Female Irritable Bowel Syndrome Patients Research Articles

SPARC: Sex difference in colorectal afferent sensitization in zymosan‐induced visceral hypersensitivity as revealed by high‐throughput GCaMP recordings in thoracolumbar and lumbosacral DRG

Female patients with irritable bowel syndrome (IBS) report more intense visceral pain sensation than male patients. Female rats show more sensitive and cycle‐dependent visceromotor responses (VMR) to graded colorectal distension (CRD). Both clinical psychophysical evidence and preclinical behavioral data support an apparent sex difference in visceral nociception. However, very little is known regarding the potential differences in sensory neural encoding of distal colon and rectum (colorectum) between males and females. In this study, we systematically assessed the sex difference in colorectal neural encoding by conducting high‐throughput optical recordings in intact dorsal root ganglia (DRG) from control and visceral hypersensitive mice. We crossbred GCaMP6f mice with VGLUT2‐Cre mice to express GCamP6f gene in most colorectal sensory neurons. Mice receiving intracolonic treatment of zymosan (30mg/mL, 0.2mL) for three consecutive days developed behavioral visceral hypersensitivity as validated by enhanced VMR to CRD. We then harvested the colorectum with pelvic nerve, lumbar splanchnic nerve and T12 to S1 DRG in continuity in an ex vivo preparation for GCaMP6f recordings. A total of 2275 colorectal afferents were characterized from both sexes in control and zymosan‐treated groups. DRG neurons responding to either colorectal distension (15, 30, 45 and 60 mmHg) and/or mucosal shearing (20‐30 mL/min) were functionally categorized into four classes: mucosal, muscular‐mucosal and high‐ and low‐threshold muscular afferents. In control group, the number of colorectal afferents recorded per mouse were slightly lower in male mice than in female ones (38.7 vs. 45.2) with no significant difference in their distributions across thoracolumbar (TL) and lumbosacral (LS) DRG. In zymosan group, more afferents were recorded from each male mice than female ones (53.8 vs. 44.1) showing significantly higher TL innervation (T12, L1, and L2 DRG) in male group. Within the male groups, zymosan treatment resulted in a significant increase in the proportion of TL innervation as compared with saline treatment. In contrast, female mice showed no difference in the proportion of colorectal neurons between saline‐ and zymosan‐treated groups. Our results have revealed a significant sex difference in colorectal afferent innervation and sensitization in the context of behavioral visceral hypersensitivity. The current outcomes draw further focused research on the neurophysiological differences between sexes that could drive the differential gastrointestinal symptoms in male and female IBS patients.

Irritable Bowel Syndrome and the Menstrual Cycle.

Introduction: Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder. Female patients with bowel disease commonly report worsening of symptoms in the menstrual cycle. However, there is a paucity of data regarding IBS presentations' variation during different phases of the menstrual cycle. The current study aimed to evaluate the same in female IBS patients.Materials and Methods: Consecutive premenopausal female patients with the diagnosis of IBS attending the outdoor (OPD) of Department of Gastroenterology and Gynaecology; IMS and SUM Hospital, Bhubaneswar, Odisha from June 2019 to December 2019 were included in the study and evaluated by a set of questionnaires regarding various presentations during all the three phases of the menstrual cycle.Results: Consecutive 102 cases with the diagnosis of IBS were included in the study and evaluated. The mean age of presentation was in mid-30s. Most of the subjects suffered from IBS mixed (IBS-M) type. More patients significantly suffered from constipation (27.27%) during the luteal phase of their menstrual cycles than the menstrual period of their cycles (p - 0.009). More than 50% of all the cases suffered from abdominal bloating during all phases of the menstrual cycle, which was quite disturbing and affected the quality of life. These IBS patients were more symptomatic with more significant limitation of daily activities, suffered from low quality of life, and obtained physician consultation during the menstrual phase as compared to other cycle stages.Conclusion: Premenopausal female patients with IBS become much more symptomatic during the menstrual phase of the cycle than other stages of the cycle.

