Irritable Bowel Syndrome Subjects Research Articles

Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models.

We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (H2S)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii. In this study, we investigate the effects of increased methanogens or H2S producers on stool phenotypes in rat models. Adult Sprague-Dawley rats were fed high-fat diet (HFD) for 60days to increase M. smithii levels, then gavaged for 10days with water (controls) or methanogenesis inhibitors. To increase H2S producers, rats were gavaged with F. varium or D. piger. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples. In HFD diet-fed rats (N = 30), stool M. smithii levels wereincreased (P < 0.001) after 52days, correlating with significantly decreased SWW (P < 0.0001) at 59days (R = -0.38, P = 0.037). Small bowel M.smithii levels decreased significantly in lovastatin lactone-treated rats (P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (P = 0.0246), vs. controls (N = 10/group). SWW increased significantly in D.piger-gavaged rats (N = 16) on day 10 (P < 0.0001), and in F.varium-gavaged rats (N = 16) at all timepoints, vs. controls, with increased stool H2S production. 16S sequencing revealed stool microbiota alterations in rats gavaged with H2S producers, with higher relative abundance (RA) of other H2S producers, particularly Lachnospiraceae and Bilophila in F.varium-gavaged rats, and Sutterella in D.piger-gavaged rats. These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with H2S producers D.piger or F.varium results in increased colonization with other H2S producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and H2S producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.

Host epigenetics Gut microbiome interactions in irritable bowel syndrome subjects during Vitamin D supplementation

There is evidence of a link between vitamin D deficiency and Irritable Bowel Syndrome (IBS), and vitamin D supplementation can help improve it, but the mechanisms of this link still are unclear. In this study, we attempted to investigate the hostepigenetic -gut microbiome interactions during vitamin D supplementation in IBS patients

A multi-omic brain gut microbiome signature differs between IBS subjects with different bowel habits

Alterations of the brain-gut-microbiome system (BGM) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), yet bowel habit-specific alterations have not been elucidated. In this cross-sectional study, we apply a systems biology approach to characterize BGM patterns related to predominant bowel habit. Fecal samples and resting state fMRI were obtained from 102 premenopausal women (36 constipation-predominant IBS (IBS–C), 27 diarrhea-predominant IBS (IBS-D), 39 healthy controls (HCs)). Data integration analysis using latent components (DIABLO) was used to integrate data from the phenome, microbiome, metabolome, and resting-state connectome to predict HCs vs IBS-C vs IBS-D. Bloating and visceral sensitivity, distinguishing IBS from HC, were negatively associated with beneficial microbes and connectivity involving the orbitofrontal cortex. This suggests that gut interactions may generate aberrant central autonomic and descending pain pathways in IBS. The connection between IBS symptom duration, key microbes, and caudate connectivity may provide mechanistic insight to the chronicity of pain in IBS. Compared to IBS-C and HCs, IBS-D had higher levels of many key metabolites including tryptophan and phenylalanine, and increased connectivity between the sensorimotor and default mode networks; thus, suggestingan influence on diarrhea, self-related thoughts, and pain perception in IBS-D (‘bottom-up’ mechanism). IBS-C's microbiome and metabolome resembled HCs, but IBS-C had increased connectivity in the default mode and salience networks compared to IBS-D, which may indicate importance of visceral signals, suggesting a more ‘top-down’ BGM pathophysiology. These BGM characteristics highlight possible mechanistic differences for variations in the IBS bowel habit phenome.This article is part of the Special Issue on ‘Microbiome & the Brain: Mechanisms & Maladies’.

