Relationships of Microbiome Markers With Extraintestinal, Psychological Distress and Gastrointestinal Symptoms, and Quality of Life in Women With Irritable Bowel Syndrome.

INTRODUCTION: Altered microbial diversity has been associated with gastrointestinal (GI) symptoms in persons with irritable bowel syndrome (IBS). Less is known about the relationship of microbiome with extraintestinal pain and psychological distress symptoms and quality of life (QOL) in persons with IBS. We aimed to evaluate the relationship of fecal microbiota to GI symptoms, stool consistency, psychological distress, extraintestinal pain, and QOL in participants meeting Rome III criteria for IBS. METHODS: Seventy-six women completed a 28-day diary that included GI, stool consistency, psychological distress, and extraintestinal pain ratings. Participants completed the IBS-Specific Quality of Life questionnaire. Stool samples were collected and analyzed by 16S rRNA gene sequencing. Principal component analysis was performed and the first 2 components (PC1, PC2) were used to test relationships among bacterial families and clinical measures. RESULTS: Participants were categorized as IBS constipation (n=22), IBS diarrhea (n=39), IBS mixed (n=13), and IBS unsubtyped (n=2). There was a significant group effect for the Firmicutes to Bacteroidetes ratio and PC1. Lower microbial diversity and richness were associated with increased urgency and extraintestinal pain, worse QOL, and looser stools. Lower extraintestinal pain was associated with increased Rikenellaceae, Christensenellaceae, Dehalobabacteriaceae, Oscillospiraceae, Mogibacteriaceae, Ruminococcaceae, Sutterellaceae, Desulfovibrionaceae, and Erysipelotrichaceae abundances. QOL was positively associated with many of these same bacterial families. Higher Firmicutes to Bacteroidetes ratio was positively associated with loose stools. There were no statistically significant relationships between daily psychological distress or abdominal pain and bacterial families. CONCLUSIONS: Stool microbial diversity and composition are linked to daily extraintestinal symptoms, stool consistency, and QOL in women with IBS.

Relationships Between Abdominal Pain and Fatigue With Psychological Distress as a Mediator in Women With Irritable Bowel Syndrome.

Women with irritable bowel syndrome often report fatigue, along with abdominal pain and psychological distress (i.e., depression and anxiety). There is little information about the relationships among these symptoms. Using a secondary data analysis (N = 356), we examined the relationship between abdominal pain and fatigue and whether psychological distress mediates the effect of abdominal pain on fatigue in both across women and within woman with irritable bowel syndrome. Data gathered through a 28-day diary were analyzed with linear regressions. The across-women and within-woman relationships among same-day abdominal pain, fatigue, and psychological distress were examined. Within-woman relationships were also examined for directionality among symptoms (i.e., prior-day abdominal pain predicts next-day fatigue and prior-day fatigue predicts next-day abdominal pain). In across-women and within-woman analyses on the same day, abdominal pain and fatigue were positively correlated. In within-woman analyses, abdominal pain predicted next-day fatigue, but fatigue did not predict next-day pain. In across-women and within-woman analyses, psychological distress partially mediated the effects of abdominal pain on fatigue. Symptom management incorporating strategies to decrease both abdominal pain and psychological distress are likely to reduce fatigue. Nursing interventions, such as self-management skills to reduce abdominal pain and psychological distress, may have the added benefit of reducing fatigue in irritable bowel syndrome.

Symptom-based latent classes of persons with irritable bowel syndrome.

A large amount of interindividual variability exists in symptom experiences of persons with irritable bowel syndrome (IBS). Thus, consideration of multiple symptoms to identify distinct symptom subgroups may be useful in directing personalized health strategies for symptom management. We aimed to identify latent classes (i.e., subgroups) of persons with IBS who share similar patterns of symptoms using symptom-related variables (six groups of daily diary symptoms, cognitive beliefs about IBS, and IBS quality of life [QOL]); and to examine how subgroups differed in patient characteristics. Data were derived from a baseline assessment of men and women enrolled in two cognitively-focused intervention trials (N = 332). Using latent class analysis, four latent classes were identified: Class 1 (low symptoms and good QOL, n = 153), Class 2 (low symptoms and moderate QOL, n = 106), Class 3 (high symptoms with diarrhea and poor QOL, n = 38), and Class 4 (high symptoms with low diarrhea and moderate QOL, n = 35). Diarrhea, being female, less formal education, unemployment, and previous history of major depressive disorder were associated with membership in Class 3. Using these distinct symptom profiles, the next step is to explore underlying mechanisms accounting for symptom burden with the goal of designing tailored interventions to reduce that burden.

Symptom Comparisons Between Asian American and White American Women With Irritable Bowel Syndrome.

There is little information on racial/ethnic characteristics of patients with irritable bowel syndrome. In this study, we determined whether the severity of symptoms (gastrointestinal, psychological distress), cognitive beliefs about irritable bowel syndrome, and life impacts (life interference, health-related quality of life) differ between Asian American and White American women with irritable bowel syndrome. We also look at the relationships among these variables. Asian American women (N = 21) and age- and design-matched White American women (N = 63) with irritable bowel syndrome were included. Data were collected from questionnaires and a 28-day daily diary (e.g., abdominal pain, depression). The percent of days with moderate/severe abdominal pain and psychological distress were significantly higher, and constipation- and diarrhea-dominant bowel pattern subtypes were prevalent in White Americans as compared with Asian Americans. Positive relationships of gastrointestinal symptoms with psychological distress, and of gastrointestinal and psychological symptoms with negative cognitive beliefs and negative life impact, were observed in White Americans. Further studies to evaluate contributing (e.g., cultural-environmental, pathophysiological, diet) factors of symptom characteristics in Asian Americans are suggested. Our study provides useful information for healthcare providers to understand symptoms and cultural factors and the potential for culturally tailored symptom management for this patient group.

COMT Val158Met Polymorphism and Symptom Improvement Following a Cognitively Focused Intervention for Irritable Bowel Syndrome.

BACKGROUND: Our nurse-delivered comprehensive self-management (CSM) program, a cognitive behavioral therapy intervention, is effective in reducing gastrointestinal and psychological distress symptoms in patients with irritable bowel syndrome (IBS). Findings from non-IBS studies indicate that the catechol-O-methyltransferase (COMT) Val158Met polymorphism may moderate the efficacy of cognitive behavioral therapy. It is unknown whether this COMT polymorphism is associated with symptom improvements in patients with IBS. OBJECTIVE: We tested whether this COMT Val158Met polymorphism influences the efficacy of our 2-month CSM intervention. METHODS: We analyzed data from two published randomized controlled trials of CSM. The combined European American sample included 149 women and 23 men with IBS (CSM, n = 111; usual care [UC], n = 61). The primary outcomes were daily reports of abdominal pain, depression, anxiety, and feeling stressed measured 3 and 6 months after randomization. Secondary outcomes were additional daily symptoms, retrospective psychological distress, IBS quality of life, and cognitive beliefs about IBS. The interaction between COMT Val158Met polymorphism and treatment group (CSM vs. UC) in a generalized estimating equation model tested the main objective. RESULTS: At 3 months, participants with at least one Val allele benefited more from CSM than did those with the Met/Met genotype (p = .01 for anxiety and feeling stressed, and p < .16 for abdominal pain and depression). The moderating effect of genotype was weaker at 6 months. DISCUSSION: Persons with at least one Val allele may benefit more from CSM than those homozygous for the Met allele. Future studies with larger and more racially diverse samples are needed to confirm these findings. RCT REGISTRATION: Parent studies were registered at ClinicalTrials.gov (NCT00167635 and NCT00907790).

A Comprehensive Self-Management Irritable Bowel Syndrome Program Produces Sustainable Changes in Behavior After 1 Year.

BACKGROUND & AIMS: We developed a comprehensive self-management (CSM) program that combines cognitive behavioral therapy with relaxation and dietary strategies; 9 sessions (1 hour each) over 13 weeks were shown to reduce gastrointestinal symptoms and increase quality of life in a randomized trial of patients with irritable bowel syndrome (IBS), compared with usual care. The aims of this study were to describe strategies patients with IBS selected and continued to use, 12 months after the CSM program began. METHODS: We performed a cohort study to continue to follow 81 adults with IBS (87% female; mean age, 45 ± 15 years old) who received the CSM program in the previous clinical trial. During the last CSM session, participants selected strategies they intended to continue using to manage their IBS. CSM strategies were categorized into subthemes of diet (composition, trigger foods, meal size or timing, and eating behaviors), relaxation (specific relaxation strategies and lifestyle behaviors), and alternative thoughts (identifying thought distortions, challenging underlying beliefs, and other strategies). Twelve months later, participants were asked how often they used each strategy (not at all or rarely, occasionally, often, very often, or almost always). RESULTS: At the last CSM session, 95% of the patients selected the subthemes of specific relaxation strategies, 90% selected diet composition, and 90% identified thought distortions for continued use. At 12 months, 94% of the participants (76 of 81) were still using at least 6 strategies, and adherence was greater than 79% for all subthemes. CONCLUSIONS: We developed a CSM program to reduce symptoms and increase quality of life in patients with IBS that produced sustainable behavioral changes in almost all patients (94%) after 1 year of follow-up.

Fatigue Measures in Noncancer Gastrointestinal Disorders: A Critical Review.

Fatigue is commonly reported by patients with noncancer gastrointestinal (GI) disorders such as organic and functional GI disorders. This critical review was conducted to evaluate fatigue measures that have been used in these patients. A systematic search using six databases (PubMed, PsycINFO, EMBASE, CINAHL, ProQuest, and Cochrane Review) was conducted from January 2000 to June 2014, and evaluations and reviews of fatigue instruments were performed by two independent reviewers (author and medical librarian). Fourteen instruments from 25 studies were identified. Ten instruments were solely focused on fatigue and four were multisymptom instruments. The average quality score of the 14 instruments was 10.7 (range, 6-14) out of 14. There were five instruments with high overall scores based on usability/feasibility, clinical/research utility, and psychometric properties (3 fatigue-specific and 2 multisymptom). There are valid and reliable measures that are currently available to assess fatigue in noncancer GI patients. Utilization of these common measures may assist clinicians (GI healthcare providers) and researchers to better understand the impact of fatigue in these patients. The instruments with low-quality scores cannot be chosen for routine use without further validation.

Anxiety, depression, and catecholamine levels after self-management intervention in irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) often report higher levels of psychological distress, specifically anxiety, and depression than non-IBS patients. The management of gastrointestinal symptoms and psychological distress is demonstrably amenable to cognitive-behavioral therapies in a significant number of patients with IBS. The present secondary analysis evaluates the impact of nurse-delivered self-management interventions on anxiety, depression, and urine catecholamine levels in adult IBS patients. Participants in the study were randomized to 2 intervention groups of either comprehensive self-management (CSM) intervention or usual care control. Daily diary ratings of gastrointestinal symptoms, anxiety, and depression were recorded every evening for 28 days during the baseline period and subsequently at 3, 6, and 12 months postrandomization. Catecholamine levels of epinephrine and norepinephrine were measured from 4 weekly 1st morning urine samples at baseline as well as at each follow-up time. The CSM group reported significantly lower levels of anxiety and depression at follow-up than the usual care group (p = .018 and .021, respectively). In contrast, urine catecholamine levels displayed no appreciable change. Thus, although nurse-delivered CSM interventions showed no impact on urinary catecholamine levels, daily psychological distress was measurably reduced.

Relationship between patterns of alcohol consumption and gastrointestinal symptoms among patients with irritable bowel syndrome.

OBJECTIVES: Heavy alcohol intake may exacerbate gastrointestinal (GI) symptoms in adults with irritable bowel syndrome (IBS); however, the role of alcohol in IBS is unclear. We investigated prospective associations between daily patterns of alcohol intake and next day's GI symptoms using daily diaries. METHODS: In an observational study of women aged 18-48 years with IBS and healthy controls, participants recorded daily GI symptoms, alcohol intake, caffeine intake, and cigarette smoking for ≈ 1 month. GI symptoms included abdominal pain, abdominal bloating, intestinal gas, diarrhea, constipation, nausea, stomach pain, heartburn, and indigestion. Binge drinking was defined as 4+ alcohol-containing drinks/day. RESULTS: Patterns of alcohol intake did not differ between IBS patients and controls. Although patterns of drinking were associated with GI symptoms among women with IBS, this was not the case with the healthy controls. The strongest associations for IBS patients were between binge drinking and the next day's GI symptoms (e.g., diarrhea, P=0.006; nausea, P=0.01; stomach pain, P=0.009; and indigestion, P=0.004), whereas moderate and light drinking either were not associated or weakly associated with GI symptoms. Associations between alcohol intake and GI symptoms were stronger for women with IBS-diarrhea than for IBS-constipation or IBS-mixed. Effects of binge drinking on GI symptoms were strongest when comparing between individuals (rather than within individuals). CONCLUSIONS: Our findings indicate that IBS symptoms differ according to the pattern of alcohol intake among IBS patients, suggesting that the pattern of drinking may in part explain the inconsistent findings between alcohol and IBS symptoms.

Urinary proteome analysis of irritable bowel syndrome (IBS) symptom subgroups.

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by chronic abdominal pain associated with alterations in bowel function. Given the heterogeneity of the symptoms, multiple pathophysiologic factors are suspected to play a role. We classified women with IBS into four subgroups based on distinct symptom profiles. In-depth shotgun proteomic analysis was carried out to profile the urinary proteomes to identify possible proteins associated with these subgroups. First void urine samples with urine creatinine level≥100 mg/dL were used after excluding samples that tested positive for blood. Urine from 10 subjects representing each symptom subgroup was pooled for proteomic analysis. The urine proteome was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a data-independent method known as Precursor Acquisition Independent From Ion Count (PAcIFIC) that allowed extended detectable dynamic range. Differences in protein quantities were determined by peptide spectral counting followed by validation of select proteins with ELISA or a targeted single reaction monitoring (LC-SRM/MS) approach. Four IBS symptom subgroups were selected: (1) Constipation, (2) Diarrhea+Low Pain, (3) Diarrhea+High Pain, and (4) High Pain+High Psychological Distress. A fifth group consisted of Healthy Control subjects. From comparisons of quantitative spectral counting data among the symptom subgroups and controls, a total of 18 proteins that showed quantitative differences in relative abundance and possible physiological relevance to IBS were selected for further investigation. Three of the 18 proteins were chosen for validation by either ELISA or SRM. An elevated expression of gelsolin (GSN) was associated with the high pain groups. Trefoil Factor 3 (TFF3) levels were higher in IBS groups compared to controls. In this study, the IBS patients subclassified by predominant symptoms showed differences in urine proteome levels. Proteins showing distinctive changes are involved in homeostasis of intestinal function and inflammatory response. These findings warrant future studies with larger, independent cohorts to enable more extensive assessment and validation of urinary protein markers as a diagnostic tool in adults with IBS.

Comprehensive self-management reduces the negative impact of irritable bowel syndrome symptoms on sexual functioning.

BACKGROUND: Women with irritable bowel syndrome (IBS) report sexual dysfunction. Comprehensive self-management (CSM) intervention has been shown to reduce gastrointestinal, psychological, and somatic symptoms in IBS women. Whether this intervention also reduces sexual dysfunction is not known. AIMS: We sought to compare demographic and clinical factors in IBS women with and without sexual dysfunction as defined by the Arizona sexual experiences scale (ASEX) and to test the effects of CSM treatment on sexual dysfunction scores and on the sexual relations subscale of an IBS quality of life (IBSQOL) scale which measures the effect of IBS on sexual QOL. METHODS: IBS (Rome II) women enrolled in a randomized clinical trial of CSM treatment were characterized as having sexual dysfunction (N = 89) or not (N = 86) at baseline based on ASEX criteria. Baseline characteristics and symptoms were compared between the two groups. Post-intervention changes were compared between the CSM and the usual care arms of the randomized trial. RESULTS: Women meeting ASEX criteria for sexual dysfunction were older, had higher lifetime depression and antidepressant use, more primary care/MD visits, fewer mental healthcare visits, and greater sleep disturbance than those without sexual dysfunction. No significant group differences in gastrointestinal or somatic symptoms were observed. Compared with usual care treatment, CSM increased sexual QOL scores and had a weaker effect on ASEX scores. CONCLUSIONS: Severity of IBS symptoms at baseline did not differ between IBS women with or without sexual dysfunction. The CSM intervention can reduce the effect of IBS on sexual QOL.

Subtypes of irritable bowel syndrome based on abdominal pain/discomfort severity and bowel pattern.

INTRODUCTION: Irritable bowel syndrome (IBS) has traditionally been classified by stooling pattern (e.g., diarrhea-predominant). However, other patterns of symptoms have long been recognized, e.g., pain severity. