Small intestinal bacterial overgrowth is associated with irritable bowel syndrome and is independent of proton pump inhibitor usage.

BACKGROUND: Current knowledge suggests that small intestinal overgrowth participates in the pathogenesis of irritable bowel syndrome. It is questionable if this association is modulated by intake of proton pump inhibitors (PPIs). METHODS: In a prospective study, quantitative cultures of duodenal aspirates were performed for aerobic species in 897 consecutive patients undergoing upper GI tract endoscopy. SIBO was defined as equal to or more than 10(3) cfu/ml. The effect of PPI intake on the relationship between SIBO and IBS was the primary endpoint. RESULTS: Analysis among patients without any history of PPI intake (n = 713) showed that odds ratio (OR) for IBS in the event of SIBO was 5.63 (3.73-8.51, p < 0.0001); this was 4.16 (1.91-9.06) when analysis was done among patients with history of PPI intake (n = 184, p: 0.498 between patients without and with PPI intake). Multiple logistic regression analysis found that factors independently associated with SIBO were age above or equal to 60 years (OR: 2.36), body mass index more than or equal to 22 kg/m(2) (OR: 0.60), presence of IBS (OR: 6.29), type 2 diabetes mellitus (OR: 1.59) and gastritis (OR: 0.47). CONCLUSIONS: The association between IBS and SIBO was completely independent from PPI intake. Although gastritis was protective against SIBO, results show that PPI intake cannot prime SIBO.

Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome.

OBJECTIVE: Breath testing and duodenal culture studies suggest that a significant proportion of irritable bowel syndrome (IBS) patients have small intestinal bacterial overgrowth. In this study, we extended these data through 16S rDNA amplicon sequencing and quantitative PCR (qPCR) analyses of duodenal aspirates from a large cohort of IBS, non-IBS and control subjects. MATERIALS AND METHODS: Consecutive subjects presenting for esophagogastroduodenoscopy only and healthy controls were recruited. Exclusion criteria included recent antibiotic or probiotic use. Following extensive medical work-up, patients were evaluated for symptoms of IBS. DNAs were isolated from duodenal aspirates obtained during endoscopy. Microbial populations in a subset of IBS subjects and controls were compared by 16S profiling. Duodenal microbes were then quantitated in the entire cohort by qPCR and the results compared with quantitative live culture data. RESULTS: A total of 258 subjects were recruited (21 healthy, 163 non-healthy non-IBS, and 74 IBS). 16S profiling in five IBS and five control subjects revealed significantly lower microbial diversity in the duodenum in IBS, with significant alterations in 12 genera (false discovery rate < 0.15), including overrepresentation of Escherichia/Shigella (p = 0.005) and Aeromonas (p = 0.051) and underrepresentation of Acinetobacter (p = 0.024), Citrobacter (p = 0.031) and Microvirgula (p = 0.036). qPCR in all 258 subjects confirmed greater levels of Escherichia coli in IBS and also revealed increases in Klebsiella spp, which correlated strongly with quantitative culture data. CONCLUSIONS: 16S rDNA sequencing confirms microbial overgrowth in the small bowel in IBS, with a concomitant reduction in diversity. qPCR supports alterations in specific microbial populations in IBS.

In vitro activity of rifaximin against isolates from patients with small intestinal bacterial overgrowth.

