Stool and urine trefoil factor 3 levels: associations with symptoms, intestinal permeability, and microbial diversity in irritable bowel syndrome.

Previously we showed that urine trefoil factor 3 (TFF3) levels were higher in females with irritable bowel syndrome (IBS) compared to non-IBS females. To assess if TFF3 is associated with symptoms and/or reflect alterations in gastrointestinal permeability and gut microbiota in an IBS population, we correlated stool and urine TFF3 levels with IBS symptoms, intestinal permeability, stool microbial diversity and relative abundance of predominant bacterial families and genera. We also tested the relationship of stool TFF3 to urine TFF3, and compared results based on hormone contraception use. Samples were obtained from 93 females meeting Rome III IBS criteria and completing 4-week symptom diaries. TFF3 levels were measured by ELISA. Permeability was assessed with the urine lactulose/mannitol (L/M) ratio. Stool microbiota was assessed using 16S rRNA. Stool TFF3, but not urine TFF3, was associated positively with diarrhoea and loose stool consistency. Higher stool TFF3 was also associated with lower L/M ratio and microbial diversity. Of the 20 most abundant bacterial families Mogibacteriaceae and Christensenellaceae were inversely related to stool TFF3, with only Christensenellaceae remaining significant after multiple comparison adjustment. There were no significant relationships between stool or urine TFF3 levels and other symptoms, nor between stool and urine levels. In premenopausal females, urine TFF3 levels were higher in those reporting hormone contraception. Collectively these results suggest that higher stool TFF3 levels are associated with IBS symptoms (loose/diarrhoeal stools), lower gut permeability, and altered stool bacteria composition (decreased diversity and decreased Christensenellaceae), which further suggests that TFF3 may be an important marker of host-bacteria interaction.

Sleep disturbances in irritable bowel syndrome: a systematic review.

BACKGROUND: Sleep disturbances are well-documented among persons with irritable bowel syndrome (IBS). Difficulty in falling asleep, shorter sleep time, frequent arousal and awakenings, or non-restorative sleep are the most common manifestations. Sleep disturbances are also related to a higher risk of having IBS. Some researchers have provided evidence of a positive association between poorer subjective sleep quality and increased severity and frequency in gastrointestinal (GI) symptoms in those with IBS. However, findings from studies using objective sleep and activity measures, such as polysomnography and actigraphy, are inconclusive. PURPOSE: This systematic review of the literature between 1990 and 2015 evaluates the evidence of sleep disturbances in adults with IBS and their relationship with GI symptoms.

Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. METHODS: Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test. KEY RESULTS: As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS-diarrhea [IBS-D], IBS-constipation plus mixed [IBS-CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS-CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS-CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. CONCLUSIONS & INFERENCES: Despite similar levels of abdominal pain in IBS, the IBS-CM group demonstrated greater sensitivity to both thermal and visceral testing procedures.

Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal axis in women with irritable bowel syndrome.

BACKGROUND: Evidence suggests that subgroups of patients with irritable bowel syndrome (IBS) are hyper-responsive to a variety of laboratory stress conditions. METHODS: This study compared sleep quality and night time plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to anticipation of public speaking between 43 women with IBS and 24 healthy control women. In addition, comparisons were made between subgroups within the IBS sample based on predominant stool patterns, 22 IBS-constipation and 21 IBS-diarrhea. Subjects slept three nights in a sleep laboratory, and on the third night serial blood samples were drawn every 20 min from 08:00 PM until awakening. As the subjects had different sleep onsets, each subject's results were synchronized to the first onset of stage 2 sleep. KEY RESULTS: Compared the healthy control group, women with IBS had significantly worse sleep efficiency, and higher cortisol but not ACTH levels over the night. However, there were no IBS bowel pattern subgroup differences. Among IBS subjects, cortisol levels early in the night were higher than found in our previous study with a similar protocol but without the threat of public speaking. These results suggest that a social stressor, such as public speaking prior to bedtime, increases cortisol but not ACTH levels suggesting HPA dysregulation in women with IBS. CONCLUSIONS & INFERENCES: This response to a social stressor contributes to our understanding of the relationship of stress to symptom expression in IBS.

