Per-Ove Stotzer

Small intestinal bacterial overgrowth in patients with irritable bowel syndrome

Background: Small intestinal bacterial overgrowth (SIBO) has been proposed to be common in irritable bowel syndrome (IBS), with altered small-bowel motility as a possible predisposing factor. Aim: To assess the prevalence of SIBO, by culture of small-bowel aspirate, and its correlation to symptoms and motility in IBS. Methods: 162 patients with IBS who underwent small-bowel manometry and culture of jejunal aspirate were included. Cultures from 26 healthy subjects served as controls. Two definitions of altered flora were used: the standard definition of SIBO (⩾105 colonic bacteria/ml), and mildly increased counts of small-bowel bacteria (⩾95th centile in controls). Results: SIBO (as per standard definition) was found in 4% of both patients and controls. Signs of enteric dysmotility were seen in 86% of patients with SIBO and in 39% of patients without SIBO (p = 0.02). Patients with SIBO had fewer phase III activities (activity fronts) than patients without SIBO (p = 0.08), but otherwise no differences in motility parameters were seen. Mildly increased bacterial counts (⩾5×103/ml) were more common in patients with IBS than in controls (43% vs 12%; p = 0.002), but this was unrelated to small intestinal motility. No correlation between bacterial alterations and symptom pattern was observed. Conclusions: The data do not support an important role for SIBO according to commonly used clinical definitions, in IBS. However, mildly increased counts of small-bowel bacteria seem to be more common in IBS, and needs further investigation. Motility alterations could not reliably predict altered small-bowel bacterial flora.

T-Cell Activation in Patients With Irritable Bowel Syndrome

OBJECTIVES:Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients.METHODS:Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed.RESULTS:IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin β7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1β, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity.CONCLUSIONS:IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.

Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension

OBJECTIVES:Altered small bowel motility and a high prevalence of small intestinal bacterial overgrowth (SIBO) has been observed in patients with liver cirrhosis. Our aim was to explore the relationship between motility abnormalities, portal hypertension, and SIBO.METHODS:Twenty-four patients with liver cirrhosis were included. Twelve had portal hypertension (PH) and 12 had liver cirrhosis (LC) alone. Child-Pugh score was the same in the groups. Antroduodenojejunal pressure recordings were performed, and noninvasive variceal pressure measurements were undertaken. Thirty-two healthy volunteers served as a reference group. Bacterial cultures were obtained from jejunal aspirates.RESULTS:The PH group had a higher proportion of individual pressure waves that were retrograde in the proximal duodenum during phase II (52% vs 13% vs 8% of propagated contractions; p < 0.001) as well as postprandially (49% vs 18% vs 13%; p < 0.01) compared with LC and controls, respectively. Long clusters were more common in PH than in controls (9.1 ± 2.1 vs 4.9 ± 0.8; p < 0.05), and a higher motility index in phase III in the proximal and distal duodenum was seen in the PH as compared with the other groups. The mean variceal pressure was 21 ± 1 mm Hg. Motor abnormalities were not correlated to the level of variceal pressure. Thirty-three percent of the patients in the PH group but none in the LC group had SIBO.CONCLUSIONS:Abnormal small bowel motility and SIBO is common in patients with liver cirrhosis with concomitant portal hypertension. Portal hypertension per se might be significantly related to small bowel abnormalities observed in patients with liver cirrhosis.

Gender differences in gut transit shown with a newly developed radiological procedure.