Rifaximin, a non-absorbable rifamycin derivative, has published clinical efficacy in the alleviation of symptoms in patients with irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) is associated with the pathogenesis of IBS. This study describes for the first time the antimicrobial effect of rifaximin against SIBO micro-organisms from humans. Fluid was aspirated from the third part of the duodenum from 567 consecutive patients; quantitative cultures diagnosed SIBO in 117 patients (20.6%). A total of 170 aerobic micro-organisms were isolated and the in vitro efficacy of rifaximin was studied by (i) minimum inhibitory concentration (MIC) testing by a microdilution technique and (ii) time-kill assays using bile to simulate the small intestinal environment. At a breakpoint of 32 µg/mL, rifaximin inhibited in vitro 85.4% of Escherichia coli, 43.6% of Klebsiella spp., 34.8% of Enterobacter spp., 54.5% of other Enterobacteriaceae spp., 82.6% of non-Enterobacteriaceae Gram-negative spp., 100% of Enterococcus faecalis, 100% of Enterococcus faecium and 100% of Staphylococcus aureus. For the time-kill assays, 11 E. coli, 15 non-E. coli Gram-negative enterobacteria and three E. faecalis isolates were studied. Rifaximin produced a >3 log10 decrease in the starting inoculum against most of the tested isolates at 500 µg/mL after 24h of growth. The results indicate that rifaximin has a potent effect on specific small bowel flora associated with SIBO. This conclusion should be regarded in light of the considerable time-kill effect at concentrations lower than those achieved in the bowel lumen after administration of conventional doses in humans.

The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome.

OBJECTIVES: Many studies have linked irritable bowel syndrome (IBS) with small intestinal bacterial overgrowth (SIBO), although they have done so on a qualitative basis using breath tests even though quantitative cultures are the hallmark of diagnosis. The purpose of this study was to underscore the frequency of SIBO in a large number of Greeks necessitating upper gastrointestinal (GI) tract endoscopy by using quantitative microbiological assessment of the duodenal aspirate. METHODS: Consecutive subjects presenting for upper GI endoscopy were eligible to participate. Quantitative culture of aspirates sampled from the third part of the duodenum during upper GI tract endoscopy was conducted under aerobic conditions. IBS was defined by Rome II criteria. RESULTS: Among 320 subjects enrolled, SIBO was diagnosed in 62 (19.4%); 42 of 62 had IBS (67.7%). SIBO was found in 37.5% of IBS sufferers. SIBO was found in 60% of IBS patients with predominant diarrhea compared with 27.3% without diarrhea (P = 0.004). Escherichia coli, Enterococcus spp and Klebsiella pneumoniae were the most common isolates within patients with SIBO. A step-wise logistic regression analysis revealed that IBS, history of type 2 diabetes mellitus and intake of proton pump inhibitors were independently and positively linked with SIBO; gastritis was protective against SIBO. CONCLUSIONS: Using culture of the small bowel, SIBO by aerobe bacteria is independently linked with IBS. These results reinforce results of clinical trials evidencing a therapeutic role of non-absorbable antibiotics for the management of IBS symptoms.

First diagnosis of inflammatory bowel disease in a 91-year-old man.

Inflammatory bowel diseases (IBDs) are diseases that occur primarily in adolescence and early adult life. A second peak of IBD incidence occurs at the age of 50-80 years, while reports of first diagnosis after the age of 80 years are extremely rare. It is difficult to establish the true incidence of IBD in older patients due to problems of case definition, population, and particularly because it may be confused with other clinical conditions. A 91-year-old man was admitted to the Emergency Department with progressively worsening abdominal pain and 2-4 episodes of bloody diarrhea daily for the last month. Similar symptoms were not reported by the patient or his family during the past. Complete blood count and biochemical tests were normal, while stool examination showed erythrocytes and white blood cells. Pelvic CT showed inflammatory changes and loss of homogeneity in the perirectal fat together with considerable bowel wall thickening of both the rectum and sigmoid. Colonoscopy revealed edema, hyperemia and spontaneous friability, as well as microulcerations of the rectosigmoid mucosa. Tissue biopsies revealed histopathological lesions compatible with IBD. Finally the patient was treated with metronidazole, ciprofloxacin and mesalazine, with clear clinical improvement during the 5th day of treatment, and was finally discharged with almost normal stools. In conclusion, we report the case of first diagnosis of IBD in a 91-year-old man. The prevalence of IBD in patients aged >80 years is difficult to determine. Diagnostic tools are the same as for other age groups, but diagnosis may be difficult because there are a number of clinical conditions that may mimic IBD at this age. The treatment options are those used in younger patients, but special precautions should be taken.

