Enteric neuron density correlates with clinical features of severe gut dysmotility.

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are based mainly on classic qualitative histopathological/immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to quantify the interganglionic distance between neighboring myenteric ganglia immunoreactive for neuron-specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies/ganglion in jejunal specimens of patients with severe GI dysmotility. Jejunal full-thickness biopsies were collected from 32 patients (22 females; 16-77 yr) with well-characterized severe dysmotility and 8 controls (4 females; 47-73 yr). A symptom questionnaire was filled before surgery. Mann-Whitney U test, Kruskal-Wallis coupled with Dunn's posttest and nonparametric linear regression tests were used for analyzing morphometric data and clinical correlations, respectively. Compared with controls, patients with severe dysmotility exhibited a significant increase in myenteric interganglionic distance (P = 0.0005) along with a decrease in the number of myenteric (P < 0.00001) and submucosal (P < 0.0004) neurons. A 50% reduction in the number of submucosal and myenteric neurons correlated with an increased interganglionic distance and severity of dysmotility. Our study proposes a relatively simple tool that can be applied for quantitative evaluation of paraffin sections from patients with severe dysmotility. The finding of an increased interganglionic distance may aid diagnosis and limit the direct quantitative analysis of neurons per ganglion in patients with an interganglionic distance within the control range.NEW & NOTEWORTHY Enteric neuropathies are challenging conditions characterized by a severe impairment of gut physiology, including motility. An accurate, unambiguous assessment of enteric neurons provided by quantitative analysis of routine paraffin sections may help to define neuropathy-related gut dysmotility. We showed that patients with severe gut dysmotility exhibited an increased interganglionic distance associated with a decreased number of myenteric and submucosal neurons, which correlated with symptoms and clinical manifestations of deranged intestinal motility.

Gut epithelial and vascular barrier abnormalities in patients with chronic intestinal pseudo-obstruction.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a rare condition due to severe impairment of gut motility responsible for recurrent subocclusive episodes. Although neuromuscular-glial-ICC abnormalities represent the main pathogenetic mechanism, the pathophysiology of CIPO remains poorly understood. Intestinal epithelial and vascular endothelial barrier (IEVB) abnormalities can contribute to neuroepithelial changes by allowing passage of harmful substances. METHODS: To test retrospectively whether IEVB defects occur in patients with CIPO, we measured the jejunal protein expression of the major tight junction (TJ) components. CIPO patients were subdivided according to gut neuromuscular histopathology: apparently normal (AN); with inflammation (INF); or with degenerative alterations (DEG). The presence of occludin/claudin oligomers (index of TJ assembly), the amount of occludin, claudin-4, and zonula occludens-1 (ZO-1), and the expression of vasoactive intestinal polypeptide (VIP) and glial fibrillary acidic protein (GFAP) immunoreactivities were evaluated on jejunal full-thickness biopsies using Western blot. KEY RESULTS: Oligomers were absent in the 73% of CIPO. Total occludin decreased in CIPO with AN and INF changes. Claudin-4 was upregulated in CIPO with INF and DEG features. ZO-1 and VIP expression decreased selectively in DEG group. GFAP increased in CIPO regardless the histopathological phenotype. CONCLUSIONS & INFERENCES: The absence of oligomers demonstrated in our study suggests that IEBV is altered in CIPO. The mechanism leading to oligomerization is occludin-dependent in AN and INF, whereas is ZO-1-dependent in DEG. Our study provides support to IEVB abnormalities contributing to CIPO clinical and histopathological features.

Effect of prucalopride on intestinal gas tolerance in patients with functional bowel disorders and constipation.