Background: Gut transit measurements are essential for understanding the pathophysiology of many gastrointestinal disorders. The ideal bowel transit test should be easy to perform, widely accessible, reproducible, non-invasive and inexpensive and the risks should be minimal. These requirements prompted us to develop a procedure for simultaneous measurement of gastric emptying, small-bowel transit and colonic transit at one visit. We assessed the influence of gender, body mass index, age, menopause and smoking on gastrointestinal transit in healthy subjects. Methods: Eighty-three healthy subjects (43 women) were included. Colonic transit was based on 10 radiopaque rings given daily for 6 days with fluoroscopy on day 7. Then, the subjects had a test meal containing 20 radiopaque markers. Using fluoroscopy, gastric emptying and small-bowel transit of the markers were followed until they reached the colon. Results: Gastric emptying, small-bowel transit and colonic transit were significantly slower in female healthy subjects compared to males (2.9 (1.6-4.9) h, median and percentile 10-90, versus 2.4 (0.7-3.7) h, P = 0.005; 4.4 (2.1-11.1) h versus 3.2 (1.5-6.0) h, P = 0.00l; 1.5 (1.0-3.7) days versus 1.3 (0.8-1.9) days P = 0.002), respectively. Small-bowel transit was significantly faster in women with overweight and in postmenopausal women compared to lean and premenopausal women, respectively. Conclusion: This procedure meets most of the requirements of the ideal bowel transit test and is easily performed at one visit. Small-bowel transit as well as gastric emptying and colonic transit were significantly slower for women.

Interdigestive and postprandial motility in small-intestinal bacterial overgrowth.

BACKGROUND Motility disorders are believed to be of major pathogenetic importance in small-intestinal bacterial overgrowth (SIBO). The aim of this study was to investigate interdigestive and postprandial motility in a group of patients with SIBO and to compare the results with those of healthy volunteers. METHODS Twenty healthy subjects and 14 patients with SIBO were included. Exclusion criteria were obvious predisposing conditions. Antroduodenojejunal pressure recording was performed after an overnight fast. After a 5-h interdigestive recording a standard meal was given, and postprandial recording performed for 30 min. RESULTS Significantly fewer patients than healthy subjects had phase-III activity in the antrum (3 of 14 versus 15 of 20; P < 0.01), and more patients lacked phase III completely (5 of 14 versus 0 of 20; P < 0.05). Propagated single contractions in the proximal duodenum during late phase II and postprandially were also significantly reduced (1 (0-5) versus 8 (5-12) per 30 min (median; interquartile range (IQR)) (P < 0.01) and 0.5 (IQR, 0-6.5) versus 8 (IQR, 6-13) per 30 min (P < 0.01), respectively). In the distal part of the duodenum the patients had significantly prolonged duration of phase III (7.8; IQR, 5.6-9.2 versus 5.9; IQR, 4.2-6.6 min) (P < 0.05) and increased motility index of phase III (6685; IQR, 4870-9999 versus 3605; IQR, 2579-5544 mm Hg x min/30 min) (P < 0.05), late phase II (10,285; IQR, 6105-11,384 versus 6650; IQR, 4639-9102) (P < 0.05), and postprandially (12,960; IQR, 8454-18,644 versus 7917; IQR, 6132-10,551) (P < 0.05). Retrograde contractions predominated in the late part of phase III in the proximal duodenum in both groups. The cycle length of the MMC and the number of clustered contractions showed no difference between the two groups. CONCLUSIONS A significant proportion of patients with SIBO, compared with healthy subjects, lack interdigestive phase-III activity, not only in the small intestine but also in the gastric antrum. They also have fewer propagated contractions in the proximal duodenum during interdigestive phase II. On the other hand, the motility index in the distal part of the duodenum was higher in patients with SIBO during phase III, late phase II, and postprandially. The results are compatible with a reduced clearing function in the stomach and proximal duodenum and/or a compensatory increase of motility in the region of the duodenojejunal flexure.

The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis.

BACKGROUND AND AIMS Leukocyte-derived proteins in faeces, especially calprotectin, are increasingly used to assess disease activity in ulcerative colitis. The objectives of the present study were to assess the importance of factors related to the stool sampling procedure. METHODS For 2 days, patients with active ulcerative colitis collected two stool samples at each bowel movement. The time of defecation, consistency and presence of blood were self-recorded in a diary. The variability in the concentrations of calprotectin during the day and between two consecutive days was assessed, as was the stability of calprotectin concentrations in samples stored at room temperature. RESULTS Altogether, 18 patients collected 287 stool samples. The intraclass correlation coefficient in pairs of samples from 132 bowel movements was 0.79 (95% CI 0.48-0.90). The median individual coefficient of variation in samples collected during the same day was 52% (4-178). There was a correlation between the level of calprotectin and the time between bowel movements (r = 0.5; p = 0.013). After 3 days at room temperature the calprotectin concentrations in stool samples were unchanged, but after 7 days a significant (p < 0.01) decrease was found (mean 28%; 95% CI 0.10-0.47). CONCLUSION The present data reveal a great variability in the concentrations of calprotectin in stool samples collected during a single day. Since the levels of calprotectin increased with longer time between the bowel movements, it seems most appropriate to analyse stool from the first bowel movement in the morning. Moreover, storage of stool samples at room temperature for more than 3 days is not advisable.