Associations of tryptophan hydroxylase gene polymorphisms with irritable bowel syndrome.

BACKGROUND: Alterations in serotonin (5-HT) are suspected in the pathophysiology of irritable bowel syndrome (IBS). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin and has two isoforms: TPH1 and TPH2. Genetic variants in both genes have been studied in various disorders related to serotonin dysregulation. The aim of this study was to examine whether TPH gene variants were associated with IBS and IBS-related gastrointestinal (GI) symptoms. METHODS: Five single nucleotide polymorphisms (SNPs) from the TPH1 and one SNP from the TPH2 were genotyped in 199 IBS patients and 79 healthy controls. All subjects were Caucasian women of European origin. Irritable bowel syndrome patients filled in a daily diary with five GI symptoms and stool characteristics for 28 days. KEY RESULTS: The TPH1 SNPs showed no association with the diagnosis of IBS. However, among IBS patients, all five TPH1 SNPs showed some association with diarrhea and loose type of stool consistency, with P-values rating from 0.01 to 0.20. The TPH2 SNP showed a trend towards a reduced risk of IBS and possible associations with stool characteristics, both hard and loose stools. However, no P-values were less than the conservative multiple-comparison-adjusted threshold of 0.001 and hence these results must be interpreted cautiously. CONCLUSIONS & INFERENCES: This study is the first to assess associations of TPH gene variants with IBS-related GI symptoms and stool characteristics. The possible association of TPH gene variants with diarrhea needs to be verified in an independent sample.

Enterocoele is a marker of severe pelvic floor weakness.

OBJECTIVE: The aim was to evaluate the relationship between the presence of an enterocoele and grade of rectal prolapse (RP). METHOD: Defaecating proctograms of consecutive patients presenting to the Oxford Pelvic Floor Clinic between January 2004 and November 2008 were analysed. Patients were included if they had full thickness internal (grades 1-4 prolapse) or external RP (grade 5 prolapse). All those included were analysed with regards to the presence of an enterocoele. RESULTS: Three hundred and seventy-one patients [322 (87%) women and 49 (23%) men] were found to have a degree of RP. One out of eight (12.5%) patients with grade 1 RP, 10/42 (18.5%) with grade 2 RP, 34/125 (27%) with grade 3 RP, 62/135 (46%) with grade 4 RP and 23/49 (47%) with grade 5 full thickness external RP had an enterocoele present. This was a statistically significant trend (Pearson chi(2) test P < 0.0002). There was a significantly higher proportion of enterocoeles in women [125/322 (39%) than in men (5/49 (10%)] (P < 0.0001) and a higher likelihood of having an enterocoele with advancing age (P < 0.0001). Within the study, there was no significant difference in the proportion of nulliparous and parous women with enterocoeles (P = 0.8); there were a significantly higher proportion of enterocoeles in hysterectomized women (P = 0.015). CONCLUSIONS: Enterocoele is increasingly seen with advancing RP severity. This suggests that the two findings are part of the same pelvic floor process. These data support the hypothesis that enterocoele is a marker of severe pelvic floor weakness. Enterocoele is seen more frequently in females particularly after hysterectomy.

Catecholamine and cortisol levels during sleep in women with irritable bowel syndrome.

Evidence suggests that patients with irritable bowel syndrome (IBS) are hyper-responsive to environmental, physical and visceral stimuli. IBS patients also frequently report poor sleep quality. This study compared serum cortisol and plasma catecholamine levels during sleep between women with IBS (n = 30) and healthy controls (n = 31), and among subgroups within the IBS sample based on predominant stool patterns, IBS-diarrhoea (n = 14), IBS-constipation (n = 7) and IBS-alternators (n = 9). Cortisol was measured from serial blood samples drawn every 20 min, and catecholamines every hour, in a sleep laboratory from 8 pm until awakening. Because of the varied sleep schedules of the individual participants, each subject's hormone series time base was referenced with respect to their onset of Stage 2 sleep. Overall, there were no significant differences in cortisol or catecholamine patterns between women with IBS and controls, nor were there any group by time interactions. However, women with constipation-predominant IBS demonstrated significantly increased noradrenaline, adrenaline and cortisol levels throughout the sleep interval, and women with diarrhoea-predominant IBS were significantly lower on noradrenaline and cortisol. These results suggest that differences in neuroendocrine levels during sleep among IBS predominant bowel pattern subgroups may be greater than differences between IBS women and controls. Neuroendocrine profiles during sleep may contribute to our understanding of symptom expression in IBS.

