g.) or the selective cyclooxygenase (COX)-2 inhibitor, celecoxib (25 mg/kg i.g.) without or with ampicillin treatment (800 mg/kg i.g.) administered throughout the period of 10 days, on the intensity of TNBS-induced colitis in rats. The severity of colonic damage, the alterations in the colonic blood flow (CBF) and myeloperoxidase (MPO) activity, the mucosal expression of TNF-α, IL-1ß, COX-2, VEGF and iNOS and the plasma concentration of TNF-α and IL-1ß were assessed. In all rats, the faeces samples as well as those from the colonic mucosa, blood, liver and spleen underwent microbiological evaluation for intestinal bacterial species including Escherichia coli and Enterococcus spp. The administration of TNBS resulted in macroscopic and microscopic lesions accompanied by the significant fall in the CBF, an increase in tissue weight and 4-5-fold rise in the MPO activity and a significant increase in the plasma IL-1ß and TNF-α levels. ASA or celecoxib significantly increased the area of colonic lesions, enhanced MPO activity and caused the marked increase in colonic tissue weight and plasma IL-1ß and TNF-α levels, as well as an overexpression of mRNA for IL-1ß and TNF-α, COX-2, VEGF and iNOS in the colonic tissue. ASA and coxib also resulted also in a significant increase of E. coli counts in the stool at day 3 and day 10 day of the observation compared with the intact rats. Moreover, E. coli translocation from the colon to the blood and extraintestinal organs such as liver and spleen in the group of rats treated without or with ASA and coxib. E. coli was the most common bacteria isolated from these organs. Treatment with ampicillin significantly attenuated the ASA- or celecoxib-induced increase in plasma levels of IL-1ß and TNF-α and suppressed the mucosal mRNA expression for IL-1ß and TNF-ß, COX-2, iNOS and VEGF in the colonic mucosa. Ampicillin administration caused a significant fall in the number of E. coli in the faeces at day 3 and day 10 of observation in ASA- and coxib-treated rats with colitis. Antibiotic therapy markedly reduced bacterial translocation to the colonic tissue and the extraintestinal organs such as the liver and spleen. We conclude that administration of ASA and to lesser extent of celecoxib, delays the healing of experimental colitis and enhances the alterations in colonic blood flow, proinflammatory markers such as IL-1ß, TNF-α, COX-2, iNOS and VEGF and increased intestinal mucosal permeability resulting in the intestinal bacterial translocation to the blood, spleen and liver. Antibiotic treatment with ampicillin is effective in the diminishing of the severity of colonic damage, counteracts both the NSAID-induced fall in colonic microcirculation and bacterial E.coli translocation to the extraintestinal organs.

Effect of Candida colonization on human ulcerative colitis and the healing of inflammatory changes of the colon in the experimental model of colitis ulcerosa.

The influence of fungal colonization on the course of ulcerative colitis (UC) has not been thoroughly studied. We determined the activity of the disease using clinical, endoscopic and histological index (IACH) criteria in UC patients with fungal colonization and the healing process of UC induced by an intrarectal administration of trinitrobenzene sulfonic acid (TNBS) in rats infected with Candida, without and with antifungal (fluconazole) or probiotic (lacidofil) treatment. The intensity of the healing of the colonic lesions was assessed by macro- and microscopic criteria as well as functional alterations in colonic blood flow (CBF). Myeloperoxidase (MPO) content and plasma proinflammatory cytokines IL-1beta and TNF-alpha levels were evaluated. Candida more frequently colonized patients with a history of UC within a 5-year period, when compared with those of shorter duration of IBS. Among Candida strains colonizing intestinal mucosa, Candida albicans was identified in 91% of cases. Significant inhibition of the UC activity index as reflected by clinical, endoscopical and histological criteria was observed in the Candida group treated with fluconazole, when compared to that without antifungal treatment. In the animal model, Candida infection significantly delayed the healing of TNBS-induced UC, decreased the CBF and raised the plasma IL-1beta and TNF-alpha levels, with these effects reversed by fluconazole or lacidofil treatment. We conclude that 1) Candida delays healing of UC in both humans and that induced by TNBS in rats, and 2) antifungal therapy and probiotic treatment during Candida infection could be beneficial in the restoration and healing of colonic damage in UC.