Serum sTREM-1 as a surrogate marker of treatment outcome in patients with peptic ulcer disease.

OBJECTIVE: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is elevated in the gastric juice and in cultures of gastric mucosa of patients with peptic ulcer disease (PUD). Its application as a surrogate marker for the treatment of PUD was assessed. METHODS: From 138 eligible patients, 96 were enrolled; 50 with duodenal ulcer, 29 with gastric ulcer and 17 with chronic gastritis. Patients were endoscoped twice; once before treatment and once after treatment. Biopsy specimens were collected for histopathologic estimation of gastritis. Blood was sampled prior to each endoscopy. Serum was collected and sTREM-1 was measured by an enzyme immunoabsorbent assay ( http://www.clinicaltrials.gov identifier NCT00534443). RESULTS: At the end of treatment sTREM-1 was either: (a) below the limit of detection (this occurred in 62 patients and it was accompanied by lacks signs of residual disease in 58 patients, 93.5%); or (b) above the limit of detection (this occurred in 17 patients and it was accompanied by residual disease in 14 patients, 82.3%) (p < 0.0001). Odds ratio for complete healing of peptic ulcer with sTREM-1 below detection limit was 5.30 (95% CI: 1.89-14.83, p < 0.001) compared to serum sTREM-1 above the limit of detection. CONCLUSIONS: Serum sTREM-1 below detection limit may effectively distinguish patients who successfully completed therapy for PUD from those with residual disease and apply as a surrogate marker.

Evidence for the role of gastric mucosa at the secretion of soluble triggering receptor expressed on myeloid cells (strem-1) in peptic ulcer disease.

AIM: To investigate the role of gastric mucosa at the secretion of sTREM-1 in peptic ulcer. METHODS: Seventy two patients were enrolled; 35 with duodenal, 21 with gastric ulcer and 16 with chronic gastritis. Patients were endoscoped and gastric juice was aspirated. Patients with duodenal and gastric ulcer underwent a second endoscopy post-treatment. Biopsies were incubated in the absence/presence of endotoxins or gastric juice. Supernatants were collected and sTREM-1 and TNFalpha were measured by enzyme immunoabsorbent assays. Scoring of gastritis was performed before and after treatment according to updated Sydney score. RESULTS: Patients with duodenal and gastric ulcer and those with chronic gastritis had similar scores of gastritis. sTREM-1 was higher in supernatants of tissue samples of H pylori-positive than of H pylori-negative patients with gastric ulcer. Median (+/- SE) sTREM-1 was found increased in supernatants of patients with gastric ulcer before treatment (203.21 +/- 88.91 pg/1000 cells) compared to supernatants either from the same patients post-treatment (8.23 +/- 5.79 pg/1000 cells) or from patients with chronic gastritis (6.21 +/- 0.71 pg/1000 cells) (P < 0.001 and < 0.001, respectively). Similar differences for sTREM-1 were recorded among LPS-stimulated tissue samples of patients (P = 0.001). Similar differences were not found for TNFalpha. Positive correlations were found between sTREM-1 of supernatants from patients with both duodenal and gastric ulcer before treatment and the degree of infiltration of neutrophils and monocytes. CONCLUSION: sTREM-1 secreted by the gastric mucosa is an independent mechanism connected to the pathogenesis of peptic ulcer. sTREM-1 was released at the presence of H pylori from the inflamed gastric mucosa in the field of gastric ulcer.

Can soluble triggering receptor expressed on myeloid cells (sTREM-1) be considered an anti-inflammatory mediator in the pathogenesis of peptic ulcer disease?

