Motoyori Kanazawa

Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome

Background  The profile of intestinal organic acids in irritable bowel syndrome (IBS) and its correlation with gastrointestinal (GI) symptoms are not clear. We hypothesized in this study that altered GI microbiota contribute to IBS symptoms through increased levels of organic acids.

Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity

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.

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.

Patients and nonconsulters with irritable bowel syndrome reporting a parental history of bowel problems have more impaired psychological distress

Little is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P < 0:001, for patients and 26.1 vs. 12.6%, P < 0:01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P < 0:001, for patients and 32.6 vs. 16.1%, P < 0:01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.

Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits.

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:One hundred twenty-nine 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 [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 with 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 with HC (909 ± 73 vs 563 ± 78, P < 0.01). Average barostat bag volume at baseline was higher (muscle tone lower) in HC compared with IBS-D and IBS-M but not compared with 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.

Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress.

Abstract  Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS), although the issue is still under debate. The aim of this study was to determine the prevalence of SIBO in those with IBS and its association with colonic motility, bowel symptoms and psychological distress. Sucrose hydrogen and methane breath tests were performed in 158 IBS patients 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 (IBS‐SS), IBS quality of life (IBS‐QOL) and self‐reported bowel symptoms. Fifty‐two of 158 (32.9%) IBS patients had abnormal breath tests compared with six of 34 (17.9%) HC (χ2 = 0.079). SIBO (SIBO+) and non‐SIBO (SIBO−) patients did not differ in the prevalence of IBS subtypes, IBS‐SS, IBS‐QOL and psychological distress variables. IBS patients had a greater post‐distension increase in MI than HC, but there was no difference between SIBO+ and SIBO− patients. 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 patients, and they reported more ‘hard or lumpy stools’ when compared with predominant hydrogen producers (P < 0.05) and SIBO− IBS patients (P < 0.05). SIBO is unlikely to contribute significantly to the pathogenesis of IBS. Methane production is associated with constipation.

Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention.

BACKGROUND AND AIMS Determining the gene that plays a key role in brain-gut interactions is a crucial step for clarifying the pathophysiology of irritable bowel syndrome (IBS). We previously reported that the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is related to anxiety in subjects with IBS. The amygdala is more activated during fearful face recognition in individuals with the s allele of 5-HTTLPR. Here, we tested our hypothesis that 5-HTTLPR differentially activates brain regions with colorectal distention in humans. METHODS We enrolled 28 subjects without any organic disease. The study was approved by the Ethics Committee and all subjects gave written informed consent. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Age, sex, diagnosis-matched individuals with the s/s genotype (n=14) and individuals with the l allele (genotypes l/s, l/l, l/extra-l, n=14) were compared. A barostat bag was inserted to the colorectum and was intermittently inflated with no (0 mm Hg), mild (20 mm Hg), or intense (40 mm Hg) stimulation on a random order. Radioactive H2[(15-)O] saline was injected at bag inflation and then positron emission tomography was performed. Changes in rCBF were analyzed using statistical parametric mapping. RESULTS Individuals with the s/s genotype showed a significantly larger increase in rCBF by colorectal distention from 0 mm Hg to 40 mm Hg than individuals with the l allele. The significantly more activated brain regions in individuals with the s/s genotype were the left anterior cingulate cortex and right parahippocampal gyrus (p<0.0001). The increase in rCBF by colorectal distention of 20 mm Hg compared with 0 mm Hg was significantly larger in the left orbitofrontal cortex of individuals with the s/s genotype than that of individuals with the l allele (p<0.0001). CONCLUSION These data suggest that individuals with a weak function of serotonin transporter respond to gut signals more in emotion-regulating brain regions. Functional gene polymorphism may partially predict the individual effect of a selective serotonin reuptake inhibitor on visceral pain.

