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1.  Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: Association with Colon Motility, Bowel Symptoms, and Psychological Distress 
Background
Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS), although with significant controversy.
Aims
To determine the prevalence of SIBO in IBS and its association with colonic motility, bowel symptoms and psychological distress.
Methods
Sucrose hydrogen and methane breath tests were performed in 158 IBS and 34 healthy controls (HC). Thresholds for pain and urgency were tested by barostat in the descending colon. The motility index (MI) was calculated as the average area under the curve for all phasic contractions. Questionnaires assessed psychological distress, IBS symptom severity (IBSSS), IBS Quality of Life (IBS-QOL) and self reported bowel symptoms.
Results
52/158 (32.9%) IBS patients had abnormal breath tests compared with 6/34 (17.9%) HC (χ2=0.079). SIBO (SIBO+) and Non-SIBO (SIBO−) did not differ in the prevalence of IBS-subtypes, IBS-SS, IBS-QOL and psychological distress variables. IBS had a greater post-distension increase in MI than HC, but there was no difference between SIBO+ and SIBO−. Predominant methane producers had higher urge thresholds (28.4 vs. 18.3, p<0.05) and higher baseline MI (461 vs. 301.45, p<0.05) than SIBO− IBS, and they reported more “hard or lumpy stools” when compared to predominant hydrogen producers (p<0.05) and SIBO− IBS (p< 0.05).
Conclusions
SIBO is unlikely to contribute significantly in the pathogenesis of IBS. Methane production is associated with constipation.
doi:10.1111/j.1365-2982.2008.01142.x
PMCID: PMC3856223  PMID: 18482250
Small intestinal bacterial overgrowth; Irritable bowel syndrome; Breath test; Methane; Constipation; Visceral hypersensitivity; Psychological
2.  Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits 
The American journal of gastroenterology  2008;103(10):10.1111/j.1572-0241.2008.02066.x.
Objectives
Irritable bowel syndrome (IBS) patients show pain hypersensitivity and hypercontractility in response to colonic or rectal distention. Aims were to determine whether predominant bowel habits and IBS symptom severity are related to pain sensitivity, colon motility, or smooth muscle tone.
Methods
129 patients classified as IBS with diarrhea (IBS-D, n=44), IBS with constipation (IBS-C, n=29), mixed IBS (IBS-M, n=45) and unspecified IBS (IBS-U, n=11) based on stool consistency, and 30 healthy controls (HC) were studied. A manometric catheter containing a 600-ml capacity plastic bag was positioned in the descending colon. Pain threshold was assessed using a barostat. Motility was assessed for 10 min with the bag minimally inflated (individual operating pressure or IOP), 10 min at 20 mmHg above the IOP, and for 15-min recovery following bag inflation. Motility was also recorded for 30 min following an 810-kcal meal.
Results
Compared to HC, IBS patients had lower pain thresholds (medians: 30 vs. 40 mmHg, p<0.01), but IBS subtypes were not different. IBS symptom severity was correlated with pain thresholds (rho=-0.36, p<0.001). During distention, the motility index (MI) was significantly higher in IBS compared to HC (909±73 vs. 563±78, p<0.01). Average barostat bag volume at baseline was higher (muscle tone lower) in HC compared to IBS-D and IBS-M but not compared to IBS-C. The baseline MI and bag volume differed between IBS-D and IBS-C and correlated with symptoms of abdominal distention and dissatisfaction with bowel movements. Pain thresholds and MI during distention were uncorrelated.
Conclusions
Pain sensitivity and colon motility are independent factors contributing to IBS symptoms. Treatment may need to address both and to be specific to predominant bowel habit.
doi:10.1111/j.1572-0241.2008.02066.x
PMCID: PMC3855425  PMID: 18684175
irritable bowel syndrome; visceral hypersensitivity; colonic motility; symptom severity; subtypes of bowel habit
3.  Corticotropin-Releasing Hormone Receptor 1 Gene Variants in Irritable Bowel Syndrome 
PLoS ONE  2012;7(9):e42450.
Background
Corticotropin-releasing hormone (CRH) acts mainly via the CRH receptor 1 (CRH-R1) and plays a crucial role in the stress-induced pathophysiology of irritable bowel syndrome (IBS). Several studies have demonstrated that variants of the CRH-R1 gene carry a potential risk for depression, but evidence for an association between CRH-R1 genotypes and IBS is lacking. We tested the hypothesis that genetic polymorphisms and haplotypes of CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients.
Methods
A total of 103 patients with IBS and 142 healthy controls participated in the study. Three single-nucleotide polymorphisms of the CRH-R1 gene (rs7209436, rs242924, and rs110402) were genotyped. Subjects' emotional states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-rating Depression Scale.