Soluble triggering receptor expressed on myeloid cells (sTREM-1) is a novel mediator involved in the pathogenesis of peptic ulcer disease. To investigate the potential role of sTREM-1 in the anti-inflammatory response in chronic gastritis, sTREM-1 was compared with other anti-inflammatory mediators of gastritis. Forty patients with dyspepsia were enrolled: 20 with peptic ulcer and 20 controls without any macroscopic abnormalities. All patients were examined by endoscopy; gastric juice was aspirated and biopsy specimens were collected from the antrum and corpus of the stomach. sTREM-1, interleukin (IL)-8, and IL-10 were estimated by enzyme immunoassays. Median sTREM-1 in patient controls and in patients with peptic ulcer disease was 3.91 and 44.27 pg/ml, respectively (P=0.006). Respective values of IL-8 were 1856.97 and 2030.66 pg/ml (P=0.023); those of IL-10 were 16.92 and 18.43 pg/ml (NS). The odds ratio for the presence of peptic ulcer in the event of a concentration of sTREM-1 higher than 15 pg/ml was 23.22 (95% CI, 2.58-208.62; P=0.002). A positive correlation was found between the ratios of IL-8/sTREM-1 and IL-8/IL-10 (r (s), + 0.365; P=0.021). In conclusion, sTREM-1 is an independent factor for the generation of peptic ulcer disease and might behave as an anti-inflammatory mediator in chronic gastritis.

Soluble triggering receptor expressed on myeloid cells (sTREM-1): a new mediator involved in the pathogenesis of peptic ulcer disease.

OBJECTIVES: Triggering receptor expressed on myeloid cells (TREM-1) is a promoter of cytokine production triggered by microbial components. To investigate the significance of its soluble counterpart, sTREM-1, for the pathogenesis of peptic ulcer disease, sTREM-1 was compared with the proinflammatory mediators and the pathology score of gastritis. METHODS: Forty patients with dyspepsia were enrolled: 20 with peptic ulcer and 20 controls without any macroscopic abnormalities. All patients were examined by endoscopy; gastric juice was aspirated and biopsy specimens were collected from the antrum and corpus of the stomach. sTREM-1 was estimated by a hand-made enzyme immunoassay. Interleukin-8 was estimated by enzyme-linked immunosorbent assay and lipid peroxidation, indexed by malondialdehyde, by the thiobarbituric assay, after passage through a high-performance liquid chromatography system. RESULTS: The median (+/-SE) of sTREM-1 of controls and patients with ulcer was 3.91+/-0.57 and 44.27+/-241.55 RU, respectively (P=0.006). The median (+/-SE) of interleukin-8 of controls and patients with ulcer was 1802.97+/-122.10 and 2030.66+/-64.44 pg/ml, respectively (P=0.023). sTREM-1 was positively correlated with the density of neutrophil and mononuclear infiltration scores and the total Sydney score (P=0.029, 0.043 and 0.041, respectively). sTREM-1 was positively correlated with interleukin-8 (P=0.042). CONCLUSIONS: sTREM-1 might be an independent factor involving with the peptic ulcerative inflammatory process that is positively correlated with histopathological abnormalities of gastritis.

Gastric mucosa epithelial cell kinetics are differentiated by anatomic site and Helicobacter pylori infection.

Changes in epithelial cell turnover related to Helicobacter pylori infection may contribute to gastric cancer development. The response of different anatomic sites of the gastric mucosa to H. pylori is not known. We studied apoptosis and cell proliferation at the grater and lesser curvature of the antrum and corpus, the fundus, and the cardia from 9 H. pylori gastritis patients and 11 H. pylori-negative controls with normal histology. Proliferation was highest at the major curve of the antrum and lowest at the fundus, and apoptosis was highest at the cardia and lowest at the major curve of the antrum in both H. pylori gastritis and normal mucosa. Proliferation was significantly higher at all anatomic sites, while apoptosis was significantly lower only at the major and lesser curve of the corpus in H. pylori gastritis compared with normal controls. Our data suggest that gastric mucosa epithelial cell kinetics is differentiated by the anatomic site and H. pylori infection.