Visceral hypersensitivity in irritable bowel syndrome

Altered central processing, abnormal gastrointestinal motility and visceral hypersensitivity may be possible major pathophysiology of irritable bowel syndrome (IBS). These factors affect each other and are probably associated with development of IBS symptoms.

Exaggerated motility of the descending colon with repetitive distention of the sigmoid colon in patients with irritable bowel syndrome

Background. Visceral hypersensitivity is one of the mechanisms of irritable bowel syndrome (IBS), but it does not explain the entire symptomatology, i.e., altered bowel habit with abdominal pain relieved by defecation. We tested our hypothesis that an abnormal link between luminal stimulation and mural response may have some role in the pathophysiology of IBS. Methods. Patients with IBS (n = 10, median 21 years old, 5 male patients, 5 female patients) and healthy control subjects (n = 10, median 21 years old, 5 men, 5 women) were studied. A manometric catheter with three transducers was inserted to the descending colon and a balloon was placed in the distal sigmoid colon. Another catheter with three transducers was inserted to the duodenum. After baseline for 30 min, the sigmoid colon was stimulated by balloon distention for 30 min followed by recovery for 30min. Balloon distention was repeated 100 times, and each stimulation consisted of a 5-s inflation and a 10-s deflation, with a volume of 50 ml maximum. The sensory threshold of balloon inflation was then examined, and plasma adrenocorticotropic hormone (ACTH) was measured with radioimmunoassay. Results. Repetitive colonie distention induced a significant increase in motility indices (mmHg s/s%) of the descending colon in the IBS patients (from 118 ± 25 to 333 ± 108, P < 0.05) but not of those in controls (from 90 ± 16 to 89 ± 19). A significant group difference (P < 0.05), period effect (P < 0.02), and group X period interactions (P < 0.01) were detected with two-way ANOVA. Duodenal motility indices in controls were significantly reduced by colonic distention (from 169 ± 25 to 104 ± 14, P < 0.01), but those in the IBS patients were not (from 156 ± 17 to 124 ± 20). The sensory threshold of balloon inflation in the IBS patients (74 ± 10 ml) was significantly lower than that in controls (125 ± 6 ml, P < 0.001). There was no significant difference in plasma ACTH levels between the IBS patients and controls. Conclusions. Repetitive distention of the distal sigmoid colon below the sensory threshold induced orad exaggerated motility of the colon in IBS patients. The distention inhibited motility of the small intestine in healthy subjects, but this inhibition was blunted in IBS patients. These results suggest that IBS patients may have not only visceral hypersensitivity, but also an abnormal intestinal reflex.

Gene, environment, and brain-gut interactions in irritable bowel syndrome.

The genetic predisposition and influence of environment may underlie in the pathogenesis and/or pathophysiology of irritable bowel syndrome (IBS). This phenomenon, gene x environment interaction together with brain‐gut interactions is emerging area to be clarified in IBS research. Earlier studies focused on candidate genes of neurotransmitters, cytokines, and growth factors. Among them, some studies but not all studies revealed association between phenotypes of IBS and 5‐hydroxytryptamine (5‐HT)‐related genes, noradrenaline‐related genes, and cytokine genes. Recent prospective cohort study showed that genes encoding immune and adhesion molecules were associated with post‐infectious etiology of IBS. Psychosocial stressors and intraluminal facotrs especially microrbiota are keys to develop IBS. IBS patients may have abnormal gut microbiota as well as increased organic acids. IBS is disorder that relates to brain‐gut interactions, emotional dysregulation, and illness behaviors. Brain imaging with or without combination of visceral stimulation enables us to depict the detailed information of brain‐gut interactions. In IBS patients, thalamus, insula, anterior cingulate cortex, amygdala, and brainstem were more activated in response to visceral stimulation than controls. Corticotropin‐releasing hormone and 5‐HT are the candidate substances which regulate exaggerated brain‐gut response. In conclusion, gene x environment interaction together with brain‐gut interactions may play crucial roles in IBS development. Further fundamental research on this issue is warranted.