Cocultivation of Chinese prescription and intestine microbiota: SJZD alleviated the major symptoms of IBS-D subjects by tuning neurotransmitter metabolism.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a recurrent and common disease featuring dysbiotic intestinal microbiota, with limited treatments. Si-Jun-Zi Decoction (SJZD), a classic Chinese prescription, has been extensively used for IBS-D. This work aimed to explore the ex vivo interactions of SJZD and IBS-D's intestinal microbiota. Five samples of intestinal microbiota collected from IBS-D volunteers and five age-matched healthy controls were recruited from the Affiliated Hospital, Chengdu University of Traditional Chinese Medicine (TCM). A representative mixture of intestinal microbiota was composed of an equal proportion of these fecal samples. To simulate the clinical interaction, this microbiota was cocultivated with SJZD at clinical dosage in an anaerobic incubator at 37°C for 35 h. Microbiota and metabolic alterations were assessed by 16S rRNA gene sequencing in the V3/V4 regions and a nontargeted metabolome platform, respectively. After being cocultivated with SJZD, the dysbiotic intestine microbiota from IBS-D subjects was largely restored to those of the healthy controls. A total of 624 differentially expressed metabolites were detected by nontargeted metabolomics, of which 16 biomarkers were identified. These metabolites were then enriched into 11 pathways by KEGG, particularly those involved in neurotransmitter metabolism responses for the major symptom of IBS-D. Correlation analysis of bacterial metabolites demonstrated a synergistic pattern of neurotransmitter metabolism between Streptococcus and E. Shigella. SJZD rescued the dysbiotic intestinal microbiota and ameliorated the dysfunctional neurotransmitter metabolism involved in IBS-D's major symptoms.

Potential role of plasma miR-21 and miR-92a in distinguishing between irritable bowel syndrome, ulcerative colitis, and colorectal cancer.

This study aimed to investigate whether plasma miR-21 and miR-92a levels may be used to differentiate between patients with irritable bowel syndrome (IBS), ulcerative colitis (UC), and colorectal cancer (CRC). miRNA expression profiles are well characterized in CRC, but these expression profiles in UC and IBS remain promising. Screening of high-risk individuals for these diseases has substantial clinical benefits. This was a case-control study. We quantified plasma miR-21 and miR-92a expression levels in 100 samples (37 with active UC, 33 with CRC, and 30 with IBS as well as 30 healthy controls) using real-time PCR. Their diagnostic performance for discriminating these diseases was assessed using receiver-operation characteristic curve (AUC-ROC). The studied miRNAs were differentially expressed among all participated groups. Plasma miR-21 and miR-92a levels exhibited significant upregulation in CRC as compared to IBS, UC, and healthy subjects. Both miRNAs were upregulated in the UC group as compared to IBS and healthy subjects. ROC analysis revealed promising diagnostic performance for miR-21 and miR-92a in discriminating UC from non-UC groups (IBS and healthy subjects) with AUCs of 0.844 and 0.979 respectively. It also distinguished between CRC and UC with AUCs of 0.968 and 0.887 respectively and with reasonable sensitivities and specificities. Circulating miR-21 and miR-92a can be exploited not only as potential noninvasive biomarkers for detection of CRC, but also for differentiation between functional and organic colorectal disorders.

Downregulation of mucosal mast cell activation and immune response in diarrhoea-irritable bowel syndrome by oral disodium cromoglycate: A pilot study.

Diarrhoea-predominant irritable bowel syndrome (IBS-D) exhibits intestinal innate immune and mucosal mast cell (MC) activation. MC stabilisers have been shown to improve IBS symptoms but the mechanism is unclear. Our primary aim was to investigate the effect of oral disodium cromoglycate (DSCG) on jejunal MC activation and specific innate immune signalling pathways in IBS-D, and secondarily, its potential clinical benefit. Mucosal MC activation (by ultrastructural changes, tryptase release and gene expression) and innate immune signalling (by protein and gene expression) were quantified in jejunal biopsies from healthy (HS; n = 16) and IBS-D subjects after six months of either treatment with DSCG (600 mg/day, IBS-D-DSCG group; n = 18) or without treatment (IBS-D-NT group; n = 25). All IBS-D patients recorded abdominal pain and bowel habits at baseline and in the last 10 days prior to jejunal sampling. IBS-D-NT exhibited significant MC activation and over-expression of immune-related genes as compared to HS, whereas in IBS-D-DSCG MC activity and gene expression were similar to HS. Furthermore, DSCG significantly reduced abdominal pain and improved stool consistency. Oral DSCG modulates mucosal immune activity and improves gut symptoms in IBS-D patients. Future placebo-controlled clinical trials are needed for confirmation of clinical benefit of DSCG for IBS-D.

Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea‐predominant irritable bowel syndrome measured using serial MRI

BackgroundPrevious assessments of colon morphology have relied on tests which were either invasive or used ionizing radiation. We aimed to measure regional volumes of the undisturbed colon in healthy volunteers (HV) and patients with diarrhea-predominant irritable bowel syndrome (IBS-D).Methods3D regional (ascending, transverse, and descending) colon volumes were measured in fasting abdominal magnetic resonance (MR) images of 75 HVs and 25 IBS-D patients. Thirty-five of the HV and all 25 IBS-D subjects were fed a standard meal and postprandial MRI data obtained over 225 min.Key ResultsColonic regions were identified and 3D maps from cecum to sigmoid flexure were defined. Fasted regional volumes showed wide variation in both HVs being (mean ± SD) ascending colon (AC) 203 ± 75 mL, transverse (TC) 198 ± 79 mL, and descending (DC) 160 ± 86 mL with no difference from IBS-D subjects (AC 205 ± 69 mL, TC 232 ± 100 mL, and DC 151 ± 71 mL, respectively). The AC volume expanded by 10% after feeding (p = 0.007) in the 35 HV possibly due to increased ileo-colonic inflow. A later rise in AC volume occurred from t = 90 to t = 240 min as the meal residue entered the cecum. In contrast, IBS-D subjects showed a much reduced postprandial response of the AC (p < 0.0001) and a greater increase in TC volume after 90 min (p = 0.0244) compared to HV.Conclusions & InferencesWe have defined a normal range of the regional volumes of the undisturbed colon in fasted and fed states. The AC in IBS-D appeared less able to accommodate postprandial inflow which may account for faster colonic transit.

Su2084 Influence of Polymorphisms in the Cytokine Genes As Risk Factors for IBS and TMJD

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with still unknown pathophysiology presumed to develop due to complex interactions between the sensitizing effects of inflammation, CNS dis-inhibition, gut immunity, psychosocial stressors and genetic influences. Prior studies have shown an increase of proinflammatory cytokines IL-6, IL-1β, and TNF-α from mononuclear cells within the cecum of subjects with IBS. IBS is also frequently associated with other chronic pain conditions such as temporomandibular disorders (TMD), which has an inflammatory influence and is found in 16% of patients with IBS. Objective: The aim of our study was to evaluate whether specific cytokine genes previously found to be associated with TMD are also associated with IBS. We hypothesized that if these two pain disorders share common pathophysiologic mechanisms, then they may show similar associations with polymorphisms in the proinflammatory cytokine genes. Methods: A total of 122 women were enrolled in this study (72 with IBS, 25 with TMD, and 25 controls). IBS subjects were diagnosed using Rome II criteria and those with TMD were evaluated using the research diagnosis criteria for TMD (RDC). Single nucleotide polymorphisms (SNPs) to be genotyped were selected based on results of prior identified risk loci for pain sensitivity in subjects with TMD analyzed by our group. Peripheral blood samples from all participants were analyzed using restriction fragment length polymorphisms of PCR chain products. A Chi-Square statistical analysis was used to compare allele frequencies across IBS, TMD and controls and haplotypes were constructed using EM algorithm and the association between haplotypes and test groups. Results: IL1 β, IL6 and TNFα SNPs were significantly associated with IBS compared to controls and TMD (p value ,.05). Two IL1 β SNPs (rs700518, rs 1143634), one TNF α SNP (rs1800629) and IL6 SNP were associated with IBS (p value , .05) versus controls. For IBS versus TMD, significant differences in allele frequencies emerged in the following SNPs, IL1 β (rs16944) and TNFα -(rs1800629 and rs1800683). The two-SNP haplotype of the TNF α gene was strongly associated with IBS compared with TMD and controls (p,0.0001). None of these polymorphisms were associated with TMD. Conclusion: Polymorphisms in specific cytokine genes may be a risk factor for IBS. The presence of the haplotype formed by SNPs rs1800629 and rs1800683 in the TNFα gene may increase the susceptibility to IBS in women. The lack of significance associations with TMD however may be due to our small sample size.