Coexistence of Crohn's disease and inflammatory fibroid polyp of the small bowel. Report of a case and review of the literature.

BACKGROUND/AIM: The Authors report a case of a woman aged 35, with concurrent appearance of Crohns disease and Inflammatory Fibroid Polyp of the terminal ileum. CASE REPORT: The combination of the two disorders was clinically manifested as an obstructive ileus. On the operative table, a 4-cm polypoid mass causing intussusception of the bowel was obvious. The resected specimen of the ileum showed profound distention, several ulcerations and fissures. The histological examination confirmed the diagnosis of Crohn's disease coexisting with an Inflammatory Fibroid Polyp. Immunostaining of the lesion for actin showed focal positivity. However, staining for desmin, CD31, S100-protein, PGM-1 CD34, CD117, and bc1-2, was negative. CONCLUSION: Coexistence of Inflammatory Fibroid Polyp with Crohn's disease causing obstructive ileus could be the first manifestation of the disease. The combination of the two disorders corroborates the reparative character of the lesion. Nevertheless, the exact etiopathogenetic relationship between the two entities remains obscure.

Increased fasting serum levels of growth hormone and gastrin in patients with gastric and large bowel cancer.

BACKGROUND: Growth hormone (GH), Insulin-like growth factor-I (somatomedine, IGF-I) and gastrin seem to play a significant role in cell proliferation in mammalian and rat cells. The role of these factors in the etiology of gastric and large bowel cancer has not been completely elucidated. The aim of this study was to concurrently estimate the levels of GH, IGF-I and gastrin in a group of patients with gastric and colorectal cancer and to compare the results with those of a group of normal controls. PATIENTS AND METHODS: In 33 consecutive patients with gastric (16 patients) and large bowel (17 patients) cancer, the serum levels of GH, IGF-I and gastrin were measured by radioimmunoassay. Fifty-four normal people were served as controls. RESULTS: Significantly higher levels of serum GH (3.16 +/- 3.12 ng/ml in gastric cancer patients vs. 3.01 +/- 2.91 ng/ml in colorectal cancer patients vs. 0.69 +/- 1.60 ng/ml in normal controls, adjusted P<0.001) and gastrin (98.2 +/- 87.9 pg/ml in gastric cancer patients vs. 95.3 +/- 85.4 pg/ml in colorectal cancer patients, vs. 47.5 +/- 32.4 pg/ml in normal controls, adjusted P<0.035 and <0.05 respectively) were found in both groups of patients compared with normal controls. The levels of IGF-I in patients with gastric and colorectal cancer although higher compared to normal controls did not reach statistical significance. (98.2 +/- 87.9 pg/ml vs. 95.3 +/- 85.4 vs. 47.5 +/- 32.4 respectively) (adjusted P=0.070). CONCLUSION: It is concluded that in patients with gastric and colorectal cancer a significant increase of serum GH and gastrin can be found. This increase is likely to play a role in gastric and colorectal carcinogenesis.

Serum gastrin levels in patients with inflammatory bowel disease.

The aim of this study was to estimate the levels of serum gastrin in a group of patients with either ulcerative colitis or Crohn's disease and to compare the results with those of a group of normal controls. In 108 consecutive patients with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with indetermined colitis) serum levels of gastrin were measured by radioimmunoassay. One hundred and eight normal people were served as controls. The levels of serum gastrin were significantly elevated in patients with Crohn's disease compared to normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05), irrespectively of the activity of the disease. On the contrary, patients with ulcerative colitis exhibited no significant differences compared to normal controls. Differences between Crohn's disease and ulcerative colitis patients were statistically significant (P<0.001). The rate of infection by Helicobacter pylori in patients with inflammatory bowel disease was statistically significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001). It is concluded that patients with active or inactive Crohn's disease have increased levels of serum gastrin. This may have implications concerning the high incidence of upper GI lesions found in patients with Crohn's disease despite the very low incidence of Helicobacter pylori infection.