BACKGROUND AND AIM: Patients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT-4 receptors in the gut has both prokinetic and antinociceptive effects. The aim of this study is to determine the effect of prucalopride, a highly selective 5HT-4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation. METHODS: Twenty-four women with functional bowel disorders complaining of constipation were included in the study. Patients were studied twice on separate days in a cross-over design. On each study day, an intestinal gas challenge test was performed. During the five previous days, prucalopride (2 mg/day) or placebo was administered. Abdominal symptoms, stool frequency, and stool consistency were recorded during the treatment period on daily questionnaires. RESULTS: During the gas challenge test, prucalopride did not decrease the volume of gas retained in the subset of patients who had significant gas retention (≥ 200 mL) while on placebo. However, in those patients who had increased symptoms during the gas test (≥ 3 on a 0 to 6 scale) when on placebo, prucalopride did significantly reduce the perception of symptoms (2.3 ± 0.5 mean score vs 3.5 ± 0.3 on placebo; P = 0.045). During the treatment period with prucalopride, patients exhibited an increase in the total number of bowel movements and decreased stool consistency compared with placebo. CONCLUSION: Prucalopride reduces abdominal symptoms without modifying gas retention when patients with functional bowel disorders are challenged with the gas transit and tolerance test. European Clinical Trials Database (EudraCT2011-006354-86).

Effect of selective CCK1 receptor antagonism on accommodation and tolerance of intestinal gas in functional gut disorders.

BACKGROUND: Participants with functional gut disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. To determine the role of cholecystokinin (CCK1 ) receptors on gas transit and tolerance in women with functional gut disorders. METHODS: In 12 healthy women, and 24 women with functional gut disorders (12 dyspepsia and 12 constipation-predominant irritable bowel syndrome) gas was infused into the jejunum at 12 mL/min for 3 h with simultaneous duodenal lipid infusion (intralipid 1 kcal/min), while measuring anal gas evacuation and abdominal symptoms on a 0-6 score scale. Triple-blind paired studies during iv infusion of dexloxiglumide (2.5 mg/kg bolus plus 5 mg/kg h continuous infusion), a selective CCK1 inhibitor, or saline (control) were performed in random order. RESULTS: During saline infusion participants with functional gut disorders developed significantly greater gas retention and abdominal symptoms than healthy subjects (394 ± 40 mL vs 265 ± 35 mL and 2.8 ± 0.3 vs 1.9 ± 0.4 highest abdominal symptom score, respectively; P < 0.05 for both). Dexloxiglumide increased gas retention in both groups (514 ± 35 mL and 439 ± 60 mL, respectively; P = 0.033 vs saline for both); however, despite the larger retention, dexloxiglumide reduced abdominal symptoms (2.3 ± 0.2 score and 0.8 ± 0.3 score, respectively; P = 0.05 vs saline for both). Post-hoc analysis showed that, the decrease in abdominal symptoms was more pronounced in those participants with functional gut disorders with higher basal abdominal symptoms than in the rest (P = 0.037). CONCLUSION: Inhibition of CCK1 receptors by dexloxiglumide increases intestinal gas retention and reduces abdominal symptoms in response to by intestinal gas loads. European Clinical Trials Database (EudraCT 2005-003338-16).

Anal gas evacuation and colonic microbiota in patients with flatulence: effect of diet.

OBJECTIVE: To characterise the influence of diet on abdominal symptoms, anal gas evacuation, intestinal gas distribution and colonic microbiota in patients complaining of flatulence. DESIGN: Patients complaining of flatulence (n=30) and healthy subjects (n=20) were instructed to follow their usual diet for 3 days (basal phase) and to consume a high-flatulogenic diet for another 3 days (challenge phase). RESULTS: During basal phase, patients recorded more abdominal symptoms than healthy subjects in daily questionnaires (5.8±0.3 vs 0.4±0.2 mean discomfort/pain score, respectively; p=<0.0001) and more gas evacuations by an event marker (21.9±2.8 vs 7.4±1.0 daytime evacuations, respectively; p=0.0001), without differences in the volume of gas evacuated after a standard meal (262±22 and 265±25 mL, respectively). On flatulogenic diet, both groups recorded more abdominal symptoms (7.9±0.3 and 2.8±0.4 discomfort/pain, respectively), number of gas evacuations (44.4±5.3 and 21.7±2.9 daytime evacuations, respectively) and had more gas production (656±52 and 673±78 mL, respectively; p<0.05 vs basal diet for all). When challenged with flatulogenic diet, patients' microbiota developed instability in composition, exhibiting variations in the main phyla and reduction of microbial diversity, whereas healthy subjects' microbiota were stable. Taxa from Bacteroides fragilis or Bilophila wadsworthia correlated with number of gas evacuations or volume of gas evacuated, respectively. CONCLUSIONS: Patients complaining of flatulence have a poor tolerance of intestinal gas, which is associated with instability of the microbial ecosystem.