Etiology of portal hypertension may influence gastrointestinal transit.

Background: Gastrointestinal transit studies have shown contradictory results in patients with portal hypertension. We have studied gastric emptying, small‐bowel transit and colonic transit in patients with portal hypertension. The association between small‐bowel bacterial overgrowth and gastrointestinal transit was assessed. Methods: Sixteen patients (6 females) with portal hypertension and esophageal varices were included. A newly developed radiological procedure was used to measure gastrointestinal transit during one visit. Variceal pressure was measured and culture of small‐bowel aspirate was used to diagnose small‐bowel bacterial overgrowth. The results were compared to results obtained in 83 healthy subjects. Results: Half gastric emptying time in male patients was 3.8 (0.9–5.8) h versus 2.5 (0.4–4.0) h in healthy males (median and percentile 10–90; P < 0.05). Small‐bowel residence time in male patients was 5.9 (2.0–13.7) h versus 3.2 (1.5–6.0) h in healthy males (P < 0.05). Small‐bowel residence time in patients with bacterial overgrowth was significantly longer than in patients without bacterial overgrowth. Small‐bowel residence time was also significantly longer in male patients with alcoholic cirrhosis as compared to male patients with other causes of portal hypertension. Colonic transit in all patients and gastric emptying and small‐bowel transit in female patients were not significantly different from healthy subjects. Conclusion: Etiology of liver disease and gender may influence transit in patients with portal hypertension. Small‐bowel bacterial overgrowth was associated with delayed small‐bowel transit.

Comparison of the 1-Gram 14C-D-Xylose Breath Test and the 50-Gram Hydrogen Glucose Breath Test for Diagnosis of Small Intestinal Bacterial Overgrowth

Background/Aims: Culture of small bowel aspirate is the most direct method and the gold standard for diagnosing small intestinal bacterial overgrowth. However, cultures are cumbersome and fluoroscopy is required for obtaining aspirate. Therefore, different breath tests such as the xylose breath test and the hydrogen breath test have been developed. There is no general agreement as to which test is to be preferred. In the only previous direct comparison between these two tests an advantage for the 1-gram-14C-D-xylose breath test was found. The aim of the study was to compare the 50-gram glucose hydrogen breath test and the 1-gram 14C-D-xylose breath test in relation to results of cultures of small bowel aspirate. Methods: Forty-six consecutive patients, mean age 57 (range 27–87) years, 12 men and 34 women, were included because of suspicion of small intestinal bacterial overgrowth. After small bowel aspiration, all patients received a solution of 1 g xylose, labelled with 50 µg 14C-D-xylose, and 50 g glucose dissolved in 250 ml water. The concentration of breath hydrogen was analyzed every 15 min for 2 h and 14CO2 was analyzed every 30 min for 4 h. A positive hydrogen breath test was defined as a rise in hydrogen concentration of 15 ppm. A positive xylose test was defined as an accumulated dose 4.5% after 4 h. Two definitions for a positive culture were used, either growth of 105 colonic-type bacteria/ml or growth of 105 bacteria/ml of any type. Results: Twenty-four patients had growth of 105 bacteria, of whom 10 had growth of 105 colonic-type bacteria in small bowel aspirate. Twenty-two patients had no significant growth. The hydrogen breath test and the xylose breath test had a sensitivity for growth of 105 bacteria of 58 and 42%, respectively. For growth of 105 colonic-type bacteria the sensitivity was 90% for the hydrogen breath test and 70% for the xylose breath test. The specificity was similar for the two tests. Conclusion: Although no significant difference between the two tests was found, there was a tendency in favor of the 50-gram glucose hydrogen breath test. The simplicity in combination with high sensitivity makes the hydrogen breath test suitable as a screening method to select patients for further investigation.

