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Dysbiosis Contributes to Chronic Constipation Development via Regulation of Serotonin Transporter in the Intestine
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Intestinal microbiota of chronic constipation patients increased SERT levels both in the mice intestinal tissues and the Caco-2 cells. Realtime-PCR results showed SERT mRNA level was up-regulated in intestinal tissues of FMT-C group compared with the FMTH group(A). Intestinal protein levels of SERT in both groups were analyzed by Western blot, using internal control protein β-actin for total protein(B). Proteins were quantified by densitometry using an Imaging processor program(C).Similarly, SERT mRNA levels in Caco2 cells treated with different fecal liquid for 3h(D). Protein levels of SERT in Caco-2 cells treated with different concentration of fecal liquid for 3h analyzed by Western blot(E). Quantitative analysis of the protein levels of SERT treated with different concentration of fecal liquid in Caco-2 cells treated for 3h (F).
NUTRIENT INGESTION LOWERS COLONIC SENSORY THRESHOLDS IN PATIENTS WITH SEVERE CONSTIPATION Jutta Keller, Sebastian Schulz, Viola Andresen, Peter Layer Background: Abdominal pain is frequently aggravated by meals. This is typically the case in irritable bowel syndrome (IBS) and partly explained by decreased sensory thresholds in response nutrient ingestion. However, the influence of nutrient intake on visceral sensitivity has only been studied in healthy volunteers and IBS patients so far and has almost exclusively been examined in the rectum. A single study suggests that feeding decreases colonic sensory thresholds in IBS patients but not in healthy volunteers (Simren et al. Gut 2001). Our aim was to investigate whether nutrient ingestion alters colonic sensory thresholds in patients with severe constipation. Methods: Patients, in whom colectomy was considered because of refractory constipation, underwent combined colonic manometry and barostat investigation for evaluation of phasic and tonic motility as well as colonic sensitivity. Measurements included 1 hour motility recording during the fasting state, ingestion of a 1000 kcal test meal and subsequent recording for another hour. Sensitivity to distension was tested by stepwise increase in the pressure of the barostat balloon before the interdigestive and after the postprandial recording. Results: 89 pts were included during an 8 yrs period (73 women, age: 44.5±16.9 yrs). Nutrient ingestion significantly increased colonic phasic and tonic motility (both p<0.0001). Moreover, all perception thresholds were significantly lower in the fed compared with the fasting state (complete data on sensory thresholds were available in 77 pts, Fig.). There was no association between phasic or tonic motility, on the one hand, and sensory thresholds, on the other hand. Patients who also had motility disturbances of the upper GI tract or anatomical alterations of the colon and anorectum tended to have lower sensory thresholds. Conclusion: Nutrient ingestion markedly decreases colonic sensory thresholds in patients with severe constipation. This effect is apparently independent of alterations of phasic or colonic motility and may contribute to aggravation of abdominal symptoms postprandially.
Intestinal microbiota of chronic constipation patients decreased 5-HT levels in the mice intestinal tissues. ELISA analysis showed a decreased 5-HT level C57BL/6 mice that received the intestinal microbiota of chronic constipation patients (FMT-C) compared with the group that received the intestinal microbiota of healthy controls (FMT-H) (A). Moreover, the 5-HT level was significantly correlated with gastrointestinal transient time (GITT) (B). 5-HT secreted by intestinal chromaffin cells. Chromaffin granules protein A (CgA) is a kind of acid soluble protein which exist in chromaffin cell secretory granules. Paraffin sections of colonic tissues were immunofluorescence stained with primary antibodies against CgA to mark chromaffin cells (Red) and to mark 5-HT (Green) (C). *, P< 0.05, **, P< 0.01.
Effect of feeding on perception and pain thresholds in 77 patients with severe constipation undergoing colonic manometry and barostat investigations
174 175 DYSBIOSIS CONTRIBUTES TO CHRONIC CONSTIPATION DEVELOPMENT VIA REGULATION OF SEROTONIN TRANSPORTER IN THE INTESTINE Xiang Liu, Hailong Cao, Kui Jiang, Bangmao Wang
METHANOGENIC FLORA AND ITS EFFECTS ON REGIONAL AND WHOLE GUT TRANSIT AND SMALL BOWEL PH Jigar Bhagatwala, Amol Sharma, Aarthi Murugappan, Arie Mack, Satish S. Rao
Chronic constipation is a prevalent functional gastrointestinal disorder. Evidence indicates that intestinal dysbiosis can be found in patients with chronic constipation. However, the causal relationship between chronic constipation and intestinal dysbiosis remains poorly understood. Serotonin transporter is a transmembrane transport protein, and can re-uptake excessive 5 - hydroxytryptamine from effective location to terminate its physiological effects and regulate gastrointestinal motility. In this study, fecal microbiota of patients with constipation was transplanted into the pseudo-germfree mouse model (FMT). Intestinal peristalsis of mice were decreasd and their defecation parameters were increased compared to control
Background: Methane (CH4) may have significant effects on gut motility, transit and function. However, the relation between methanogenic flora and both, regional and whole gut transit and small bowel pH has not been systematically assessed. Aim: To investigate regional gut transit and small bowel pH profiles in patients with unexplained GI symptoms and suspected GI dysmotility and those with and without methanogenic flora. Methods: Consecutive patients who underwent both a wireless motility capsule (WMC, SmartPill, Medtronic) test
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AGA Abstracts
AGA Abstracts
group. Analysis of intestinal microbiota indicated that the abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium were decreased after FMT, while the Bacteroides and Akkermansia were increased. Dysfunction of intestinal barrier and the increased serotonin transporter content in colonic tissue we found after transplant, while the content of 5hydroxytryptamine (5-HT) was decreased. In addition, there is a negative correlation between the level of colonic 5-HT and gastrointestinal transit time. Moreover, the Caco-2 cells were stimulated with the fecal solution of constipation patients and healthy human fecal bacteria respectively. We found that the expression of SERT mRNA and SERT protein in Caco-2 cells was significantly higher after being stimulated by fecal bacteria of chronic constipation. Taken together, intestinal dysbiosis may promote the development of chronic constipation by regulating the serotonin transporter.
Intestinal microbiota of chronic constipation patients increased SERT levels both in the mice intestinal tissues and the Caco-2 cells. Realtime-PCR results showed SERT mRNA level was up-regulated in intestinal tissues of FMT-C group compared with the FMTH group(A). Intestinal protein levels of SERT in both groups were analyzed by Western blot, using internal control protein β-actin for total protein(B). Proteins were quantified by densitometry using an Imaging processor program(C).Similarly, SERT mRNA levels in Caco2 cells treated with different fecal liquid for 3h(D). Protein levels of SERT in Caco-2 cells treated with different concentration of fecal liquid for 3h analyzed by Western blot(E). Quantitative analysis of the protein levels of SERT treated with different concentration of fecal liquid in Caco-2 cells treated for 3h (F).
NUTRIENT INGESTION LOWERS COLONIC SENSORY THRESHOLDS IN PATIENTS WITH SEVERE CONSTIPATION Jutta Keller, Sebastian Schulz, Viola Andresen, Peter Layer Background: Abdominal pain is frequently aggravated by meals. This is typically the case in irritable bowel syndrome (IBS) and partly explained by decreased sensory thresholds in response nutrient ingestion. However, the influence of nutrient intake on visceral sensitivity has only been studied in healthy volunteers and IBS patients so far and has almost exclusively been examined in the rectum. A single study suggests that feeding decreases colonic sensory thresholds in IBS patients but not in healthy volunteers (Simren et al. Gut 2001). Our aim was to investigate whether nutrient ingestion alters colonic sensory thresholds in patients with severe constipation. Methods: Patients, in whom colectomy was considered because of refractory constipation, underwent combined colonic manometry and barostat investigation for evaluation of phasic and tonic motility as well as colonic sensitivity. Measurements included 1 hour motility recording during the fasting state, ingestion of a 1000 kcal test meal and subsequent recording for another hour. Sensitivity to distension was tested by stepwise increase in the pressure of the barostat balloon before the interdigestive and after the postprandial recording. Results: 89 pts were included during an 8 yrs period (73 women, age: 44.5±16.9 yrs). Nutrient ingestion significantly increased colonic phasic and tonic motility (both p<0.0001). Moreover, all perception thresholds were significantly lower in the fed compared with the fasting state (complete data on sensory thresholds were available in 77 pts, Fig.). There was no association between phasic or tonic motility, on the one hand, and sensory thresholds, on the other hand. Patients who also had motility disturbances of the upper GI tract or anatomical alterations of the colon and anorectum tended to have lower sensory thresholds. Conclusion: Nutrient ingestion markedly decreases colonic sensory thresholds in patients with severe constipation. This effect is apparently independent of alterations of phasic or colonic motility and may contribute to aggravation of abdominal symptoms postprandially.
