Abnormal colonic fermentation in irritable bowel syndrome

BACKGROUND: The cause of irritable bowel syndrome (IBS) is unknown. It may follow gastroenteritis and be associated with an abnormal gut flora and with food intolerance. Our study was designed to assess whether these factors were associated with colonic malfermentation. METHODS: We carried out a crossover controlled trial of a standard diet and an exclusion diet matched for macronutrients in six female IBS patients and six female controls. During the final 72 h on each diet, faecal excretion of fat, nitrogen, starch, and non-starch polysaccharide NSP was measured, and total excretion of hydrogen and methane collected over 24 h in a purpose-built 1.4 m3 whole-body calorimeter. Breath hydrogen and methane excretion were then measured for 3 h after 20 g oral lactulose. FINDINGS: The maximum rate of gas excretion was significantly greater in patients than in controls (2.4 mL/min IQR 1.7-2.6 vs 0.6, 0.4-1.1). Although total gas production in patients was not greater than in controls (median 527 mL/24 h IQR 387-660 vs 412, 234-507), hydrogen production was higher (332, 318-478 vs 162, 126-217, p=0.009). In patients, the exclusion diet reduced symptoms and produced a fall in maximum gas excretion (0.5 mL/min IQR 0.3-0.7). After lactulose, breath hydrogen was greater on the standard than on the exclusion diet. INTERPRETATION: Colonic-gas production, particularly of hydrogen, is greater in patients with IBS than in controls, and both symptoms and gas production are reduced by an exclusion diet. This reduction may be associated with alterations in the activity of hydrogen-consuming bacteria. Fermentation may be an important factor in the pathogenesis of IBS.     

In vitro studies on transport and metabolism of short-chain fatty acids in pig hindgut

An analytical method based on alkaline freeze drying, ultracentrifugation, and quantitative gas chromatography was established to differentiate between mucosal uptake, tissue accumulation, and serosal release of SCFA in pig hindgut. It was shown that serosal release of SCFA was substantially lower than mucosal uptake and tissue accumulation, indicating substantial degradation and/or metabolism during transepithelial movement.     

Fecal characteristics contrasted in the irritable bowel syndrome and diverticular disease

A comparison has been made of the fecal characteristics in controls and patients with the irritable bowel syndrome and diverticular disease. No detectable difference was found in the fecal wet weight, dry weight, or total bile acid excretion in the four groups. A significant increase in the percentage of the water content of the stool was seen in the idiopathic diarrhea group with irritable bowel syndrome. Significantly less magnesium, potassium, and calcium was found in the stools of patients with diverticular disease and a similar trend was noted in patients with the spastic colon. These changes did not relate to the age of the patients. This suggests a common etiology for these disorders. The presence of increased water and primary bile acids in the feces of patients with idiopathic diarrhea suggests that this is a separate entity.     

Spectral analysis of heart rate variability in patients with irritable bowel syndrome

BACKGROUND: Autonomic dysfunction, both adrenergic and cholinergic, has been associated with the irritable bowel syndrome (IBS). The accuracy of the methods in use, however, has been limited by the need for active co-operation by the patients, with consequent difficulties in standardization. The aim of this study was to investigate the function of the autonomic nervous system in patients with IBS by using spectral analysis of the heart rate variability, an accurate method depending very little on patient cooperation. METHODS: Eighteen patients with IBS were compared with 36 sex- and age-matched controls. Spectral analysis of heart rate variability was performed to quantify sympathetic and parasympathetic nerve activity. RESULTS: The patients with IBS had significantly higher sympathetic activity than controls (P = 0.005). There was no significant (P = 0.308) increase in parasympathetic activity. There were no significant differences in heart rate or blood pressure between the patients and controls. CONCLUSION: Spectral analysis of heart rate variability has been used to assess the function of the autonomic nervous system in patients with IBS. IBS patients have significantly increased symphathetic activity, whereas parasympathetic activity does not differ from that of controls.     