A Pilot Study of Gene Expression Profiling to Differentiate Irritable Bowel Syndrome Subjects From Normal Controls

A Pilot Study of Gene Expression Profiling to Differentiate Irritable Bowel Syndrome Subjects From Normal Controls

Real-time PCR analysis of enteric pathogens from fecal samples of irritable bowel syndrome subjects.

BackgroundGrowing amount of scientific evidence suggests that microbes are involved in the pathophysiology of irritable bowel syndrome (IBS). The predominant fecal microbiota composition of IBS subjects has been widely studied with DNA-based techniques but less research has been focused on the intestinal pathogens in this disorder. Here, we optimized a highly sensitive panel of 12 quantitative real-time PCR (qPCR) assays to shed light on the putative presence of intestinal pathogens in IBS sufferers. The panel was used to screen fecal samples from 96 IBS subjects and 23 healthy controls.ResultsFifteen IBS samples (17%) tested positive for Staphylococcus aureus with a thermonuclease (nuc) gene-targeting qPCR assay, whereas none of the healthy controls were positive for S. aureus (p <0.05). The S. aureus -positive IBS samples were confirmed by sequencing of the PCR amplicons. Clostridium perfringens was detected from IBS and control groups with a similar frequency (13% and 17%, respectively) with α-toxin (plc) gene -targeting qPCR assay while none of the samples tested positive for the Cl. perfringens enterotoxin-encoding gene (cpe).ConclusionsThe qPCR panel consisting of 12 assays for an extensive set of pathogenic microorganisms provides an efficient alternative to the conventional detection of gastrointestinal pathogens and could accelerate the initiation of targeted antibiotic therapy reducing the risk of post-infectious IBS (PI-IBS). S. aureus has not been previously reported to be associated with the onset of IBS. Although we discovered significant differences in the prevalence of S. aureus between the study groups, its importance in giving rise to IBS symptoms requires further studies.

Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon‐gamma, severity of symptoms and psychiatric co‐morbidity

Irritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.

Gallstones, cholecystectomy and irritable bowel syndrome (IBS)

Subjects with irritable bowel syndrome may undergo an excess of cholecystectomy. It is not known, however, whether the cholecystectomy rate parallels an increased risk of gallstones. Aim was to assess the prevalence and the incidence of gallstones and cholecystectomy in subjects with irritable bowel syndrome symptoms. In this population-based study, 29,139 subjects (63.2% of 46,139 randomly selected subjects, age 30-69 years) underwent a physical examination, an interview on gastrointestinal symptoms and an upper abdominal ultrasonography. An identical survey was carried out 7.8+/-1.0 (M+/-S.D.) years later on 8460 gallstone-free subjects at the first survey. Prevalence and incidence of gallstones and cholecystectomy were assessed in subjects with (1) irritable bowel syndrome; (2) abdominal pain and normal bowel; (3) altered bowel and no abdominal pain and (4) asymptomatic controls; univariate and multivariate regression logistic models were used for statistical analysis. Prevalence odds of gallstones and cholecystectomy were significantly higher in irritable bowel syndrome and abdominal pain and normal bowel than in controls. Irritable bowel syndrome and abdominal pain and normal bowel subjects were more aware of gallstones than controls (p<0.001), and the prevalence of gallstones in irritable bowel syndrome subjects unaware of their gallbladder status was not significantly different from the controls. The incidence of gallstone disease in irritable bowel syndrome, abdominal pain and normal bowel, and altered bowel and no abdominal pain subjects did not differ from the controls. The incidence of cholecystectomy was higher in irritable bowel syndrome and abdominal pain and normal bowel groups than in controls and altered bowel and no abdominal pain group. Irritable bowel syndrome subjects have an increased risk of cholecystectomy that is not due to an increased risk of gallstones, but rather to abdominal pain, awareness of having gallstones, and inappropriate surgical indications.

