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Small Intestinal Bacterial Overgrowth Accelerates Transit in Mice
Su1567 ASSESSMENT OF SMALL BOWEL MOTILITY IN PATIENTS WITH SMALL BOWEL OBSTRUCTION: A NEWLY DEVELOPED MEASUREMENT TECHNIQUE FOR MONITORING SMALL BOWEL MOTILITY BY USING AN ILEUS TUBE Noriaki Manabe, Akihiro Naganawa, Shinji Hosokawa, Kiyoshi Oka, Ken Haruma Background and Aims: Functional assessment of the small bowel is clinically important because it is associated with not only diagnosis, but also treatment strategies, especially for patients with small bowel obstruction (SBO). An ileus tube is clinically applied as a conservative treatment for SBO. Recently, we have newly developed a measurement technique to monitor small bowel motility by using an ileus tube. This study aimed to evaluate differences in small bowel motility in patients with mechanical SBO, those with functional SBO, and healthy controls using this measurement technique. Subjects and Methods: Seven patients with adhesive SBO (one man and 6 women with a mean age of 69.7 years), three with chronic intestinal pseudo-obstruction (one man and 2 women with a mean age of 56.2 years) and 5 healthy controls (5 men; mean age: 29.0 years) were enrolled. A double-balloon ileus tube was inserted through the nose in the supine position until the balloon in front passed across the ligament of Treitz. After acclimation for 60 min, 15 cc of distillated water was injected in the front and back of the balloons of an ileus tube. Each balloon was connected to a pressure sensor and changes in each balloon pressure were monitored for 30 min. For acquisition of data, a data logger was applied (measurement resolution: 0.01 kPa). During measurement, monitoring of breathing by polarized polyvinylidene fluoride film and pulsation by infrared light were also performed. Power spectral analysis of each waveform was then performed with fast Fourier transformation. A power-frequency curve was created for each subject (Figure 1). The motility index was assessed using the 30-min integrated small bowel contraction rate, which was defined as the area under the power vs. the frequency curve. Differences in frequency (cycle/min) and the motility index among the three groups were compared. Results: Measurements of changes in balloon pressure were performed for all subjects. With regard to the frequency of small bowel contraction, large changes in balloon pressure up to a rate of 1 cycle/min and small changes at a rate of 611 cycles/min were detected in the controls (Figure 1). However, the number of large changes in balloon pressure was decreased in patients with adhesive SBO, and both numbers of the two types of changes in balloon pressure were decreased in patients with chronic intestinal pseudo-obstruction. There were differences in frequency and the motility index among the three groups (Table 1). Conclusions: Evaluation of small bowel motility using an ileus tube could be useful for assessing the pathophysiology of SBO. Table 1. Differences in frequency and the motility index among the three groups
Su1565 ARE BREATH TESTS HELPFUL IN PREDICTING THE RESPONSE TO A LOW-FODMAP DIET IN PATIENTS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS? Clive H. Wilder-Smith, Soren S. Olesen, Andrea Materna, Asbjorn M. Drewes Introduction The dietary reduction of poorly fermentable carbohydrates collectively termed FODMAPs (fermentable oligo-, di-, monosaccharides and polyols) is increasingly adopted in patients with functional gastrointestinal disorders (FGID). The role of individual sugar breath tests in the selection of patients for dietary intervention is shifting and is poorly defined. Aims & Methods The associations between hydrogen and methane breath concentrations, specific symptoms provoked during breath testing and global symptom relief with the low-FODMAP diet were examined in successive female and male patients with FGID. All patients included had either lactose or fructose intolerance, defined by a positive symptom index during breath testing. Outcome was assessed using an adequate global symptom relief question after completion of a 6 to 8-week standardized low-FODMAP diet. Predictive associations were assessed by uni- and multivariate analyses. Results Adequate symptom relief was achieved in 81% of the 580 FGID patients of mean (SD) age: 42 (20) years. With univariate analysis, adequate relief with the low-FODMAP diet was positively associated with peak concentrations of breath methane (odds ratio (95% confidence interval): 1.40 (0.98-1.99), p=0.06) and abdominal fullness (1.85 (1.05-3.25), p=0.03) during breath testing in patients with fructose intolerance, and with peak hydrogen (1.06 (1.00-1.13), p=0.038) and peak methane (1.41 (1.06-1.89), p=0.02) concentrations in lactose intolerant patients. There were no significant associations between the areas-under-the-curve or time-concentration profiles of hydrogen or methane and adequate relief in either fructose or lactose intolerant patients. There were no significant predictive associations between the type or the cumulative number of symptoms experienced during breath testing with either fructose or lactose and the response to the diet. Multivariate analysis showed an independent, positive association of peak methane breath concentrations (1.53 (1.02-2.29), p=0.042) with adequate relief in patients with fructose intolerance, but no significant independent response predictors in patients with lactose intolerance. Conclusions Adequate global symptom relief with a lowFODMAP diet is achieved in a large majority of all FGID patients with fructose or lactose intolerance. Peak gas concentrations, but not indicators of gas load, such as time-concentration profiles, or specific test-provoked symptoms, have predictive value regarding dietary responses in patients with FGID and fructose and lactose intolerance. These data suggest intestinal hypersensitivity related to maximum distention or chemical stimulation and factors related to host or microbiome metabolism are relevant in the response to a low-FODMAP diet.