Symptom relief with amitriptyline in the irritable bowel syndrome

An assay was developed for the specific detection of Escherichia coli O157 using PCR, because O serological cross-reactivities have been reported between E. coli O157 and some E. coli, other bacterial species. PCR amplification of E. coli O157 rfbE (Ec O157:H7) gene that is necessary for the expression of the O157 antigen, was performed for the identification of E. coli O157. All Shiga toxin-producing Escherichia coli (STEC) O157:H7 and O157:H, non-STEC O157 strains were positive, and other non-O157 E. coli strains were negative by PCR. All tested strains of other bacterial species, like Salmonella O30 and Citrobacter freundii which gave positive results with O157 detection kits, were negative by PCR. It is recommended that PCR amplification of O157 rfbE gene is one of the most specific method for E. coli O157 identification.     

Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment

BACKGROUND: Antibiotic-associated diarrhoea (AAD) may range from mild disturbances to severe pseudomembranous colitis. Many antibiotics affect several intestinal microflora-associated characteristics, such as short-chain fatty acid (SCFA) pattern. In the present study we investigated SCFAs in 31 patients on admittance to the hospital for severe AAD. Nine patients were followed up more extensively after they had received an enema containing faecal microflora from a healthy person on a Western diet. METHODS: Faecal SCFAs were determined by gas chromatography. The enema was characterized before use. RESULTS: AAD patients showed significant disturbances in faecal SCFA pattern. Clinically, most enema-treated patients recovered within days and had no relapses within 18 months. CONCLUSIONS: Intestinal microflora showed great disturbances, and the amounts of SCFAs were reduced, although the diarrhoea was not related to total amount SCFAs. Administration of a faecal enema resulted in the clinical recovery of most patients with severe diarrhoea within 4 days.     

Sugar composition of dietary fibre and short-chain fatty acid production during in vitro fermentation by human bacteria

The aim of the present study was to assess the relationship between the disappearance of dietary fibre sugars and the production of individual short-chain fatty acids (SCFA). The bacterial degradation of five dietary fibres whose sugars were quantified was investigated in vitro using a human faecal inoculum. Involvement of the main fibre sugars in SCFA production was evaluated by a stepwise multiple linear regression. The results show first that the nature and chiefly the associations between the fibre sugars were key variables in the fermentability. Second, the nature and the amounts of SCFA produced were closely related to the in vitro fermentation of the main sugars available: uronic acids seemed to be principally involved in the production of acetic acid whereas the production of propionic acid could be promoted by the fermentation of glucose and, to a lesser extent, by that of xylose and arabinose. Xylose tended to have a greater impact than uronic acids and glucose on the production of butyric acid. Thus, it would be possible to predict which SCFA could be specifically produced during the fermentation of a fibre, as far as the chemical composition and structure of this fibre are known.     

Use of a novel electronic data collection system in multicenter studies of irritable bowel syndrome

To evaluate whether atherosclerosis may be associated with altered leucocyte rheology, we assessed leucocyte count (by Coulter counter), aggregation (by means of the leukergy test) and expression of adhesion molecules integrin LFA-1 and CD 44 (by means of immunofluorescence staining and flow cytometry) in 9 patients with carotid plus lower limb artery atherosclerosis (group A), 14 patients with carotid atherosclerosis only (group B) and 23 controls without atherosclerosis (group C). The level of LFA-1 (calculated as mean fluorescence channels-MFCs) on neutrophils, lymphocytes and monocytes was significantly higher (p < 0.05) in group A and B patients than in controls (group A-mean +/- SE: 383.77 +/- 9.42 vs 295.45 +/- 5.76; 474.22 +/- 8.86 vs 388.35 +/- 7.84; 457.66 +/- 12.03 vs 396.25 +/- 4.37. Group B: 322.42 +/- 6.36 vs 295.45 +/- 5.76; 421.42 +/- 7.21 vs 388.35 +/- 7.84; 415.71 +/- 7.73 vs 396.25 +/- 4.37, respectively); furthermore, the MFC of LFA-1 on neutrophils was significantly different (p < 0.05) between group A and B patients. The percentage of aggregated leucocytes was significantly higher (p < 0.05) in group A patients (4.46 +/- 1.07) than those in groups B (1.75 +/- 0.38) and C (1.43 +/- 0.25), whereas no significant difference was detected between groups B and C. Leucocyte number and expression of CD44 were not significantly different among the 3 groups. In conclusion, changes in leucocyte rheology are present in patients with atherosclerosis and may contribute to chronic ischaemia.     