Eating disorders in patients with irritable bowel syndrome

IntroductionEating disorders (ED) constitute an important group of conditions that commonly occur in adolescents. Gastrointestinal complaints are frequently reported in ED patients. Few studies assessed the association of irritable bowel syndrome (IBS) with ED. The aim of the current study is to determine the prevalence of ED in a group of IBS patients and compare it with a healthy control group and assess the relationship of IBS sub-types, it's duration and severity with ED. Patients and methods100 IBS patients diagnosed according to the Rome-IV criteria and a control group consisting of 100 healthy adults, between 18 and 65 years old, were enrolled in this study. Sub-type, duration and severity of IBS were determined. All participants were requested to fill questionnaires to screen for ED. Results200 subjects participated in the study. 118(59%) were female and 92(41%) were male. The Eating Attitudes Test (EAT) score was significantly higher in the IBS group (Odds ratio: 5.3 CI 95%:4.3–9.3; p<0.001). The number of subjects with EAT score >30 was significantly higher in the IBS group (p<0.001). EAT scores were significantly higher in female IBS patients and in younger patients (p=0.013 and p=0.043; respectively). No significant association between the IBS sub-type and EAT score was found (p>0.05). However, IBS severity and duration positively correlated with EAT scores. DiscussionED should be considered in the management of IBS patients. Since many psychological factors can exacerbate IBS symptoms a multidisciplinary approach consisting of medical and behavioral therapeutic modalities should be employed for a better management of these patients.

Serum Levels of Chemerin, Apelin, and Adiponectin in Relation to Clinical Symptoms, Quality of Life, and Psychological Factors in Irritable Bowel Syndrome.

Adipokines have endocrine roles in metabolism and immunity. Dysregulation of adipokine levels is associated with several diseases with chronic inflammation. We aimed to assess the serum concentrations of chemerin, apelin, and adiponectin in irritable bowel syndrome (IBS). Furthermore, we evaluated the possible association of these adipokines with clinical symptoms, quality of life (QoL), and psychological factors. In this case-control study, 114 male and female IBS patients were recruited from outpatient clinics. Along with the IBS patients, 114 sex and age-matched healthy volunteers were recruited. Patients filled in the questionnaires of the IBS severity scoring system (IBSSS), gastrointestinal (GI) and somatic symptoms, IBS specific QoL (IBS-QoL), and psychological disorders, and went to the lab for blood sampling. Serum levels of both adiponectin and apelin were significantly (P=0.04, 0.03, respectively) lower, whereas chemerin was significantly (P=0.01) higher in IBS patients. Chemerin was higher in IBS-D compared with both IBS-C and IBS-A, while apelin and adiponectin were not different between subtypes. After adjustments for confounders only, chemerin had a positive association with IB severity scoring system and GI symptoms. Furthermore, chemerin had positive associations, whereas apelin and adiponectin had inverse associations with somatic symptoms and psychological factors. There were no significant associations between adipokines including chemerin, apelin, and adiponectin, and IBS-QoL. Chemerin had significant associations with both the severity of clinical symptoms and psychological factors in IBS; thus, it could be considered as a potential therapeutic target in these patients; however, further studies are needed.

Chronic Pelvic Pain and Irritable Bowel Syndrome: Is Subclinical Inflammation Bridging the Gap?