Data are expressed as mean ± standard error. We looked for group differences using oneway ANOVA tests. SBO: small bowel obstruction, CIPO: chronic intestinal pseudo-obstruction, HC: healthy controls.
Su1566 SMALL INTESTINAL BACTERIAL OVERGROWTH ACCELERATES TRANSIT IN MICE Nathaniel Ritz, Derek Lin, Melissa Wilson, Larry L. Barton, Henry C. Lin Background Alternating diarrhea and constipation are characteristic of Irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) has been implicated in IBS (JAMA 2004;292(7):852-8). While constipation may be explained by slowing of intestinal transit by excessive exposure to microbial gases methane (Am J Physiol Gastrointest Liver Physiol 2006;290(6):G1089-95) or hydrogen sulfide (Neurogastroenterol Motil 2016; Doi. 10.1111/ nmo.12907 {Epub}), however, diarrhea remains unexplained. Since bacterial endotoxin was shown to accelerate intestinal transit (J Surg Res 1996;60(2):307-11), we hypothesized that SIBO may accelerate transit. Methods We used raw red kidney bean (RRKB) to induce SIBO (Dig Dis Sci 2010;55(10):2778-84). Six week old female C57BL/6 mice (n = 8 )were fed a
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AGA Abstracts
AGA Abstracts
diet containing 26% RRKB ad libitum for 24 h, fasted for 2 h, then gavaged with a solution (200 µl) containing the fluorescent dye Dextran rhodamine B (6.25 mg/mL) and phosphate buffered saline (1%). Control mice (n = 8) were fed a normal diet before being fasted for 2 h prior to gavage of the same solution. Intestinal transit was measured 20 minutes after gavage by euthanizing the animals, removing the small intestine between the pyloric sphincter and the ileocecal valve, and visualizing the distribution of rhodamine across the intestine using an imaging system (IVIS, Perkin-Elmer). Intestinal transit was analyzed using ImageJ (University of Ghent) and compared by geometric center (GC, 1 = minimal movement and 100 = maximal movement) (Am J Physiol Regul Integr Comp Physiol 2007;292(1):R253-7). DNA was isolated from the small intestine and universal 16S rRNA gene expression was measured by real-time quantitative PCR. Fold change difference relative to the untreated control group was calculated using the 2-∆∆Ct method. Two tailed t-test was used for statistical analysis. Results 1. An increase in the expression of universal 16S rRNA gene was observed in small intestine of mice administered RRKB demonstrating SIBO (1.5+0.2 fold change increase relative to control) (P<0.05). 2. RRKB mice displayed accelerated transit of fluorescent dye (GC=88.3+1.6) compared to control mice (72.2+2.5) (P<0.001). Conclusion SIBO accelerated small intestinal transit in mice, which may explain the diarrhea phenotype observed in IBS. Acknowledgement This work was supported by the Winkler Bacterial Overgrowth Research Fund.