Accelerated regional bowel transit and overweight shown in idiopathic bile acid malabsorption.

OBJECTIVES:Overweight has recently been shown to accelerate small bowel transit. The role of gut transit and body weight in idiopathic bile acid malabsorption (IBAM) is unclear. We have prospectively studied gastrointestinal transit and body mass index (BMI) in patients with IBAM.METHODS:One hundred and ten patients with chronic diarrhea were prospectively included for transit measurements. All patients underwent a gastroscopy and colonoscopy, 75SeHCAT test for detection of bile acid malabsorption and calculation of BMI. Forty-three patients (15 men) had IBAM. A newly developed radiological procedure was used to measure gastrointestinal transit during one visit. The results were compared to results obtained in 83 healthy subjects.RESULTS:Colonic transit in women with IBAM was 0.8 (0.3–1.5) days versus 1.5 (1.0–3.7) days in healthy women (median and percentile 10 and 90; p < 0.0001). In men with IBAM it was 0.8 (0.1–1.0) days; in healthy men it was 1.3 (0.8–1.9) days, p < 0.0001. Segmental colonic transit was accelerated only in the distal colon in men and women with IBAM compared with healthy subjects. Small bowel transit time in women with IBAM was 1.9 (1.1–3.0) h versus 3.3 (1.5–6.3) h in healthy women, p = 0.0002. In men with IBAM it was 2.1 (1.2–3.2) h and 2.5 (1.4–4.3) h in healthy men (p = 0.04). BMI in patients with IBAM was 27.3 (20.4–33.8) kg/m2 and in healthy subjects it was 23.8 (20.5–26.2) kg/m2, p < 0.0001.CONCLUSION:Accelerated small bowel and distal colonic transit as well as overweight are probably involved in the pathophysiology of IBAM.

Patients with Chronic Renal Failure Have Abnormal Small Intestinal Motility and a High Prevalence of Small Intestinal Bacterial Overgrowth

Background/Aims: Gastrointestinal (GI) symptoms are common among patients with chronic renal failure (CRF). The pathogenesis of these symptoms is probably multifactorial. Our aims were to assess gastric and small intestinal motility and the prevalence of small intestinal bacterial overgrowth (SIBO) in order to clarify possible pathophysiological mechanisms behind these symptoms in CRF patients. Methods: Twenty-two patients with CRF, 12 with GI symptoms and 10 without GI symptoms underwent antroduodenojejunal manometry. All patients with GI symptoms had diarrhea and half of them had abdominal pain, nausea and/or early satiety. Symptoms were unexplained by conventional investigations. Interdigestive motility was recorded for 5 h and postprandially for 1 h. Samples for culture from the small intestine were obtained through the manometry catheter. Results were compared with 34 healthy controls. Results: On manometry, 11 CRF patients demonstrated neuropathic-like abnormalities, with no significant difference between the patients with (7/12) and without (4/10) GI symptoms. SIBO was seen in 8 CRF patients (36%), 3 with and 5 without GI symptoms (p = 0.15). Six of eleven (55%) of the CRF patients with neuropathic-like abnormalities had SIBO, compared to 2/11 (18%) in those without abnormalities on conventional analysis (p = 0.07). The propagation velocity of phase III was significantly faster in CRF patients with GI symptoms compared to CRF patients without symptoms and healthy controls (21.4 (16.4–54.7) vs. 8.1 (4.6–9.6) and 10.8 (7.2–21.6) cm/min, p = 0.007 and p = 0.019, respectively). We found a higher proportion of retrograde pressure waves in late phase II in the proximal duodenum in patients with and without GI symptoms, than in healthy controls (29 (17–38) and 16 (14–42) vs. 8 (0–24)%, p < 0.0001 and p = 0.0005, respectively). The number of long clusters during the fasting recording was higher in both patient groups than in controls (9 (5–21) and 11 (7–15) vs. 4 (2–9)/5, p = 0.046 and p = 0.002, respectively). Conclusion: In the small intestine, abnormal motility and bacterial overgrowth are common in patients with chronic renal failure. These alterations correlate poorly with GI symptoms, but disturbed intestinal motility might explain diarrhea in some of these patients.