Diseases of the digestive tract: is prevention possible and feasible?

Prevention is and will remain a major goal of medicine and gastroenterology. Economics will have a major influence. Preventive approaches will need to prove a favorable cost-benefit ratio before they are authorized for broad implementation. Personalized medicine is just starting, but undoubtedly it will accelerate, gain relevance and become an integral part of our clinical practice. Physicians in general and gastroenterologists specifically will need to seriously contemplate retraining/refocusing to gain competence in genetic/proteomic evaluation of individuals, or risk a significant degree of obsolescence.

The dysfunctional gut.

After many decades debating whether the clinical manifestations of patients with functional digestive symptoms originate "in their minds" or "in their guts," arguments remain strong on both sides of the controversy. However, advances in understanding of gut physiology and pathophysiology, and persuasive evidence on the bidirectionality of the regulatory traffic between the enteric and central nervous systems, are helping to characterize clinical situations in which we can legitimately speak of gut dysfunction, as opposed to others where symptoms are not associated with apparent or detectable gut disturbances and may truly represent somatization of an affective disorder. In this review, we describe available clinically applicable technology, albeit in specialized clinical research units, that may be used to discern whether or not challenging patients have gut sensory or motor disturbances. The practical yield of applying such methods to diagnostic investigation may be substantial, because it establishes a plausible mechanism of disease that may be used in patient management and patient persuasion, to remove uncertainties and to prevent futile repetition of conventional diagnostic tests. By evolving from symptom analysis to mechanism-based diagnosis, our gastroenterology community may progress toward the goal of delivering the full diagnostic spectrum from altered morphology to disturbed function.

Colonic responses to gas loads in subgroups of patients with abdominal bloating.

OBJECTIVES: We sought to evaluate colonic gas accommodation, ileocecal competence, and colonic clearance in subgroups patients with abdominal bloating. METHODS: Thirty-six patients complaining of abdominal bloating (12 constipation-predominant irritable bowel syndrome (IBS-C), 12 diarrhea-predominant irritable bowel syndrome (IBS-D), and 12 functional bloating) and 18 healthy controls were studied. Abdominal perception and girth were measured during: (i) 1 h continuous infusion of gas at 24 ml/min into the rectum (accommodation period) and (ii) 30 min free rectal gas evacuation (clearance period). In eight patients and eight healthy subjects, the gas infused was labeled with radioactive xenon (74 MBq (133)Xe), and gas distribution was determined by scintigraphy. RESULTS: Colonic gas accommodation produced significantly more abdominal symptoms and distension in patients than in healthy subjects (3.8+/-0.2 vs. 2.4+/-0.3 perception score; P<0.001; 10.9+/-0.6 vs. 8.3+/-0.5 mm girth increment; P=0.009). Scintigraphy showed no differences in colonic gas distribution and no ileal gas reflux, but patients exhibited impaired gas clearance from the proximal colon (63%+/-10% clearance in 30 min vs. 80%+/-2% in health; P=0.042), resulting in more residual gas (506+/-46 vs. 174+/-47 ml; P<0.001), perception (1.9+/-0.2 vs. 1.0+/-0.2 score; P=0.015), and girth increment (4.2+/-0.7 vs. 2.2+/-0.5 mm; P=0.024); IBS-C patients exhibited increased sensation and objective distension, as opposed to sensation only in IBS-D and distension only in functional bloating. CONCLUSIONS: Patients with abdominal bloating have normal colonic accommodation and ileocecal competence but impaired gas clearance from the proximal colon after retrograde infusion, and the consequences of this dysfunction are related to bowel habit.

Lactobacillus casei downregulates commensals' inflammatory signals in Crohn's disease mucosa.