Mean and standard deviation values for the specific physiologic measures
Su1565 ARE BREATH TESTS HELPFUL IN PREDICTING THE RESPONSE TO A LOW-FODMAP DIET IN PATIENTS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS? Clive H. Wilder-Smith, Soren S. Olesen, Andrea Materna, Asbjorn M. Drewes Introduction The dietary reduction of poorly fermentable carbohydrates collectively termed FODMAPs (fermentable oligo-, di-, monosaccharides and polyols) is increasingly adopted in patients with functional gastrointestinal disorders (FGID). The role of individual sugar breath tests in the selection of patients for dietary intervention is shifting and is poorly defined. Aims & Methods The associations between hydrogen and methane breath concentrations, specific symptoms provoked during breath testing and global symptom relief with the low-FODMAP diet were examined in successive female and male patients with FGID. All patients included had either lactose or fructose intolerance, defined by a positive symptom index during breath testing. Outcome was assessed using an adequate global symptom relief question after completion of a 6 to 8-week standardized low-FODMAP diet. Predictive associations were assessed by uni- and multivariate analyses. Results Adequate symptom relief was achieved in 81% of the 580 FGID patients of mean (SD) age: 42 (20) years. With univariate analysis, adequate relief with the low-FODMAP diet was positively associated with peak concentrations of breath methane (odds ratio (95% confidence interval): 1.40 (0.98-1.99), p=0.06) and abdominal fullness (1.85 (1.05-3.25), p=0.03) during breath testing in patients with fructose intolerance, and with peak hydrogen (1.06 (1.00-1.13), p=0.038) and peak methane (1.41 (1.06-1.89), p=0.02) concentrations in lactose intolerant patients. There were no significant associations between the areas-under-the-curve or time-concentration profiles of hydrogen or methane and adequate relief in either fructose or lactose intolerant patients. There were no significant predictive associations between the type or the cumulative number of symptoms experienced during breath testing with either fructose or lactose and the response to the diet. Multivariate analysis showed an independent, positive association of peak methane breath concentrations (1.53 (1.02-2.29), p=0.042) with adequate relief in patients with fructose intolerance, but no significant independent response predictors in patients with lactose intolerance. Conclusions Adequate global symptom relief with a lowFODMAP diet is achieved in a large majority of all FGID patients with fructose or lactose intolerance. Peak gas concentrations, but not indicators of gas load, such as time-concentration profiles, or specific test-provoked symptoms, have predictive value regarding dietary responses in patients with FGID and fructose and lactose intolerance. These data suggest intestinal hypersensitivity related to maximum distention or chemical stimulation and factors related to host or microbiome metabolism are relevant in the response to a low-FODMAP diet.
Data are expressed as mean ± standard error. We looked for group differences using oneway ANOVA tests. SBO: small bowel obstruction, CIPO: chronic intestinal pseudo-obstruction, HC: healthy controls.
Su1566 SMALL INTESTINAL BACTERIAL OVERGROWTH ACCELERATES TRANSIT IN MICE Nathaniel Ritz, Derek Lin, Melissa Wilson, Larry L. Barton, Henry C. Lin Background Alternating diarrhea and constipation are characteristic of Irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) has been implicated in IBS (JAMA 2004;292(7):852-8). While constipation may be explained by slowing of intestinal transit by excessive exposure to microbial gases methane (Am J Physiol Gastrointest Liver Physiol 2006;290(6):G1089-95) or hydrogen sulfide (Neurogastroenterol Motil 2016; Doi. 10.1111/ nmo.12907 {Epub}), however, diarrhea remains unexplained. Since bacterial endotoxin was shown to accelerate intestinal transit (J Surg Res 1996;60(2):307-11), we hypothesized that SIBO may accelerate transit. Methods We used raw red kidney bean (RRKB) to induce SIBO (Dig Dis Sci 2010;55(10):2778-84). Six week old female C57BL/6 mice (n = 8 )were fed a
S-523
AGA Abstracts
AGA Abstracts
diet containing 26% RRKB ad libitum for 24 h, fasted for 2 h, then gavaged with a solution (200 µl) containing the fluorescent dye Dextran rhodamine B (6.25 mg/mL) and phosphate buffered saline (1%). Control mice (n = 8) were fed a normal diet before being fasted for 2 h prior to gavage of the same solution. Intestinal transit was measured 20 minutes after gavage by euthanizing the animals, removing the small intestine between the pyloric sphincter and the ileocecal valve, and visualizing the distribution of rhodamine across the intestine using an imaging system (IVIS, Perkin-Elmer). Intestinal transit was analyzed using ImageJ (University of Ghent) and compared by geometric center (GC, 1 = minimal movement and 100 = maximal movement) (Am J Physiol Regul Integr Comp Physiol 2007;292(1):R253-7). DNA was isolated from the small intestine and universal 16S rRNA gene expression was measured by real-time quantitative PCR. Fold change difference relative to the untreated control group was calculated using the 2-∆∆Ct method. Two tailed t-test was used for statistical analysis. Results 1. An increase in the expression of universal 16S rRNA gene was observed in small intestine of mice administered RRKB demonstrating SIBO (1.5+0.2 fold change increase relative to control) (P<0.05). 2. RRKB mice displayed accelerated transit of fluorescent dye (GC=88.3+1.6) compared to control mice (72.2+2.5) (P<0.001). Conclusion SIBO accelerated small intestinal transit in mice, which may explain the diarrhea phenotype observed in IBS. Acknowledgement This work was supported by the Winkler Bacterial Overgrowth Research Fund.
Mean and standard deviation values for the specific physiologic measures