Prevalence of irritable bowel syndrome in Korea: Population‐based survey using the Rome II criteria

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder in the West. But information on the prevalence of IBS in Asia is still lacking, especially in Korea. Therefore, the aims of the present study were to estimate the prevalence of IBS in the general population of Korea and also to investigate characteristics of IBS and health-care-seeking behavior of IBS patients. Telephone interview survey was conducted by Gallup, Korea using a validated questionnaire based on the Rome II criteria. The response rate of the telephone interview survey was 25.2% (n = 1066, 535 male and 531 female responders). A random sample of gender and age (between 18 and 60 years), based on a per capita ratio was obtained. Among 1066 subjects, the prevalence of IBS was 6.6% (70 subjects; 7.1%, male; 6.0%, female). The difference in IBS prevalence by gender was not significant. The prevalence was higher among those in their 20s (P = 0.036). Among 70 subjects with IBS, 10/20 IBS subjects sought health care due to abdominal pain. Among the risk factors of IBS, marital status had a significant difference; the following risk factors are arranged in descending order: age (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 0.85-2.25), alcohol intake (OR: 1.38, 95%CI: 0.81-2.35), gender (OR: 1.19, 95%CI: 0.73-1.94), demographics (OR: 1.09, 95%CI: 0.53-2.25), income (OR: 0.88, 95%CI: 0.54-1.45), education level (OR: 0.81, 95%CI: 0.46-1.40), smoking (OR: 0.64, 95%CI: 0.37-1.12), and marital status (OR: 0.59, 95%CI: 0.35-0.99). The prevalence of IBS in the Korean population is 6.6%, and the male:female ratio is similar. Also, IBS is more frequent in younger subjects. Irritable bowel syndrome subjects visited a physician mostly due to abdominal pain.

Stability of irritable bowel syndrome using a Rome II‐based classification

As there is no biological marker for irritable bowel syndrome, a diagnosis is made using symptom-based criteria. To evaluate the stability of self-reported symptoms consistent with Rome II-based irritable bowel syndrome classification. Irritable bowel syndrome subjects identified in a 2001 population-based study by modified Rome II criteria were re-contacted 2 years later. Data were collected via a web-based questionnaire. Of the 697 subjects, 30% remained in the same irritable bowel syndrome subtype in both surveys, 18.4% changed irritable bowel syndrome subtype and 52% no longer met the irritable bowel syndrome criteria at follow-up. Subjects continuing to meet the irritable bowel syndrome criteria were more likely to have been initially classified in the alternating irritable bowel syndrome subtype and had more psychological impairment and lower irritable bowel syndrome-related quality of life than subjects not fulfilling the irritable bowel syndrome criteria at follow-up. Lack of pain caused more subjects to fall out of the irritable bowel syndrome criteria than the absence of non-painful bowel symptoms. However, the majority of subjects that did not fulfill the pain component of the irritable bowel syndrome criteria continued to report abdominal pain of at least moderate severity. In a US population-based follow-up study using modified Rome II criteria, we found irritable bowel syndrome is episodic in nature and current classification is limited in capturing fluctuation of disease over time.