Assessment of co-existence of Helicobacter pylori and Candida fungi in diseases of the upper gastrointestinal tract.

Candida spp. were found in the gastric mucosa of 27 (17%) patients, out of whom 18 (11%) showed co-existence of the fungi with H. pylori. Analysis of relationship between selected disorders of the upper gastrointestinal tract (non ulcer dyspepsia NUD, gastric ulcer, duodenal ulcer) and infection with H. pylori and/or Candida revealed a link between co-existence of H. pylori with Candida and gastric ulcers suggesting synergism of those microorganism in pathogenesis of the disease. On the contrary, according to quantitative studies performed, the fungi alone do not play a significant role in pathogenesis of the above mentioned disorders as they colonize only epithelium to the extent that is not pathologically significant (<10(3) CFU/ml). Genetical study was carried out on 57 Helicobacter pylori strains isolated from bioptates of the gastric mucosa. The genotypes of the strains (gene cagA and alleles of gene vacA - m1, m2, s1, s2) were determined using the PCR technique. As it was shown, the patients infected with H. pylori strains of genotype cagA+, vacA s1 are exposed to higher risk of peptic ulcer disease (PUD) as compared to the patients infected with cagA-, vacA s2 strains. In the case of the NUD patients a correlation with allele m2 was found only (p<0.001). This may suggest that in future some of the NUD patients infected with cagA+, vacA s1 strains will fall into the group at higher risk for PUD.

Overexpression of the fragile histidine triad (FHIT) gene in inflammatory bowel disease.

OBJECTIVE: FHIT gene encodes human diadenosine triphosphate hydrolase involved in the regulation of cell cycle and nucleotide metabolism and is a candidate tumor suppressor gene. AIM: To investigate expression of FHIT gene at the mRNA and protein levels in sporadic inflammatory bowel disease (IBD). MATERIALS AND METHODS: FHIT mRNA was quantified by the validated real-time PCR (QPCR) and FHIT protein was detected by immunohistochemistry (IHC) in mucosal biopsies of 139 ulcerative colitis (UC), 19 Crohn's disease (CD) and 37 control patients. RESULTS: Significant FHIT gene overexpression was found in 78% of active UC but not in CD. IHC showed comparable results to QPCR. CONCLUSION: The local up-regulation of FHIT gene and protein expression in active UC may represent an adequate response against inflammatory challenge of epithelial cell homeostasis and protect against DNA damage and cell cycle disturbances.

Are probiotics effective in the treatment of fungal colonization of the gastrointestinal tract? Experimental and clinical studies.

UNLABELLED: The influence of fungal colonization and probiotic treatment on the course of gastric ulcer (GU) and ulcerative colitis (UC) was not explored. Our studies included: 1) clinical investigation of 293 patients with dyspeptic and ulcer complaints and 72 patients with lower gastrointestinal (GI) tract: 60 patients with UC, 12 with irritable bowel syndrome (IBS) - the control group. Significant fungal colonization (SFC), over 10(5) CFU/ml was evaluated. Mycological investigation was performed, including qualitative and quantitative examination, according to Muller method, 2) experimental studies in rats included estimation of the influence of inoculation of Candida isolated from human GI tract on the healing process of GU, induced by acetic acid with or without probiotic Lactobacillus acidophilus (10(6) CFU/ml) introduced intragastrically (i.g.). At 0, 4, 15 and 25 day after ulcer induction. Weight, damage area, gastric blood flow (GBF) (H2 clearance), expression of mRNA for cytokines IL-beta, TNF-alpha (ELISA) were evaluated. Mycology: qualitative and quantitative examination was performed. MPO serum activity was measured. Results of clinical studies: 1) SFC was more frequent in patients with GU: 54.2% of cases and patients with over 5 years history of UC: 33.3% cases. 2) SFC delayed GU healing and influenced the maintenance of clinical symptoms in both diseases. Results of animal studies: 3) In Candida inoculated rats, the GBF was significantly lower than in the vehicle controls (saline administered group). Upregulation of TNF-alpha, IL-1 beta was recorded. The GUs were still present till 25 day in all rats inoculated with Candida, in contrast to vehicle group (reduction of ulcer in 92% at day 25). CONCLUSIONS: 1) Fungal colonization delays process of ulcer and inflammation healing of GI tract mucosa. That effect was attenuated by probiotic therapy. 2) Probiotic therapy seems to be effective in treatment of fungal colonization of GI tract. 3) Lactobacillus acidophilus therapy shortens the duration of fungal colonization of mucosa (enhanced Candida clearance is associated with IL-4, INF-gamma response).