Heart rate variability is related to pain severity and predominant bowel pattern in women with irritable bowel syndrome.

This study examined heart rate variability (HRV) in women with irritable bowel syndrome (IBS) to determine its association with gut pain and predominant bowel pattern. Women with IBS (constipation predominant n = 45, diarrhoea predominant n = 64, alternating n = 56) and healthy controls (n = 50) were recruited from the community. Severity of gut pain was measured retrospectively. The HRV (24 h) was summarized as high-frequency (HF) power and the ratio of low-frequency (LF) power to HF power. Among those women with IBS who have severe gut pain, the 15 constipation-predominant women had lower (P = 0.01) HF power and higher (P = 0.003) LF/HF ratio (geometric means 70 and 7.5, respectively) than the 21 women with diarrhoea-predominant IBS (286 and 3.1) and controls (224 and 3.9). In contrast, among women without severe pain, there is a smaller and not quite significant difference in the opposite direction. Using a broader definition of pain severity based on several questions nearly doubles the number of subjects in the severe pain group and shows even more significant results. The relationship of predominant bowel pattern to HRV is qualitatively different in the subgroup of patients with more severe pain than in the subgroup with less severe pain.

Effect of sacral neuromodulation for faecal incontinence on sexual activity.

INTRODUCTION: Faecal incontinence affects a percentage of the population and can have a significant effect on their ability to establish and maintain sexual relations. PATIENTS AND METHODS: Sixteen consecutive patients with permanent sacral neuromodulation (SNM) for faecal incontinence completed a 'Sex Life Questionnaire' at their follow up visit to ascertain whether there was any improvement in this aspect of their life. RESULTS: Nine of the sixteen patients was sexually active. These nine patients (median age 56 (35-61) years) had a significant reduction in faecal incontinence episodes per week from a median of 12 (1-55) to 1.5 (0-8.5) (P = 0.008). All nine patients reported that their sex life had been affected by feacal incontinence prior to SNM and seven had felt benefit from implantation. The median improvement in their sex life was 40% (1-100) and the percentage improvement was inversely correlated to age (r = -0.834, P = 0.005). CONCLUSION: SNM improves the quality of sexual activity in 78% of patients. More improvement seems to be gained the younger the patients.

Sacral nerve stimulation for faecal incontinence in patients with previous partial spinal injury including disc prolapse.

BACKGROUND: This study examined the use of sacral nerve stimulation (SNS) to treat faecal incontinence in patients with partial spinal injury. METHODS: Patients selected for SNS had experienced more than one episode of faecal incontinence per week to liquid or solid stool for more than 1 year and had failed maximal conservative treatment. All patients had an intact external anal sphincter. RESULTS: Temporary SNS was performed in 13 patients (median age 58.5 (range 39-73) years). The spinal insults were disc prolapse (six), trauma (four), spinal stenosis (one) or occurred during neurosurgery (two). Twelve patients (eight women and four men) had successful temporary stimulation and proceeded to permanent implantation. The median follow-up time was 12 (range 6-24) months. The mean(s.d.) number of episodes of incontinence decreased from 9.33(7.64) per week at baseline to 2.39(3.69) at last follow-up (P = 0.012). The number of days per week with incontinence and staining decreased significantly (both P < 0.001). Ability to defer defaecation improved from a median of not being able to defer (range 0-1 min) to being able to defer for 5-15 (range 0 to over 15) min (P = 0.022). CONCLUSION: SNS can benefit patients with faecal incontinence following partial spinal injury.

Systematic review of sacral nerve stimulation for faecal incontinence and constipation.

BACKGROUND AND METHOD: This systematic review assesses the efficacy and safety of sacral nerve stimulation (SNS) for faecal incontinence and constipation. Electronic databases and selected websites were searched for studies evaluating SNS in the treatment of faecal incontinence or constipation. Primary outcome measures included episodes of faecal incontinence per week (faecal incontinence studies) and number of evacuations per week (constipation studies). RESULTS: From 106 potentially relevant reports, six patient series and one crossover study of SNS for faecal incontinence, and four patient series and one crossover study of SNS for constipation, were included. After implantation, 41-75 per cent of patients achieved complete faecal continence and 75-100 per cent experienced improvement in episodes of incontinence. There were 19 adverse events among 149 patients. The small crossover study reported increased episodes of faecal incontinence when the implanted pulse generator was switched off. Case series of SNS for constipation reported an increased frequency of evacuation. There were four adverse events among the 20 patients with a permanent implant. The small crossover study reported a reduced number of evacuations when the pulse generator was switched off. CONCLUSION: SNS results in significant improvement in faecal incontinence in patients resistant to conservative treatment. Early data also suggest benefit in the treatment of constipation.

Sacral nerve stimulation for faecal incontinence in the UK.

BACKGROUND: Sacral nerve stimulation (SNS) is an effective therapy for faecal incontinence. Published studies derive largely from single centres and there is a need to determine the broader applicability of this procedure. METHODS: Prospective data were collected for all patients undergoing SNS in the UK. Records were reviewed to determine the outcome of treatment. RESULTS: In three UK centres 59 patients underwent peripheral nerve evaluation, with 46 (78 per cent) proceeding to permanent implantation. Of these 46 patients (40 women) all but two had improved continence at a median of 12 (range 1-72) months. Faecal incontinence improved from a median (range) of 7.5 (1-78) to 1 (0-39) episodes per week (P < 0.001). Urgency improved in all but five of 39 patients in whom ability to defer defaecation was determined, improving from a median of 1 (range 0-5) to 10 (range from 1 to more than 15) min (P < 0.001). Maximum anal squeeze pressure and sensory function to rectal distension changed significantly. Significant improvement occurred in general health (P = 0.024), mental health (P = 0.008), emotional role (P = 0.034), social function (P = 0.013) and vitality (P = 0.009) subscales of the Short Form 36 health survey questionnaire. There were no major complications. One implant was removed. CONCLUSION: SNS is a safe and effective treatment, in the medium to long term, for faecal incontinence when conservative treatment has failed.

Behavioural therapy (biofeedback) for solitary rectal ulcer syndrome improves symptoms and mucosal blood flow.

AIMS: The aim of the study was to determine if there is a permanent disorder of mucosal blood flow in patients with solitary rectal ulcer syndrome (SRUS) or a disorder related to autonomic gut innervation and physiological function that is reversible concomitant with successful treatment. Rectal mucosal blood flow was used as a validated measure of extrinsic autonomic nerve function. METHODS: Sixteen consecutive patients with SRUS (12 women; mean age 35 years) and 26 healthy controls (17 women; mean age 36 years) were studied. Laser Doppler mucosal flowmetry was performed before and after biofeedback treatment. Symptoms were documented before and after biofeedback treatment using a standardised prospectively applied questionnaire. RESULTS: Twelve of 16 patients (75%) reported subjective symptomatic improvement after treatment. Five of the 16 patients (31%) had sigmoidoscopic ulcer resolution. Pretreatment rectal mucosal blood flow was significantly lower in patients with SRUS compared with controls (163 (27) v 186 (14) flux units (FU) (mean (SD)); p<0.01). Biofeedback resulted in a significant improvement in rectal mucosal blood flow in subjects who felt subjectively better after biofeedback (p = 0.001), from 165 (30) FU to 190 (40) FU. CONCLUSION: Gut directed biofeedback is an effective behavioural treatment for the majority of patients with SRUS. Mucosal blood flow is reduced to a similar level seen in normal transit constipation, suggesting similar impaired extrinsic autonomic cholinergic nerve activity. Successful outcome following biofeedback is associated with increased rectal mucosal blood flow, suggesting that improved extrinsic innervation to the gut may be partially responsible for the response to treatment.

Direct access carpal tunnel surgery.