Irritable bowel syndrome (IBS) is characterized by a multitude of symptoms digestive and extra- digestive that need at some point a multidisciplinary approach. This study aimed at profiling IBS associated with chronic pelvic pain (CPP) in young females. A cross sectional observatory study on 40 consecutive young female patients (under 45 years) with IBS (Rome III) was performed. Patients were assigned in two groups, as matched pairs, based on the presence of chronic pelvic pain (CPP) symptoms: cystalgia, urinary urge and dyspareunia: CPP(+) vs. CPP(-) and undertook clinical examinations with special protocols related to migraine disability, fibromyalgia, temporo-mandibular joint dysfunction, as well as assessment of anxiety and severity of abdominal pain. Laboratory work-up (blood, urine and stool) as well as multiple exams: digestive endoscopy, abdominal and pelvic ultrasound//CT were performed. Results: CPP (+) group displayed higher CRP, TNF-alpha, gut dysbiosis (DB) and abdominal pain severity, as well as associated fibromyalgia, migraine and anxiety mood disorder. DB positively correlated with inflammatory markers and symptoms characterizing CPP. In conclusion, young female IBS patients with concurrent CPP symptoms often experienced other associated functional pain conditions like FM and migraine along with anxiety, more severe abdominal complaints as well as higher gut DB and consecutively subclinical pro-inflammatory status. Strong positive correlations of gut DB to inflammatory markers as well as to CPP symptoms give the relationship IBS-CPP a new perspective.

Chronic Pelvic Pain and Irritable Bowel Syndrome: Is Subclinical Inflammation Bridging the Gap?

Irritable bowel syndrome (IBS) is characterized by a multitude of symptoms digestive and extra- digestive that need at some point a multidisciplinary approach. This study aimed at profiling IBS associated with chronic pelvic pain (CPP) in young females. A cross sectional observatory study on 40 consecutive young female patients (under 45 years) with IBS (Rome III) was performed. Patients were assigned in two groups, as matched pairs, based on the presence of chronic pelvic pain (CPP) symptoms: cystalgia, urinary urge and dyspareunia: CPP(+) vs. CPP(-) and undertook clinical examinations with special protocols related to migraine disability, fibromyalgia, temporo-mandibular joint dysfunction, as well as assessment of anxiety and severity of abdominal pain. Laboratory work-up (blood, urine and stool) as well as multiple exams: digestive endoscopy, abdominal and pelvic ultrasound//CT were performed. Results: CPP (+) group displayed higher CRP, TNF-alpha, gut dysbiosis (DB) and abdominal pain severity, as well as associated fibromyalgia, migraine and anxiety mood disorder. DB positively correlated with inflammatory markers and symptoms characterizing CPP. In conclusion, young female IBS patients with concurrent CPP symptoms often experienced other associated functional pain conditions like FM and migraine along with anxiety, more severe abdominal complaints as well as higher gut DB and consecutively subclinical pro-inflammatory status. Strong positive correlations of gut DB to inflammatory markers as well as to CPP symptoms give the relationship IBS-CPP a new perspective. Keywords: CPP, IBS, inflammation, gut dysbiosis

5-HT3 receptor signaling in serotonin transporter-knockout rats: a female sex-specific animal model of visceral hypersensitivity

The irritable bowel syndrome (IBS) is a functional gastrointestinal motor and visceral sensation disorder that is more common in women than men. Female serotonin transporter (SERT)-gene knockout (KO) rats exhibit hypersensitivity to colorectal balloon distention (CRD) that mimics colonic hypersensitivity occurring in female IBS patients. Alosetron (5-HT3 receptor antagonist) is used to treat diarrhea-predominant IBS in female patients. Other 5-HT3 receptor antagonists are ineffective at treating IBS symptoms. The visceromotor response (VMR) to CRD in SERT-KO and wild-type (WT) rats was measured following subcutaneous (sc), intracerobroventricular (icv), or intrathecal (it) treatment with 5-HT3 receptor antagonists and an agonist. Alosetron (sc) and granisetron (antagonists) caused a paradoxical increase in the VMR to CRD in SERT-KO female rats. Alosetron (sc) increased the VMR to CRD in WT male rats. Alosetron (it) increased the VMR to CRD in SERT-KO female rats only, and the 5-HT3 receptor agonist SR-52772 increased the VMR to CRD in SERT-KO male rats. Depletion of spinal 5-HT using 5,7-dihydroxytryptamine prevented the increase in VMR to CRD in SERT-KO female and male rats treated it with alosetron and SR-52772, respectively. Alosetron (icv) did not affect the VMR to CRD in WT or KO female rats, but it increased the VMR in male SERT-KO but not WT male rats. These data suggest that 5-HT3 receptor signaling at the dorsal spinal cord mediates visceral hypersensitivity in female SERT-KO rats. Such differences could facilitate development of sex-specific drug treatments for visceral pain. NEW & NOTEWORTHY We studied a model of female sex-specific visceral hypersensitivity using rats that had a loss of function of the serotonin transporter (SERT) caused by gene truncation. Female SERT-KO rats exhibited visceral hypersensitivity in response to colorectal balloon distention. We found that increased 5-HT signaling at dorsal spine 5-HT3 receptors was responsible for visceral hypersensitivity in female but not male SERT-KO rats.