Intestinal microbiota of chronic constipation patients decreased 5-HT levels in the mice intestinal tissues. ELISA analysis showed a decreased 5-HT level C57BL/6 mice that received the intestinal microbiota of chronic constipation patients (FMT-C) compared with the group that received the intestinal microbiota of healthy controls (FMT-H) (A). Moreover, the 5-HT level was significantly correlated with gastrointestinal transient time (GITT) (B). 5-HT secreted by intestinal chromaffin cells. Chromaffin granules protein A (CgA) is a kind of acid soluble protein which exist in chromaffin cell secretory granules. Paraffin sections of colonic tissues were immunofluorescence stained with primary antibodies against CgA to mark chromaffin cells (Red) and to mark 5-HT (Green) (C). *, P< 0.05, **, P< 0.01.
Effect of feeding on perception and pain thresholds in 77 patients with severe constipation undergoing colonic manometry and barostat investigations
174 175 DYSBIOSIS CONTRIBUTES TO CHRONIC CONSTIPATION DEVELOPMENT VIA REGULATION OF SEROTONIN TRANSPORTER IN THE INTESTINE Xiang Liu, Hailong Cao, Kui Jiang, Bangmao Wang
METHANOGENIC FLORA AND ITS EFFECTS ON REGIONAL AND WHOLE GUT TRANSIT AND SMALL BOWEL PH Jigar Bhagatwala, Amol Sharma, Aarthi Murugappan, Arie Mack, Satish S. Rao
Chronic constipation is a prevalent functional gastrointestinal disorder. Evidence indicates that intestinal dysbiosis can be found in patients with chronic constipation. However, the causal relationship between chronic constipation and intestinal dysbiosis remains poorly understood. Serotonin transporter is a transmembrane transport protein, and can re-uptake excessive 5 - hydroxytryptamine from effective location to terminate its physiological effects and regulate gastrointestinal motility. In this study, fecal microbiota of patients with constipation was transplanted into the pseudo-germfree mouse model (FMT). Intestinal peristalsis of mice were decreasd and their defecation parameters were increased compared to control
Background: Methane (CH4) may have significant effects on gut motility, transit and function. However, the relation between methanogenic flora and both, regional and whole gut transit and small bowel pH has not been systematically assessed. Aim: To investigate regional gut transit and small bowel pH profiles in patients with unexplained GI symptoms and suspected GI dysmotility and those with and without methanogenic flora. Methods: Consecutive patients who underwent both a wireless motility capsule (WMC, SmartPill, Medtronic) test
S-49
AGA Abstracts
AGA Abstracts
group. Analysis of intestinal microbiota indicated that the abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium were decreased after FMT, while the Bacteroides and Akkermansia were increased. Dysfunction of intestinal barrier and the increased serotonin transporter content in colonic tissue we found after transplant, while the content of 5hydroxytryptamine (5-HT) was decreased. In addition, there is a negative correlation between the level of colonic 5-HT and gastrointestinal transit time. Moreover, the Caco-2 cells were stimulated with the fecal solution of constipation patients and healthy human fecal bacteria respectively. We found that the expression of SERT mRNA and SERT protein in Caco-2 cells was significantly higher after being stimulated by fecal bacteria of chronic constipation. Taken together, intestinal dysbiosis may promote the development of chronic constipation by regulating the serotonin transporter.