Carpal tunnel syndrome is a common condition and clinical diagnosis is often easily made. A system of direct referral for day-case carpal tunnel surgery was introduced. General practitioners, physicians and surgeons were advised of the service and the criteria for referral, which included female patients with bilateral symptoms and physical signs, and some response to conservative treatment. All patients were reviewed preoperatively by the senior author (GEBG). The service was an alternative to standard outpatient referral. A total of 51 patients was seen. Two were refused surgery. In all those who underwent surgery, the symptoms either resolved or were improved. The service was well received, although some patients felt that they were poorly informed preoperatively. The mean waiting time for surgery was reduced by four months and the patients avoided an outpatient appointment. Direct access day-case carpal tunnel surgery works well by reducing delays and the costs of treatment. Adequate patient information is important to make the best of the service.

Does a physically active lifestyle improve symptoms in women with irritable bowel syndrome?

It has been proposed that physical activity moderates physiological or psychological responses to chronic conditions. The purpose of this study was to determine if women with a chronic functional gastrointestinal (GI) disorder, irritable bowel syndrome, had less active lifestyles than healthy controls and to test whether active women with irritable bowel syndrome had less severe recalled or daily reports of GI, psychological, and somatic symptoms than inactive women with irritable bowel syndrome. Questionnaires were used to measure GI and psychological distress and somatic symptoms in 89 women who participated in this study. A daily symptom and activity diary was kept for one menstrual cycle. Women with irritable bowel syndrome were significantly less likely to be active (48%) than control women (71%) (X2 = 3.4, p = .05). Within the irritable bowel syndrome group, active women were less likely to report a feeling of incomplete evacuation following a bowel movement than inactive women (p < .04), yet active women did not have less severe recalled psychological or somatic symptoms than inactive women. Active women with irritable bowel syndrome reported less severe daily somatic symptoms, which were accounted for by a lower level of fatigue (p = .003), but not daily GI or psychological symptoms. These results suggest that physical activity may produce select symptom improvement in women with irritable bowel syndrome.

Effect of aerobic fitness on the physiological stress response in women.

Stress reactivity was assessed in aerobically fit (n = 14) and unfit (n = 8) females during the follicular phase of the menstrual cycle. Participants completed the Spielberger State-Trait Anxiety Inventory and provided a urine sample for catecholamine analysis before and after mental stress testing, Stroop Color-Word Test. Blood pressure, heart rate, muscle tension, and skin conductance were measured during mental stress testing. Fit and unfit participants differed significantly in baseline heart rate but not in stress reactivity or in state or trait anxiety. These data suggest that aerobic fitness does not attenuate the stress response in women prior to menopause.

Self-report and polysomnographic measures of sleep in women with irritable bowel syndrome.

BACKGROUND: Women who report chronic gastrointestinal symptoms compatible with a diagnosis of irritable bowel syndrome (IBS) frequently report sleep disturbances. OBJECTIVES: The purposes of this study were to (a) compare self-reported and polysomnographic indicators of sleep quality in women with IBS symptoms (IBS-SX, n= 16) and controls (n= 16); (b) examine the relationship between the indicators of sleep quality; and (c) determine the relationship between sleep indicators and psychological distress. METHOD: The women slept in a laboratory for 2 consecutive nights. Polysomnographic measurements were recorded during sleep, and a sleep questionnaire was completed upon awakening each morning. Psychological distress was measured with the Symptom Checklist-90-R during the initial interview. RESULTS: Women in the IBS-SX group reported significantly greater numbers of awakenings during sleep (p = .008) and had a longer latency to REM sleep (p = .04) than did the controls. Self-reported and polysomnographic indicators were more highly correlated in the control group than in the IBS-SX group. In the IBS-SX group, the greater the psychological distress, the less alert (rs = .419) and rested (rs = .564) the women felt in the morning and the more time the women spent in stages 3 and 4 sleep (rs = .479) and less in stage 2 (rs = -.447) and REM (rs = -.414) sleep. In the control group, psychological distress was not significantly associated with self-reported measures but was significantly associated with the number of awakenings (rs = .506) and time in stages 3 and 4 sleep (rs = -.677). CONCLUSIONS: Although the women in the IBS-SX group reported significantly more awakenings, the weak relationship between self-reported and polysomnographic indicators suggests that clinicians must keep in mind that further assessments may be necessary.