Gender difference on the symptoms, health‐seeking behaviour, social impact and sleep quality in irritable bowel syndrome: a Rome II‐based survey in an apparent healthy adult Chinese population in Taiwan

Little is known about the gender effect on irritable bowel syndrome in Asia. To assess the gender difference in Chinese subjects with irritable bowel syndrome meeting Rome II criteria. Irritable bowel syndrome was identified from an apparently healthy adult population receiving a routine health maintenance program (n = 2018). Female gender is not a factor associated with irritable bowel syndrome or irritable bowel syndrome-related health care-seeking behaviour. Female irritable bowel syndrome subjects, irrespective of consulting behaviour for irritable bowel syndrome, are likely to have < 3 bowel movements/week, hard/lumpy stools and abdominal fullness/bloating (P < 0.05). Female irritable bowel syndrome subjects are prone to be absent from school/work with more days of absenteeism, irrespective of consultation status (P < 0.05). Only female irritable bowel syndrome consulters have more absenteeism for their irritable bowel syndrome-related symptoms, reporting more sleep disturbances than their male counterparts (P < 0.001). In an apparent healthy adult population in Taiwan, gender difference is present in Rome II defined Chinese subjects with irritable bowel syndrome as regards bowel symptoms, social impact and sleep quality. Female predominance was not found in irritable bowel syndrome subjects and irritable bowel syndrome-related health care-seeking behaviour in the current population. Both irritable bowel syndrome non-consulters and consulters have similar gender difference profiles in presenting symptoms, suggesting that bowel symptoms per se may not be the only factor leading to health care-seeking behaviour. The gender differences in sleep problems were observed solely in irritable bowel syndrome consulter.

Current patterns of irritable bowel syndrome in Taiwan: the Rome II questionnaire on a Chinese population.

Irritable bowel syndrome is a common condition seen in Western countries. In Asia, however, it is less known and even less studied. To determine the prevalence and social impact of irritable bowel syndrome as well as the health-seeking behaviour of irritable bowel syndrome patients in Taiwan Using the modified Rome II questionnaire, a survey was carried out in a population receiving physical check-up (n = 2865). The prevalence of irritable bowel syndrome in Taiwan was 22.1% and 17.5% (kappa = 0.73) according to the Rome II and I criteria, respectively. No gender difference was found between subjects with and without irritable bowel syndrome symptoms. Irritable bowel syndrome subjects were likely to undertake an excessive number of physician-visits (P < 0.01). Such subjects were often absent from work/school, with more days of absenteeism than irritable bowel syndrome-free subjects (P < 0.01). They also suffered obvious sleep disturbance (P < 0.01). Nearly half of the irritable bowel syndrome subjects were 'consulters', and they were more likely to have frequent physician-visits, suffer from work/school absenteeism, and endure sleep disturbance and bowel symptoms than irritable bowel syndrome nonconsulters (P < 0.05). Irritable bowel syndrome is common in a Chinese population of Taiwan. Similar to irritable bowel syndrome in the West, it also involves significant social and medical burdens. However, in the irritable bowel syndrome subjects of Taiwan there is no gender difference, and more irritable bowel syndrome subjects will seek physician consultations, which may be due to Taiwan's easily accessible and affordable heath care facilities.

Stimulation of the nitric oxide–guanosine 3′, 5′-cyclic monophosphate pathway by sildenafil: Effect on rectal muscle tone, distensibility, and perception in health and in irritable bowel syndrome

Objectives Nitric oxide, a neurotransmitter in the noncholinergic, nonadrenergic nervous system, is a mediator of relaxation of GI smooth muscle and of visceral nociception mainly studied in vitro. Sildenafil stimulates the nitric oxide guanosine 3′, 5′-cyclic monophosphate (NO-cGMP) pathway through inhibition of phosphodiesterase 5. The aims of this study were to evaluate in vivo the effect of stimulation of the NO-cGMP pathway on rectal tone, distensibility, and perception in healthy individuals and in patients with irritable bowel syndrome (IBS). Methods In eight healthy subjects and four patients with IBS rectal tone, distensibility and perception thresholds were measured with an electronic barostat both before and 60 min after administration of sildenafil (50 mg p.o.). Perception was scored on a graded scale of 0–6. At the end of a distension series an anatomic questionnaire was filled out by the subjects. Results Sildenafil significantly reduced rectal tone in healthy subjects (intrabag volume predrug: 145.5 ± 18.7 ml vs postdrug: 164.4 ± 16.9 ml, p = 0.01) and IBS (111.3 ± 25.2 ml vs 136.5 ± 33.3 ml; p = 0.01) but did not alter rectal compliance (healthy subjects: 5.8 ± 0.4 vs 6.3 ± 0.6 ml/mm Hg, p > 0.05; IBS subjects: 6.1 ± 0.6 vs 7.1 ± 1.0 ml/mm Hg, p > 0.05). Intrabag pressure and rectal wall tension to reach perception thresholds for initial sensation, sensation of stool, and urgency were not altered by sildenafil. However, intrabag volumes to reach these thresholds were significantly increased by sildenafil both in healthy subjects and in patients with IBS. Viscerosomatic referral was unchanged. Conclusions Stimulation of the NO-cGMP pathway decreases rectal tone but does not influence rectal distensibility. Relaxation of the rectum is accompanied by an increase in rectal volumes to reach perception thresholds in healthy subjects and in patients with IBS, but no direct effect on rectal perception can be demonstrated.

Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test, suggesting bacterial overgrowth.

We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case-control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 +/- 0.8 in IBS subjects and 2.2 +/- 1.0 in controls (P < 0.000001). The duration of phase III was 305 +/- 123 sec in IBS subjects and 428 +/- 173 in controls (P < 0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P < 0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.

Response to intraluminal gas in irritable bowel syndrome

Our aim was to evaluate the response to intraluminal gas in irritable bowel syndrome and to determine whether this response was consequent upon disordered motility or altered perception. We evaluated 10 patients who satisfied the clinical criteria for the diagnosis of irritable bowel syndrome and 10 healthy controls. An eight-lumen perfused catheter assembly was positioned to monitor motor activity in the duodenum and proximal jejunum; a separate side port in the distal duodenum permitted gas infusion. Subjects recorded symptoms of abdominal pain, bloating, and nausea throughout the study, using a visual analog scale. Following an overnight fast and a 60-min basal recording period in the fasted state, subjects ate a standard meal; 60 min later, "sham" gas was administered for 20 min, followed by the actual infusion of nitrogen gas at 40 ml/min. Subjects were randomized to receive atropine (7 micrograms/kg) or placebo intravenously during the period of actual gas infusion. Patients with irritable bowel syndrome described more pain (score, mean +/- SE, control versus irritable bowel: 0.22 +/- 0.16 vs 1.65 +/- 0.5, P < 0.01) and nausea (0.25 +/- 0.21 vs 1.45 +/- 0.64, P < 0.04) during sham gas; motility indices were similar in both groups. During active gas, irritable bowel syndrome patients reported more pain (0.40 +/- 0.39 vs 2.94 +/- 1.16, P < 0.03); motility indices at all sites were similar in both groups. Symptom severity in irritable bowel syndrome subjects randomized to receive atropine was similar to control subjects during active gas infusion; motility indices were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Faecal weight, constituents, colonic motility, and lactose tolerance in the irritable bowel syndrome.

Lactose intolerance and faecal characteristics were compared in 16 patients with symptomatic irritable bowel syndrome and in age- and sex-matched controls. Faecal stool weight was increased in the irritable bowel syndrome patients, whereas faecal bile acids, fat, volatile fatty acids, and neutral sterols were not significantly different. No lactose intolerance was found in irritable bowel syndrome subjects. Measurements of colonic motility showed only modest activity for both basal and food-stimulated activity. There was a weak correlation between the concentration of total bile acids, deoxycholic acid, lithocholic acid and the motility index.