Results
The TT genotype of rs7209436 (P = 0.01) and rs242924 (P = 0.02) was significantly more common in patients with IBS than in controls. Total sample analysis showed significant association between bowel pattern (normal, diarrhea, constipation, or mixed symptoms) and the T allele of rs7209436 (P = 0.008), T allele of rs242924 (P = 0.019), A allele of rs110402 (P = 0.047), and TAT haplocopies (P = 0.048). Negative emotion was not associated with the examined CRH-R1 SNPs.
Conclusion
These findings suggest that genetic polymorphisms and the CRH-R1 haplotypes moderate IBS and related bowel patterns. There was no clear association between CRH-R1 genotypes and negative emotion accompanying IBS. Further studies on the CRH system are therefore warranted.
doi:10.1371/journal.pone.0042450
PMCID: PMC3434156  PMID: 22957021
4.  Enhanced Auditory Brainstem Response and Parental Bonding Style in Children with Gastrointestinal Symptoms 
PLoS ONE  2012;7(3):e32913.
Background
The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS) are unclear. We hypothesized that children with chronic gastrointestinal (GI) symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP) responses and receive more inadequate parental bonding.
Methodology/Principal Findings
Children aged seven and their mothers (141 pairs) participated. BAEP was measured by summation of 1,000 waves of the electroencephalogram triggered by 75 dB click sounds. The mothers completed their Children's Somatization Inventory (CSI) and Parental Bonding Instrument (PBI). CSI results revealed 66 (42%) children without GI symptoms (controls) and 75 (58%) children with one or more GI symptoms (GI group). The III wave in the GI group (median 4.10 interquartile range [3.95–4.24] ms right, 4.04 [3.90–4.18] ms left) had a significantly shorter peak latency than controls (4.18 [4.06–4.34] ms right, p = 0.032, 4.13 [4.02–4.24] ms left, p = 0.018). The female GI group showed a significantly shorter peak latency of the III wave (4.00 [3.90–4.18] ms) than controls (4.18 [3.97–4.31] ms, p = 0.034) in the right side. BAEP in the male GI group did not significantly differ from that in controls. GI scores showed a significant correlation with the peak latency of the III wave in the left side (rho = −0.192, p = 0.025). The maternal care PBI scores in the GI group (29 [26]–[33]) were significantly lower than controls (31 [28.5–33], p = 0.010), while the maternal over-protection PBI scores were significantly higher in the GI group (16 [12]–[17]) than controls (13 [10.5–16], p = 0.024). Multiple regression analysis in females also supported these findings.
Conclusions
It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms.
doi:10.1371/journal.pone.0032913
PMCID: PMC3310045  PMID: 22470430
5.  Biopsychosocial Model of Irritable Bowel Syndrome 
Irritable bowel syndrome (IBS) is a common chronic disorder seen in gastroenterology and primary care practice. It is characterized by recurrent abdominal pain or discomfort associated with disturbed bowel function. It is a heterogeneous disorder with varying treatments, and in this regard physicians sometimes struggle with finding the optimal approach to management of patients with IBS. This disorder induces high health care costs and variably reduces health-related quality of life. IBS is in the class of functional gastrointestinal disorders, and results from dysregulation of central and enteric nervous system interactions. Psychosocial factors are closely related to their gut physiology, associated cognitions, symptom manifestations and illness behavior. Therefore, it is important for the physician to recognize the psychosocial issues of patients with IBS and in addition to build a good patient-physician relationship in order to optimize treatment. This review focuses on the interaction between psychological and physiological factors associated with IBS by using a biopsychosocial model. In this article, we describe (1) the predisposing psychological features seen in early life; (2) the psychological factors associated with life stress, the symptom presentation, and their associated coping patterns; (3) gut pathophysiology with emphasis on disturbances in motility, visceral hypersensitivity and brain-gut interactions; and finally (4) the clinical outcomes and effective treatments including psychotherapeutic methods.
doi:10.5056/jnm.2011.17.2.131
PMCID: PMC3093004  PMID: 21602989
Irritable bowel syndrome; Pathophysiology; Psychology
6.  Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity 
Gut  2007;56(9):1202-1209.
Objective
The aim was to determine whether lower visceral pain thresholds in irritable bowel syndrome (IBS) primarily reflect physiological or psychological factors.
Methods
Firstly, 121 IBS patients and 28 controls underwent balloon distensions in the descending colon using the ascending methods of limits (AML) to assess pain and urge thresholds. Secondly, sensory decision theory analysis was used to separate physiological from psychological components of perception: neurosensory sensitivity (p(A)) was measured by the ability to discriminate between 30 mm Hg vs 34 mm Hg distensions; psychological influences were measured by the report criterion—that is, the overall tendency to report pain, indexed by the median intensity rating for all distensions, independent of intensity. Psychological symptoms were assessed using the Brief Symptom Inventory (BSI).