Low-FODMAP vs regular rye bread in irritable bowel syndrome: Randomized SmartPill® study.

AIMTo compare the effects of regular vs low-FODMAP rye bread on irritable bowel syndrome (IBS) symptoms and to study gastrointestinal conditions with SmartPill®.METHODSOur aim was to evaluate if rye bread low in FODMAPs would cause reduced hydrogen excretion, lower intraluminal pressure, higher colonic pH, different transit times, and fewer IBS symptoms than regular rye bread. The study was a randomized, double-blind, controlled cross-over meal study. Female IBS patients (n = 7) ate study breads at three consecutive meals during one day. The diet was similar for both study periods except for the FODMAP content of the bread consumed during the study day. Intraluminal pH, transit time, and pressure were measured by SmartPill, an indigestible motility capsule.RESULTSHydrogen excretion (a marker of colonic fermentation) expressed as area under the curve (AUC)(0-630 min) was [median (range)] 6300 (1785-10800) ppm∙min for low-FODMAP rye bread and 10 635 (4215-13080) ppm∙min for regular bread (P = 0.028). Mean scores of gastrointestinal symptoms showed no statistically significant differences but suggested less flatulence after low-FODMAP bread consumption (P = 0.063). Intraluminal pressure correlated significantly with total symptom score after regular rye bread (ρ = 0.786, P = 0.036) and nearly significantly after low-FODMAP bread consumption (ρ = 0.75, P = 0.052). We found no differences in pH, pressure, or transit times between the breads. Gastric residence of SmartPill was slower than expected. SmartPill left the stomach in less than 5 h only during one measurement (out of 14 measurements in total) and therefore did not follow on par with the rye bread bolus.CONCLUSIONLow-FODMAP rye bread reduced colonic fermentation vs regular rye bread. No difference was found in median values of intraluminal conditions of the gastrointestinal tract.

Sexual Abuse Is Associated With an Abnormal Psychological Profile and Sleep Difficulty in Patients With Irritable Bowel Syndrome in Taiwan.

Background/AimsBoth sexual and physical abuse history have been reported to be associated with irritable bowel syndrome (IBS) in Western countries. The impact of abuse history in IBS patients in Asia remains unclear. We aim to determine the prevalence of abuse history, its associated psychological profiles, and sleep problems among IBS patients in Taiwan.MethodsIn total, 194 Rome III-defined IBS patients were invited to participate. Age- and sex-matched healthy carriers of chronic hepatitis B or hepatitis C without chronic abdominal symptoms were identified as disease-controls. We administered a validated questionnaire to evaluate bowel symptoms, physical/sexual abuse history, anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and sleep quality.ResultsIBS patients had a significantly higher prevalence of sexual abuse history than the disease-control group both before (16.5% vs 6.7%, P < 0.05) and after (16.0% vs 6.6%, P < 0.05) adolescence. These significant differences were mainly observed in women (13.4% vs 3.4%, P < 0.05). No difference was noted in history of physical abuse between the 2 groups. IBS patients with a history of sexual abuse had significantly higher HADS scores and higher frequencies of sleep difficulty than those without.ConclusionsIn Taiwan, sexual abuse history was more prevalent in female IBS patients than controls. Sexual abuse history may contribute to higher anxiety/depression levels and sleep difficulties, which are commonly experienced in IBS patients. In Asia, abuse history should be obtained when approaching IBS patients to facilitate better management.