Fungal colonization of gastric mucosa and its clinical relevance.

BACKGROUND: The aim of our study was to evaluate the incidence of fungi in the stomach in patients with gastric ulcer and chronic gastritis in comparison to healthy humans, and to identify the fungus species isolated from these patients and their susceptibility to antifungal agents. We also assessed the coincidence of the presence of antifungal antibodies and fungal mannan antigen in serum with the concentration of fungi in the stomach. MATERIAL AND METHODS: We investigated 293 patients, aged 20-80, who visited the Gastroenterology Outpatient Clinic at the Jagellonian University's Collegium Medicum in Cracow, complaining of dyspeptic symptoms or clinical manifestations of ulcer disease. The examinations included endoscopy of the upper part of the alimentary tract with sampling of gastric contents, as well as surface brushing and biopsy from the bottom of the ulceration for mycological analysis. Also, biopsy specimens from the margin of the ulceration or inflammatory mucosa were collected for histological examination and urease testing. RESULTS: Gastric mucosa and stomach contents are often an area of fungal colonization, which was detected in 54.2% of the gastric ulcer cases and 10.3% of the chronic gastritis cases. The most frequently isolated fungus species was Candida albicans, although other fungi, previously considered rare or uncommon, were also found. A difference in growth in vitro between the C. albicans, C. tropicalis and C. lusitaniae strains was discovered: C. albicans and C. tropicalis grew from pH 2.0, while C. lusitaniae grew from pH 3.0. This finding suggests differentiation in the properties of these fungi. CONCLUSIONS: The lack of correlation between the concentration of fungi, the titre of antifungal antibodies and the presence of fungal antigen in serum suggests that fungal colonization is secondary in nature.

Effect of fungal colonization of gastric mucosa on the course of gastric ulcers healing.

BACKGROUND: The aim of the study was to evaluate the effect of fungal colonization on the course of gastric ulcer disease with particular regard to regression of clinical symptoms and reduction in ulcer niche size. MATERIAL AND METHODS: The study was performed on the group of 293 patients, aged 20-80, with clinical symptoms of peptic ulcer disease, who attended Gastroenterology Outpatient Department of Collegium Medicum of Kraków Jagiellonian University. Endoscopy of the upper gastrointestinal tract was performed before and following a-4-week period of a standard anti-ulcerous treatment. During the examination aspirate of the stomach contents and surface brushing were collected. Moreover, biopsy specimens from the bottom of the ulcer or inflamed gastric mucosa were taken for mycological and histopathological examinations. According to contemporary recommendations eradication treatment of Helicobacter pylori was introduced in urease-positive patients with endoscopy-proved gastric ulcer. RESULTS AND CONCLUSIONS: The results of our research showed that fungal colonization of gastric ulcers impairs the course of ulcer healing. Moreover, it results in clinical symptoms maintenance as compared with ulcers with non-significant fungal cells count.

Fungal colonization of the stomach and its clinical relevance.

The aim of this study was to estimate the frequency of fungal colonization of the stomach of patients suffering from gastric ulcer (GU) and chronic gastritis (CG) and the influence of fungal colonization of the stomach on the process of ulcer healing. We investigated 293 patients aged 20-80 years. Before and after 4 weeks of sucralfate treatment they underwent endoscopy of the stomach, histological examination of biopsies taken from the ulcer margin or inflamed gastric mucosa and mycological examinations of the gastric juice, surface brushing and biopsies. The studies revealed a high concentration of fungi in 54.2% patients with GU and 10.3% with CG. Candida albicans was the most frequently isolated organism. Fungal colonization of the stomach impairs the process of gastric ulcer healing. Control examination after 4 weeks of sucralfate therapy showed the ratio of GU healing in 62% of patients with a high concentration of fungi in comparison with 78% of patients not colonized with fungi (P < 0.05). A significantly longer duration of ulcer symptoms in the group of patients with a high concentration of fungi in the stomach was also observed. There was no correlation between the level of fungal antibodies, of Candida antigen in the serum and the concentration of fungi in the stomach.