Results
IBS patients had lower AML pain thresholds (median: 28 mm Hg vs 40 mm Hg; p<0.001), but similar neurosensory sensitivity (median p(A): 0.5 vs 0.5; p = 0.69; 42.6% vs 42.9% were able to discriminate between the stimuli better than chance) and a greater tendency to report pain (median report criterion: 4.0 (“mild” pain) vs 5.2 (“weak” pain); p = 0.003). AML pain thresholds were not correlated with neurosensory sensitivity (r = −0.13; p = 0.14), but were strongly correlated with report criterion (r = 0.67; p<0.0001). Report criterion was inversely correlated with BSI somatisation (r = −0.26; p = 0.001) and BSI global score (r = −0.18; p = 0.035). Similar results were seen for the non‐painful sensation of urgency.
Conclusion
Increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity.
doi:10.1136/gut.2006.117390
PMCID: PMC1954968  PMID: 17483191
hypersensitivity; hypervigilance; perceptual response bias; irritable bowel syndrome
7.  Changes in salivary physiological stress markers induced by muscle stretching in patients with irritable bowel syndrome 
Background
Psychophysiological processing has been reported to play a crucial role in irritable bowel syndrome (IBS) but there has been no report on modulation of the stress marker chromogranin A (CgA) resulting from muscle stretching. We hypothesized that abdominal muscle stretching as a passive operation would have a beneficial effect on a biochemical index of the activity of the sympathetic/adrenomedullary system (salivary CgA) and anxiety.
Methods
Fifteen control and eighteen untreated IBS subjects underwent experimental abdominal muscle stretching for 4 min. Subjects relaxed in a supine position with their knees fully flexed while their pelvic and trunk rotation was passively and slowly moved from 0 degrees of abdominal rotation to about 90 degrees or the point where the subject reported feeling discomfort.
Changes in the Gastrointestinal Symptoms Rating Scale (GSRS), State Trait Anxiety Inventory (STAI), Self-rating Depression Scale (SDS), ordinate scale and salivary CgA levels were compared between controls and IBS subjects before and after stretching. A three-factor analysis of variance (ANOVA) with period (before vs. after) as the within-subject factor and group (IBS vs. Control), and sex (men vs. female) as the between-subject factors was carried out on salivary CgA.
Results
CgA showed significant interactions between period and groups (F[1, 31] = 4.89, p = 0.03), and between groups and sex (F[1, 31] = 4.73, p = 0.03). Interactions between period and sex of CgA secretion were not shown (F[1, 3] = 2.60, p = 0.12). At the baseline, salivary CgA in IBS subjects (36.7 ± 5.9 pmol/mg) was significantly higher than in controls (19.9 ± 5.5 pmol/mg, p < 0.05). After the stretching, salivary CgA significantly decreased in the IBS group (25.5 ± 4.5 pmol/mg), and this value did not differ from that in controls (18.6 ± 3.9 pmol/mg).
Conclusion
Our results suggest the possibility of improving IBS pathophysiology by passive abdominal muscle stretching as indicated by CgA, a biochemical index of the activity of the sympathetic/adrenomedullary system.
doi:10.1186/1751-0759-2-20
PMCID: PMC2588633  PMID: 18983682
8.  Translation and validation of a Japanese version of the irritable bowel syndrome-quality of life measure (IBS-QOL-J) 
Aims
To compare quality of life (QOL) for patients with irritable bowel syndrome (IBS) between the U.S. and Japan, it is indispensable to develop common instruments. The IBS-QOL, which is widely used in Western countries, was translated into Japanese as there has been a lack of Japanese disease-specific QOL measures for IBS.
Methods
The original 34 items of the IBS-QOL were translated from English into Japanese through two independent forward translations, resolution, back translation, and resolution of differences. Forty nine patients who had GI symptoms but did not have any organic diseases (including 30 IBS patients diagnosed by Rome II criteria) were recruited from Tohoku University Hospital in Sendai, Japan and completed a Japanese version of the IBS-QOL (IBS-QOL-J) concomitant with a Japanese version of the IBS severity index (IBSSI-J) twice within 7–14 days.
Results
The IBS-QOL-J demonstrated high internal consistency (Cronbach's alpha; 0.96) and high reproducibility (intraclass correlation coefficient; 0.92, p < 0.001). Convergent analyses confirmed that the overall score of IBS-QOL-J was significantly correlated with overall severity of IBS symptoms on the IBSSI-J (r = -0.36, p = 0.01) and with the individual items on the IBSSI-J that assess interference with life in general (r = -0.47, p = 0.001) and dissatisfaction with bowel habits (r = -0.32, p < 0.05). Eight patients who reported continuous abdominal pain in the past 6 months had significantly lower scores in the IBS-QOL-J than those who did not (53.7 +- 12.7 vs. 73.6 +- 19.5, p < 0.01). Age, sex, education or marital status did not affect scores on the measure.
Conclusion
The IBS-QOL-J is a reliable instrument to assess the disease-specific QOL for IBS. Considering cross-cultural comparison, this measure is likely to be a valuable tool to investigate the QOL in Japanese patients with IBS.
doi:10.1186/1751-0759-1-6
PMCID: PMC1832201  PMID: 17371576

Results 1-8 (8)