5‐HT 3 Receptor Signaling in a Rat Model of Sex Specific Visceral Hypersensitivity

Background Irritable bowel syndrome (IBS) is a functional gastrointestinal motor and visceral sensation disorder that is more prominent in women compared to men. 5-Hydroxytryptamine (5-HT, serotonin) signaling is disrupted in some IBS patients possibly due to polymorphic variations in the gene encoding the serotonin transporter (SERT) which result in increased extracellular 5-HT availability. Female SERT knockout (KO) rats exhibit visceral hypersensitivity to colonic distention that mimics colonic hypersensitivity known to occur in female IBS patients. Objective. We tested the hypothesis that 5-HT action at 5-HT3 receptors contributes to visceral hypersensitivity. Methods. We examined the effects of acute administration of morphine and the 5-HT3 receptor antagonists alosetron, granisetron, and ondansetron on visceral sensitivity in SERT KO and wild type (WT) rats. We measured the visceromotor response (VMR) to colorectal distension (CRD). Results. Ondansetron (0.1 mg/kg, s.c) did not affect visceral sensitivity, while alosetron (0.1 mg/kg, s.c.) increased the VMR to CRD in SERT KO female rats and WT male rats. Granisetron (0.1 mg/kg, s.c.) increased VMR to CRD in SERT KO female rats only. Morphine (3 mg/kg s.c.) suppressed the VMR to CRD in all rats. Conclusions The results suggest that acute peripheral administration of some 5-HT3 receptor antagonists causes a paradoxical increase in the VMR to CRD. 5-HT3 receptor antagonists may interact with ascending pain pathways and descending pain inhibitory pathways. Supported by: 5R21NS075841

Ovariectomy reduces Visceral Hypersensitivity in Female Serotonin Transporter (SERT) Knockout (KO) Rats

Visceral hypersensitivity (VH) is a symptom in irritable bowel syndrome (IBS), particularly in women and symptom severity varies over the menstrual cycle. Disrupted serotonin signaling, including reduced SERT expression, occurs in some IBS patients. We studied VH in male and female SERT KO and wild type (WT) rats to determine if SERT deficiency and the estrous cycle were associated with VH.MethodsVH was measured using the abdominal electromyographic visceromotor response (VMR) to colorectal balloon distention (CRD). We also assessed somatic hypersensitivity using the hot plate test. Ovariectomized (OVX) SERT KO and WT rats were used to investigate the effects of gonadal hormones on VH.ResultsThe VMR to CRD was increased in female but not male SERT KO rats (P&lt;0.05); the maximum response occurred during proestrus. The VMR was greater in female SERT KO vs. female WT rats. OVX reduced VH in female SERT KO rats (P&lt;0.05). There were no differences in somatic thermal sensitivity between female WT and SERT KO rats.ConclusionsThere is an interaction between increased serotonin availability (as occurs in SERT KO rats) and female gonadal hormones that results in VH. This mimics symptoms occurring in female IBS patients. The SERT KO rat may be a useful model for mechanistic studies of interactions between sex, serotonin and visceral sensation.

Therapeutic mechanisms of a mindfulness-based treatment for IBS: effects on visceral sensitivity, catastrophizing, and affective processing of pain sensations.