BACKGROUND: The interaction of commensal bacteria with the intestinal immune system is an essential factor in the development of inflammatory bowel disease (IBD). The study of isolated commensal bacteria's effects on the mucosal immune response might be relevant for a better understanding of pathophysiological mechanisms in IBD. METHODS: We investigated the immune responses to signals from the commensal Escherichia coli ATCC 35345 and the probiotic Lactobacillus casei DN-114 001 in Crohn's disease (CD) mucosa. Ileal specimens were obtained during surgery from CD patients. Mucosal explants were incubated with L. casei or its genomic DNA; TNF-alpha, IFN-gamma, IL-2, IL-6, IL-8, and CXCL1 were measured in the supernatant. Second, tissue expression of key proinflammatory cytokines (IL-6, TGF-beta, IL-23p19, IL-12p35, IL-17F), and chemokines (IL-8, CXCL1, CXCL2) was evaluated after incubation with L. casei or E. coli. Finally, combination experiments were carried out by incubating both strains with mucosal explants at different timepoints. RESULTS: Live L. casei significantly decreased secretion of TNF-alpha, IFN-gamma, IL-2, IL-6, IL-8, and CXCL1 by CD mucosa, but the effect was not reproduced by L. casei DNA. Second, live L. casei downregulated expression of IL-8, IL-6, and CXCL1 and did not modify expression of IL-23p19, IL-12p35, and IL-17F. In contrast, E. coli significantly upregulated expression of all these cytokines. Interestingly, combination experiments revealed the ability of L. casei to prevent and counteract the proinflammatory effects of E. coli. CONCLUSIONS: Live L. casei can counteract the proinflammatory effects of E. coli on CD inflamed mucosa by specific downregulation of key proinflammatory mediators.

Intestinal gas and bloating: effect of prokinetic stimulation.

BACKGROUND: It is unknown if abdominal bloating is attributable to excess abdominal gas or improved by a prokinetic agent. AIMS: To assess abdominal gas content in functional abdominal bloating and to ascertain the effect of a prokinetic agent on intestinal gas symptoms in these patients. METHODS: In 20 patients, intra-abdominal gas content and symptoms were quantified before and during treatment with pyridostigmine (30 mg/8 hp. o) in this randomized, placebo-controlled, double-blind study. Daily symptoms were quantified for 5 days before and 10 days during treatment, and abdominal gas volume was quantified by CT imaging before and at the fourth day of treatment. A CT scan was also obtained in 10 healthy subjects. RESULTS: Before treatment, the total volume of intestinal gas was similar in patients (112 +/- 18 mL) and in healthy controls (116 +/- 20 mL). The treatment-induced change in total and regional intestinal gas volume was not significantly different between pyridostigmine (-4 +/- 18 mL; mean +/- SEM) and placebo (0 +/- 15 mL). However, pyridostigmine reduced the severity of bloating from 3.3 +/- 0.3 to 2.6 +/- 0.4 (P < 0.05), whereas placebo did not (3.2 +/- 0.3 vs 3.0 +/- 0.4), although the change did not reach statistical difference across groups. CONCLUSION: In patients complaining of functional bloating, the volume and distribution of intestinal gas, measured on nonselected days, is comparable to asymptomatic subjects. Prokinetic stimulation improves bloating sensation without detectable changes in gas content.

New insight into intestinal motor function via noninvasive endoluminal image analysis.

BACKGROUND & AIMS: Evaluation of small bowel motility by intestinal manometry is invasive and requires expertise for interpretation. Our aim was to use capsule technology for evaluation of small bowel motor function based on a fully computerized image analysis program. METHODS: Thirty-six consecutive patients with severe intestinal motor disorders (19 fulfilling manometric criteria of intestinal dysmotility and 17 not) and 50 healthy subjects received the endoscopic capsule (Pillcam; Given Imaging, Yokneam, Israel). Endoluminal image analysis was performed with a computer vision program specifically developed for the detection of contractile patterns (phasic luminal closure and radial wrinkles by wall texture analysis), noncontractile patterns (tunnel and wall appearance by Laplacian filtering), intestinal content (by color decomposition analysis), and endoluminal motion (by chromatic stability). Automatic classification of normal and abnormal intestinal motility was performed by means of a machine-learning technique. RESULTS: As compared with healthy subjects, patients exhibited less contractile activity (25% less phasic luminal closures, P < .05) and more noncontractile patterns (151% more tunnel pattern, P < .05), static sequences (56% more static images, P < .01), and turbid intestinal content (94% more static turbid images, P < .01). On cross validation, the classifier identified as abnormal all but 1 patient with manometric criteria of dysmotility and as normal all healthy subjects. Out of the 17 patients without manometric criteria of dysmotility, 11 were identified as abnormal and 6 as normal. CONCLUSIONS: Our study shows that endoluminal image analysis, by means of computer vision and machine-learning techniques, constitutes a reliable, noninvasive, and automated diagnostic test of intestinal motor disorders.

Gas distribution within the human gut: effect of meals.

BACKGROUND AND AIMS: Patients frequently complain of gas symptoms precipitated by meals, but the effect of early digestion on intestinal gas content remains unknown. Our aim was to determine the influence of meals on intestinal gas volume and distribution. METHODS: First, we developed a CT image analysis program, based on independent software modules, to measure gas content within the gut. The system was validated in nine healthy subjects by taking helical abdominal CT scans before and after rectal infusion of known volumes of air (100-400 mL). In 15 healthy subjects, intestinal gas distribution was measured in fast and early postcibal CT scans. The postcibal scan was taken 99 +/- 22 minutes after a 597 +/- 57 kcal meal. RESULTS: The volume of gas infused per rectum was detected with an accuracy of 100.4 +/- 3.0%. During fasting, intestinal gas volume was 94 +/- 7 mL (excluding two extreme outliers). After the meal, gas content within the gut increased by 64.7% (up to 149 +/- 21 mL, P < 0.01 vs fast) and the increment occurred in the colon (59 +/- 9 mL precibal vs 121 +/- 20 mL postcibal, P < 0.001), while other gut compartments remained unchanged. CONCLUSION: Ingestion of a meal activated gas metabolism and increased gas content within the gut. The increment occurred early, presumably prior to colonic fermentation of food substrates and was localized in the distal gut, suggesting that gas had a proximal origin and was propelled caudally.

Physical activity and intestinal gas clearance in patients with bloating.

BACKGROUND: Patients complaining of abdominal bloating have impaired tolerance and clearance of intestinal gas loads. Mild exercise enhances intestinal clearance and prevents retention of intestinal gas loads in healthy subjects. Our aim was to evaluate the putative beneficial effects of physical activity in patients with abdominal bloating. METHODS: In eight patients complaining of bloating, seven with irritable bowel syndrome, and one with functional bloating, according to Rome II criteria, a gas mixture was continuously infused (12 mL/min) into the jejunum for 120 min with simultaneous duodenal lipid perfusion (1 kcal/min). Gas evacuation, perception (0-6 scale), and abdominal girth were measured at 15-min intervals. Paired studies were randomly performed in the supine position during intermittent pedaling (5 min with 3-min rest intervals at 40 rpm and 0.15 kp load) versus rest (as control). RESULTS: During rest, a significant proportion of the gas infused was retained in the gut (45 +/- 9%, P < 0.01 vs basal), but retention was significantly lower during exercise (24 +/- 7%, P < 0.05 vs rest). Gas retention during rest was associated with significant abdominal symptoms (3.6 score; P < 0.01 vs basal), and symptoms also improved during exercise (2.8 score, P < 0.05 vs rest). During the test, patients developed abdominal distension, which was related to the volume of gas retained (r = 0.68, P < 0.05). CONCLUSION: Mild physical activity enhances intestinal gas clearance and reduces symptoms in patients complaining of abdominal bloating.

Impaired small bowel gas propulsion in patients with bloating during intestinal lipid infusion.