Increased urine catecholamines and cortisol in women with irritable bowel syndrome

OBJECTIVES: There are few data on the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis in individuals with chronic GI symptoms. The current study was designed to describe and compare urine catecholamine (norepinephrine, epinephrine) and cortisol levels in women diagnosed with irritable bowel syndrome (IBS-patients), women who report similar symptom levels but had not sought health care services (IBS-nonpatients; IBS-NP), and asymptomatic (control) women. METHODS: Seventy-three women (24 IBS; 24 IBS-NP; 25 controls) were interviewed for demographic, GI, gynecological, and psychological data and then followed for two menstrual cycles with a daily health diary. Urine samples were obtained in the evening and morning at specific phases across two menstrual cycles. RESULTS: Women in the IBS group had significantly higher PM and AM urine norepinephrine levels. Urine epinephrine and cortisol levels were also generally higher in women with IBS. Differences in neuroendocrine indicators of arousal were not accounted for by differences in demographic variables, lifestyle characteristics, menstrual distress, or average daily measures of anxiety or depression. CONCLUSIONS: Increases in indicators of sympathetic nervous system activation in women seeking health care for IBS may reflect greater symptom distress or may contribute to increased symptom distress.     

Extracellular pH regulation in microdomains of colonic crypts: effects of short-chain fatty acids

It has been suggested that transepithelial gradients of short-chain fatty acids (SCFAs; the major anions in the colonic lumen) generate pH gradients across the colonic epithelium. Quantitative confocal microscopy was used to study extracellular pH in mouse distal colon with intact epithelial architecture, by superfusing tissue with carboxy SNARF-1 (a pH-sensitive fluorescent dye). Results demonstrate extracellular pH regulation in two separate microdomains surrounding colonic crypts: the crypt lumen and the subepithelial tissue adjacent to crypt colonocytes. Apical superfusion with (i) a poorly metabolized SCFA (isobutyrate), (ii) an avidly metabolized SCFA (n-butyrate), or (iii) a physiologic mixture of acetate/propionate/n-butyrate produced similar results: alkalinization of the crypt lumen and acidification of subepithelial tissue. Effects were (i) dependent on the presence and orientation of a transepithelial SCFA gradient, (ii) not observed with gluconate substitution, and (iii) required activation of sustained vectorial acid/base transport by SCFAs. Results suggest that the crypt lumen functions as a pH microdomain due to slow mixing with bulk superfusates and that crypts contribute significant buffering capacity to the lumen. In conclusion, physiologic SCFA gradients cause polarized extracellular pH regulation because epithelial architecture and vectorial transport synergize to establish regulated microenvironments.     

Evidence for autonomic nervous system imbalance in women with irritable bowel syndrome

Autonomic nervous system function was assessed in women with and without irritable bowel syndrome using frequency domain measures of heart rate variability. Women were interviewed and placed into the irritable bowel syndrome (N = 25) group based on history of diagnosis and self-report of current gastrointestinal symptoms. Women in the control group denied a history of chronic gastrointestinal symptoms (N = 15). Women were followed for one menstrual cycle with a symptom diary, and during mid-luteal phase they wore a Holter 24-hr electrocardiograph monitor. Women with irritable bowel syndrome demonstrated significantly lower vagal tone as measured by the high frequency spectrum relative to control women. In addition, women with irritable bowel syndrome had a flattened 24-hr pattern of heart rate variability, with significantly lower levels of vagal tone during sleep. These results suggest that systemic sympathovagal balance may be shifted in a subset of women with irritable bowel syndrome.     

Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial

CONTEXT: Irritable bowel syndrome (IBS) is a common functional bowel disorder for which there is no reliable medical treatment. OBJECTIVE: To determine whether Chinese herbal medicine (CHM) is of any benefit in the treatment of IBS. DESIGN: Randomized, double-blind, placebo-controlled trial conducted during 1996 through 1997. SETTING: Patients were recruited through 2 teaching hospitals and 5 private practices of gastroenterologists, and received CHM in 3 Chinese herbal clinics. PATIENTS: A total of 116 patients who fulfilled the Rome criteria, an established standard for diagnosis of IBS. INTERVENTION: Patients were randomly allocated to 1 of 3 treatment groups: individualized Chinese herbal formulations (n = 38), a standard Chinese herbal formulation (n = 43), or placebo (n = 35). Patients received 5 capsules 3 times daily for 16 weeks and were evaluated regularly by a traditional Chinese herbalist and by a gastroenterologist. Patients, gastroenterologists, and herbalists were all blinded to treatment group. MAIN OUTCOME MEASURES: Change in total bowel symptom scale scores and global improvement assessed by patients and gastroenterologists and change in the degree of interference in life caused by IBS symptoms assessed by patients. RESULTS: Compared with patients in the placebo group, patients in the active treatment groups (standard and individualized CHM) had significant improvement in bowel symptom scores as rated by patients (P=.03) and by gastroenterologists (P=.001), and significant global improvement as rated by patients (P=.007) and by gastroenterologists (P=.002). Patients reported that treatment significantly reduced the degree of interference with life caused by IBS symptoms (P=.03). Chinese herbal formulations individually tailored to the patient proved no more effective than standard CHM treatment. On follow-up 14 weeks after completion of treatment, only the individualized CHM treatment group maintained improvement. CONCLUSION: Chinese herbal formulations appear to offer improvement in symptoms for some patients with IBS.     

Vegetable fiber fermentation by human fecal bacteria: cell wall polysaccharide disappearance and short-chain fatty acid production during in vitro fermentation and water-holding capacity of unfermented residues

Dietary fiber from eight vegetables (broccoli, carrot, cauliflower, celery, cucumber, lettuce, onion and radish) was analyzed for chemical composition and potential in vitro fermentation by human fecal bacteria. Total dietary fiber concentration of substrates ranged from 34.9 (broccoli) to 5.8 (cucumber) g/kg edible matter. Substrate fiber fractions were composed primarily of pectic substances and cellulose with smaller concentrations of hemicelluloses and lignin. Total dietary fiber residues isolated from substrates were fermented in vitro for 24 h with fecal bacteria obtained from each of three human volunteers. Substrate dry matter disappearance during fermentation was highest for carrot (63.7%) and lowest for cucumber (49.4%). Averaged across all substrates, disappearances of arabinose, galactose, glucose, mannose, xylose and uronic acids during fermentation were 96, 90, 54, 68, 51 and 97%, respectively. Short-chain fatty acid (SCFA) production during substrate fermentation averaged 10.5 mmol SCFA/g dry matter fermented. Averaged across all substrates, production of the major SCFA, acetate, propionate and butyrate, occurred in the molar ratio 76:14:10. Potential water-holding capacity of substrates was not influenced by fiber source and averaged 2.04 g H2O/g original substrate dry matter. Extent of substrate fermentation, SCFA production and substrate potential water-holding capacity were significantly different among inoculum donors, indicating that considerable inter-individual variation exists in the potential in vivo fermentation of vegetable fiber.     

Three cases of irritable bowel syndrome treated with stellate ganglion block]

We examined three patients with irritable bowel syndrome (IBS) who did not respond to drug therapy and who were treated by stellate ganglion block (SGB) alone. The clinical symptoms improved by the SGB in all these three patients. There was no recurrence. The pathophysiological mechanism of this disease and the therapeutic efficacy of SGB should be elucidated with respect to the autonomic nervous, endocrine and immune systems. These results suggest that SGB therapy is effective for IBS, a typical psychosomatic disease.     

Fecal bile acids and neutral sterols in patients with familial polyposis

Fecal neutral steroids and bile acids were measured in patients with familial polyposis, family controls who are immediate relatives of patients, and controls other than relatives. All subjects were consuming a mixed Western diet at the time of collection of stool specimens. Although the total fecal neutral sterol concentrations were not different between the groups, the patients with familial polyposis excreted a high amount of cholesterol and low levels of coprostanol and coprostanone compared with other groups. Patients with familial polyposis excreted levels of total bile acids in their feces comparable to those excreted by controls; lithocholic acid excretion was decreased in patients with familial polyposis. These findings suggest that analysis of stools for cholesterol and its metabolites be useful in screening the siblings of polyposis families for latent disease.     

Toward a biobehavioral model of visceral hypersensitivity in irritable bowel syndrome

A review of records at a large urban methadone clinic revealed a substantial group of patients with treatment tenures of at least 6 months whose urinalysis results indicated continued regular use of opiates. In an attempt to characterize these "nonresponsive" patients and to identify their specific treatment needs, we compared them to a group of patients with comparable treatment tenures but whose urinalysis results indicated little or no recent illicit opiate use. Contrary to expectations, opiate use itself was virtually the only feature that clearly distinguished the two groups. "Responders" and "nonresponders" did not differ significantly on measures of psychosocial problem severity in any other area, nor did they differ in their treatment service utilization. Moreover, examination of admission data indicated that the two groups showed similar rates of improvement in the severity of their psychosocial problems in all seven measured areas. The implications of these results for treatment and clinic administration are discussed.     

Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome

The present study adopted a prospective design to explore relationships among various types of social support and depression. Four types of social support, namely network support, instrumental enacted support, socio-emotional enacted support, and perceived support, were assessed in a sample of Chinese adolescents. Results revealed that perceived support was related to a reduction of subsequent depression for both male and female adolescents. In addition, instrumental enacted support was a significant predictor of subsequent depression for male adolescents, whereas socioemotional enacted support was a significant predictor of subsequent depression for female adolescents. Functional differences in the types of social support for Chinese male and female adolescents, as well as implications for clinical intervention, are discussed.     

Effect of short-chain fatty acids on cell volume and intracellular pH in rat distal colon

Superfusion of isolated crypts from the rat colon with sodium-butyrate-containing solutions induced an increase in the crypt diameter indicating a swelling of the crypt cells. The response to butyrate (50 mmol l-1) was not uniform along the crypt axis, the most pronounced swelling being observed in the upper third of the crypt. The butyrate effect was concentration-dependent and was completely suppressed by amiloride, suggesting that it is caused by activation of the Na+/H+ exchanger. Acetate, propionate and isobutyrate had a similar action. In HEPES-buffered solution the butyrate-induced change in cell volume was monophasic, i. e. only a swelling took place, whereas in HCO3- buffer it was biphasic, i. e. swelling was followed by a regulatory volume decrease. This decrease was suppressed by K+ and Cl- channel blockers as well as inhibitors of leukotriene synthesis. Measurements of intracellular pH with the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) revealed that butyrate induced an acidification of the cell, which was stronger in HEPES than in HCO3- buffer. Estimation of Na+/H+ exchange activity, tested as recovery of intracellular pH from an acid load via an NH4Cl prepulse, revealed a much lower Na+/H+ exchange activity in the fundus region compared to the upper third of the crypt. The smaller volume response evoked by butyrate in the fundus region probably reflects the smaller Na+/H+ activity compared to the more differentiated cells near the opening of the crypt. It is concluded that cell swelling caused by short-chain fatty acids is a physiological stimulus for volume regulation. This response is restricted to the more differentiated cells.