Irritable bowel syndrome (IBS) is a prevalent functional disorder characterized by abdominal pain and hypervigilance to gastrointestinal sensations. We hypothesized that mindfulness training (MT), which promotes nonreactive awareness of emotional and sensory experience, may target underlying mechanisms of IBS including affective pain processing and catastrophic appraisals of gastrointestinal sensations. Seventy five female IBS patients were randomly assigned to participate in either 8weeks of MT or a social support group. A theoretically grounded, multivariate path model tested therapeutic mediators of the effect of MT on IBS severity and quality of life. Results suggest that MT exerts significant therapeutic effects on IBS symptoms by promoting nonreactivity to gut-focused anxiety and catastrophic appraisals of the significance of abdominal sensations coupled with a refocusing of attention onto interoceptive data with less emotional interference. Hence, MT appears to target and ameliorate the underlying pathogenic mechanisms of IBS.

Influence of gender and psychosocial parameters on the quality of life in patients with irritable bowel syndrome

Objective To investigate the influence of gender and psychosocial parameters on the quality of life in patients with irritable bowel syndrome(IBS). Methods Out-patients from Jan to Oct 2008 in the Department of Gastroenterology at the First Affiliated Hospital of Nanjing Medical University were enrolled. Based on Rome teria IBS was diagnosed. Interviewed by a GI physician with questionnaire of demographic data,Zung self-rating anxiety and depression scale(SAS/SDS) and IBS-specific quality of life(IBS-QOL) questionnaire. Results 452 patients were diagnosed as IBS according to Rome Ⅲ criteria. IBS was more common in female. In male, anxiety and depression scales were significantly increased( t =7. 191、6. 459 ,P ＜ 0. 01 ) and the scale of IBS-QOL was significantly decreased ( t =9.119, P ＜ 0.01 ) in female IBS patients. In IBS patients, IBS-QOL scales were negatively associated with the anxiety and depression scales(P ＜0. 01 ). Conclusion These results suggest that there were gender differences in psychological status and quality of life in IBS patients,and difference psychological status based on gender should influence the quality of life of patients with IBS. Key words: Irritable bowel syndrome; Gender; Psychology; Quality of life

Rome III Criteria for Functional Gastrointestinal Disorders: Is There a Need for a Better Definition?

Rome III Criteria for Functional Gastrointestinal Disorders: Is There a Need for a Better Definition?

Mindfulness Training Reduces the Severity of Irritable Bowel Syndrome in Women: Results of a Randomized Controlled Trial

This prospective, randomized controlled trial explored the feasibility and efficacy of a group program of mindfulness training, a cognitive-behavioral technique, for women with irritable bowel syndrome (IBS). The technique involves training in intentionally attending to present-moment experience and non-judgmental awareness of body sensations and emotions. Seventy-five female IBS patients were randomly assigned to eight weekly and one half-day intensive sessions of either mindfulness group (MG) training or a support group (SG). Participants completed the IBS severity scale (primary outcome), IBS-quality of life, brief symptom inventory-18, visceral sensitivity index, treatment credibility scale, and five-facet mindfulness questionnaire before and after treatment and at 3-month follow-up. Women in the MG showed greater reductions in IBS symptom severity immediately after training (26.4% vs. 6.2% reduction; P=0.006) and at 3-month follow-up (38.2% vs. 11.8%; P=0.001) relative to SG. Changes in quality of life, psychological distress, and visceral anxiety were not significantly different between groups immediately after treatment, but evidenced significantly greater improvements in the MG than in the SG at the 3-month follow-up. Mindfulness scores increased significantly more in the MG after treatment, confirming effective learning of mindfulness skills. Participants' ratings of the credibility of their assigned interventions, measured after the first group session, were not different between groups. This randomized controlled trial demonstrated that mindfulness training has a substantial therapeutic effect on bowel symptom severity, improves health-related quality of life, and reduces distress. The beneficial effects persist for at least 3 months after group training.

Gender Differences in Motility of the Large and Small Intestine in Patients With IBS

Background: Visceral hypersensitivity, and altered gastrointestinal motility and secretion, are considered to be key pathophysiological factors in irritable bowel syndrome (IBS), and of great importance for symptom generation. The symptom pattern differs between female and male IBS patients , with more severe abdominal pain, bloating and constipation in females (Khatai et al. DDW 2010). Whether this can be explained by gender differences in pathophysiological alterations is incompletely understood. Aim: To evaluate potential gender differences in small intestinal motility and secretion, colonic motility and rectal sensorimotor function in patients with IBS. Methods: We included 36 male and 36 female IBS patients, matched for age (mean age 39 (20-64) years), who fulfilled the ROME II criteria. All patients underwent investigations to assess colonic motility (colonic transit time using radiopaque markers), small intestinal motility and secretion (antroduodenojejunal manometry with jejunal transmural potential difference (PD) measurement in the fasting state (3h) and after meal intake (1h)) and rectal sensorimotor function (rectal balloon distensions before and after meal intake; 800kcal; 60% fat). Results: Colonic transit time differed between female and male IBS patients, with slower transit in females (2.1±1.3 (mean±SD) vs. 1.2±0.8 days; p<0.0001). Differences were also found in the small intestinal motility with slower propagation velocity of phase III in females (8.7±4.5 vs. 15±9.4 cm/min; p<0.01), and a tendency towards shorter duration of phase III in females (p<0.1). The motility indices in the jejunum also tended to be lower in female versus male IBS patients, but this only reached statistical significance in the fasting state (last 30 min of phase II) (3310±1040 vs. 4510±2730 mmHg x sec; p<0.05). No gender differences were seen in PD measurements in the small intestine, reflecting chloride secretion, or in rectal compliance, tone or sensitivity. Conclusion: We have demonstrated gender differences in small and large intestinal motility in IBS patients, but not in small intestinal secretion or rectal sensorimotor function. These findings are of potential importance for observed differences in the symptom pattern between male and female IBS patients.

Sex-related differences in prepulse inhibition of startle in irritable bowel syndrome (IBS).

Alterations in central networks involved in the regulation of arousal, attention, and cognition may be critical for irritable bowel syndrome (IBS) symptom maintenance and exacerbation. Differential sensitivities in these networks may underlie sex differences noted in IBS. The current study examined prepulse inhibition (PPI), a measure of sensorimotor gating, in male and female IBS patients. Relationships between PPI and symptom severity were examined, as well as potential menstrual status effects. Compared to healthy controls, male IBS patients had significantly reduced PPI; whereas female IBS patients (particularly naturally cycling women) had significantly enhanced PPI suggesting hypervigilance. Considering previously demonstrated sex-related differences in perceptual and brain imaging findings in IBS patients, the current findings suggest that different neurobiological mechanisms underlie symptom presentation in male and female IBS patients. Compromised filtering of information in male IBS patients may be due to compromised top down (prefrontal, midcingulate) control mechanisms while increased attention to threat due to increased limbic and paralimbic circuits may be characteristic of female IBS patients.

Serotonin transporter activity and serotonin concentration in platelets of patients with irritable bowel syndrome: effect of gender

In the past decade, a strong argument has been built for the role of serotonin (5HT) and the serotonin transporter (SERT) in irritable bowel syndrome (IBS). However, it is still not clear how SERT contributes to this clinically heterogeneous disease. The present study addressed this issue by implementing platelet (plt) markers of SERT activity in the assessment protocol. Fasting blood samples of 149 (51 male/98 female) subjects with Rome II and III defined IBS subtypes, and 163 healthy control subjects (CSs; 75 male/88 female) were analyzed for platelet 5HT concentration and 5HT uptake activity [maximum uptake rate (V (max)) and affinity constant (K (m))]. Gender had a significant impact on platelet markers of SERT activity. Male IBS patients showed significantly lower median V (max) and K (m) values than the male CS (V (max) 1.706 vs. 2.148 nmol/10(9) plts x min, P < 0.001; K (m) 346 vs. 410 nmol, P = 0.008) without any significant reduction in platelet 5HT concentration (362 vs. 394 ng/10(9) plts). On the other hand, V (max) values were not different between female IBS patients and female CS (1.642 vs. 1.741 nmol/10(9) plts x min), but platelet 5HT concentration was significantly lower in females with diarrhea-predominant IBS (363 vs. 435 ng/10(9) plts, P < 0.05). Although an absolute extrapolation from platelets to the gastrointestinal tissue does not appear to be justified, our findings demonstrated that the contribution of disturbed SERT activity to IBS is not uniform and is possibly gender-specific. The results suggest that an assessment of SERT function in platelets may help to elucidate the differences between IBS patients in response to drugs affecting the 5HT system.

Mucosal Immune Activation in Irritable Bowel Syndrome: Gender-Dependence and Association With Digestive Symptoms

Immune activation may be involved in the pathogenesis of irritable bowel syndrome (IBS). However, the relative magnitude of this immune component and its correlation with gender and gastrointestinal complaints in IBS patients remains poorly elucidated. We enrolled 48 IBS patients, with either diarrhea or constipation, 12 patients with microscopic colitis, 20 patients with ulcerative colitis, and 24 healthy controls. Colonic immunocytes were identified with quantitative immunohistochemistry on mucosal biopsies. Gastrointestinal symptoms were assessed using a validated questionnaire. IBS patients showed a significant 72% increase in mucosal immune cells compared to controls (P<0.001). Further analyses showed that increased immune cells were present in 50% of the IBS patients. The magnitude of the immune infiltrate in IBS was significantly lower than that of microscopic colitis or ulcerative colitis (42% and 124% increases vs. IBS, respectively; P<0.001). Compared with controls, IBS patients had increased numbers of CD3+, CD4+, and CD8+ T cells and mast cells (P<0.001). Compared to male IBS patients, female IBS patients had greater numbers of mast cells (P=0.066), but lower numbers of CD3+ and CD8+ T cells (P=0.002 and <0.001, respectively). Mucosal mast cell infiltration of IBS patients was significantly associated with abdominal bloating frequency (P=0.022) and with symptoms of dysmotility-like dyspepsia (P=0.001), but not ulcer-like dyspepsia. A large subset of IBS patients shows gender-dependent mucosal infiltration of immunocytes that correlates with abdominal bloating and dysmotility-like dyspepsia. These results provide the rationale for considering immune mechanisms as a pathophysiological component in a subset of IBS patients.

Further Validation of the IBS-QOL: Female Mexican IBS Patients Have Poorer Quality of Life Than Females from North Carolina

The Irritable Bowel Syndrome (IBS)-Quality of Life (QOL) is the most extensively validated health-related quality of life (HRQOL)-specific instrument for IBS with appropriate evidence for psychometric validity. Our aim was to linguistically validate the IBS-QOL for Mexico according to standard guidelines, to conduct further psychometric validation, and to compare the HRQOL between IBS patients from Mexico and North Carolina (University of North Carolina). Construct validity was tested by correlating scores from the Mexican Spanish IBS-QOL with those for anxiety and depression obtained by the Hospital Anxiety and Depression scale. Also, HRQOL from Rome I female IBS patients who consulted a tertiary referral center in Mexico was compared with that of female patients from UNC matched by age and bowel habit. A general univariate linear model was done to determine the most important variable over HRQOL, place of origin, or bowel habit. The majority of the IBS-QOL items had a negative correlation with depression as well as with anxiety. Compared to patients from UNC, the Mexican ones reported significant lower scores on Body Image and Health Worry and a trend in Interference with activities and in the Overall score. There were some differences in Dysphoria and Interference that were related to bowel habit, independently of the place of origin. In conclusion, the IBS-QOL validated in Mexican Spanish has shown construct validity. Using this instrument we found that female IBS patients who consulted a tertiary referral center in Mexico have lower HRQOL than those in North Carolina at least in factors such as Body Image and Health Worry.