OBJECTIVE: In healthy individuals, intraluminal lipids delay intestinal gas clearance, and this reflex is exaggerated in patients with irritable bowel syndrome (IBS). Our aim was to determine the site of action of abnormal lipid-induced reflexes in IBS. METHODS: In six patients with (IBS) predominantly complaining of bloating and in six healthy subjects, a mixture of gas (N2, O2, and CO2 in venous proportions to minimize diffusion) was infused (12 mL/min) either into the jejunum or into the ileum for 2 h, with simultaneous perfusion of lipids (0.5 kcal/min) into the proximal duodenum. Rectal gas evacuation was measured by a barostat. Abdominal perception (by a 0-6 scale) and girth changes were measured at 15-min intervals. The effects of jejunal versus ileal gas infusion were compared by paired tests in random order on separate days. RESULTS: IBS patients exhibited significant gas retention during infusion of gas into the jejunum (398 +/- 90 mL vs-210 +/- 105 mL in health, p < 0.05) but not during ileal infusion (-79 +/- 87 mL vs-79 +/- 78 mL in health, NS; p < 0.05 vs jejunal infusion). Gas retention during jejunal gas infusion in IBS patients was associated with significant abdominal distension (11 +/- 3 mm girth increment vs 0 +/- 1 mm during ileal gas infusion and 1 +/- 1 mm in health, p < 0.05 for both) and abdominal symptoms (3.6 +/- 0.6 score vs 2.6 +/- 0.7 score during ileal gas infusion and 1.6 +/- 0.5 score in health, p < 0.05 for both). CONCLUSIONS: In IBS patients intraluminal lipids impair intestinal gas clearance because of upregulated reflex inhibition of small bowel transit, without appreciable colonic effects.

Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease.

Apoptosis of active T lymphocytes constitutes a major control mechanism of immune homeostasis and tolerance. In Crohn's disease, abnormal activation of mucosal T lymphocytes against enteric bacteria is the key event triggering intestinal inflammation. Resistance of lymphocytes to apoptosis has been proposed as the pathogenetic defect. We examined the influence of bacteria-mucosa interactions on apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from 12 patients with Crohn's disease. Mucosal explants from each specimen were cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN-114 001, or no bacteria. Cytokine release was measured in supernatant, and mononuclear cells were isolated for phenotypic characterization and Bcl-2 family protein expression. Coculture of inflamed tissue with L. casei significantly reduced the release of interleukin (IL)-6 and tumor necrosis factor alpha (P < 0.05). In addition, coculture with L. casei significantly reduced the number of T cells displaying the IL-2 receptor in the lamina propria. Expression of the antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no significant effect. In conclusion, L. casei reduces the number of activated T lymphocytes in the lamina propria of Crohn's disease mucosa. A balanced, local microecology may restore immune homeostasis.

Origin of gas retention and symptoms in patients with bloating.

BACKGROUND & AIMS: Patients reporting abdominal bloating exhibit impaired tolerance to intestinal gas loads. The aim of this study was to identify the gut compartment responsible for gas retention. METHODS: In 30 patients predominantly reporting abdominal bloating (24 with irritable bowel syndrome and 6 with functional bloating) and 22 healthy subjects, gas (nitrogen, carbon dioxide, and oxygen) was infused into the intestine for 2 hours while measuring rectal gas outflow. First, in 12 patients and 10 healthy subjects, gas transit (24 mL/min jejunal infusion labeled with 74 MBq bolus of 133 Xe) was measured by scintigraphy. Second, in groups of patients and healthy subjects, the effects of gas infusion (12 mL/min) in the jejunum versus ileum, jejunum versus cecum, and jejunum versus sham infusion (n=6 each) were compared by paired tests. RESULTS: In patients, total gut transit of gas was delayed (50% clearance time, 33 +/- 4 min vs 23 +/- 4 min in healthy subjects; P <.05) owing to impaired small bowel transit (50% clearance time, 20 +/- 2 min vs 12 +/- 3 min in healthy subjects; P <.05), whereas colonic transit was normal (50% clearance time, 13 +/- 2 min vs 11 +/- 2 min in healthy subjects; not significant). Furthermore, jejunal gas infusion in patients was associated with gas retention (329 +/- 81 mL vs 88 +/- 79 mL in healthy subjects; P <.05), whereas direct ileal or colonic infusion was not (61 +/- 103 mL and -143 +/- 87 mL retention, respectively). CONCLUSIONS: In patients reporting bloating, the small bowel is the gut region responsible for ineffective gas propulsion.

Effects of physical activity on intestinal gas transit and evacuation in healthy subjects.

PURPOSE: To determine the effects of mild physical activity on intestinal gas transit and clearance. METHODS: In 8 healthy adults, a gas mixture was infused continuously into the jejunum (12 mL/min) for 120 minutes with simultaneous duodenal lipid perfusion (1 kcal/min). Gas evacuation, perception of abdominal sensations (on a scale of 0 [none] to 6 [pain]), and abdominal girth were measured at 15-minute intervals during rest and intermittent pedalling, with subjects in a supine position. RESULTS: Mean (+/- SD) intestinal gas retention was lower during exercise than at rest (-84 +/- 303 mL vs. 143 +/- 219 mL, P <0.05). Gas retention during rest was associated with significant abdominal distension (8 +/- 6 mm, P <0.01 vs. basal), which was decreased with exercise (3 +/- 7 mm, P <0.05 vs. rest). The gas challenge test was well tolerated both during exercise and rest (perception score: 0.6 +/- 0.5 vs. 0.9 +/- 0.4, P = 0.25). CONCLUSION: In healthy subjects, gut transit of intraluminal gas is enhanced by mild physical activity.

Reflex control of intestinal gas dynamics and tolerance in humans.

Intestinal transit of gas is normally adapted to the luminal gas load, but in some patients impaired transit may lead to gas retention and symptoms. We hypothesized that intestinal gas transit is regulated by reflex mechanisms released by segmental distension at various gut levels. In 24 healthy subjects, we measured gas evacuation and perception of jejunal gas infusion (12 ml/min) during simultaneous infusion of duodenal lipids mimicking the postprandial caloric load (Intralipid, 1 kcal/min). We evaluated the effects of proximal (duodenal) distension (n = 8), distal (rectal) distension (n = 8), and sham distension, as control (n = 8). Duodenal lipid infusion produced gas retention (366 +/- 106 ml) with low abdominal perception (1.5 +/- 0.8 score). Distension of either the duodenum or rectum during lipid infusion expedited gas transit and prevented retention (-120 +/- 164 and -124 +/- 162 ml retention, respectively; P < 0.05 vs. control). However, the tolerance to the intestinal gas load differed markedly, depending on the site of distension; perception remained low during rectal distension (2.6 +/- 0.7 score; not significant vs. control) but increased during duodenal distension (4.4 +/- 0.7 score; P < 0.05 vs. control). We conclude that focal gut distension, either at proximal or distal sites, accelerates gas transit, but the symptomatic response depends on the site of stimulation.

Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa.

OBJECTIVE: The human intestine harbors a complex microbial ecosystem, and the mucosa is the interface between the immune system and the luminal environment. The aim of this study was to elucidate whether host-bacteria interactions influence mucosal cytokine production. METHODS: Macroscopically normal colonic specimens were obtained at surgery from eight patients with neoplasm, and inflamed ileal specimens were obtained from two patients with Crohn's disease. Mucosal explants were cultured for 24 h with either nonpathogenic Escherichia coli ECOR-26, Lactobacillus casei DN-114 001, L. casei DN-114 056, L. casei ATCC-334, or Lactobacillus bulgaricus LB-10. Each study included blank wells with no bacteria. Tissue and bacteria viability were confirmed by LDH release and culture. Concentration of tumor necrosis factor (TNF)alpha, transforming growth factor beta1, interleukin (IL)-8, and IL-10 was measured in supernatants. In parallel experiments, neutralizing anti-TNFalpha antibody was added to the culture. RESULTS: Co-culture of mucosa with bacteria did not modify LDH release. Co-culture with L. casei strains significantly reduced TNFalpha release, whereas E. coli increased it. These effects were observed both in normal and inflamed mucosa. In combination studies, L. casei DN-114 001 prevented TNFalpha stimulation by E. coli. L. casei DN-114 001 also reduced IL-8 release via a TNFalpha-independent pathway. L. casei DN-114 056 or E. coli increased IL-10 release in the presence of neutralizing anti-TNFalpha. CONCLUSIONS: Nonpathogenic bacteria interact with human intestinal mucosa and can induce changes in cytokine production that are strain specific.

Gut flora in health and disease.

The human gut is the natural habitat for a large and dynamic bacterial community, but a substantial part of these bacterial populations are still to be described. However, the relevance and effect of resident bacteria on a host's physiology and pathology has been well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonised host against invasion by alien microbes. Gut flora might also be an essential factor in certain pathological disorders, including multisystem organ failure, colon cancer, and inflammatory bowel diseases. Nevertheless, bacteria are also useful in promotion of human health. Probiotics and prebiotics are known to have a role in prevention or treatment of some diseases.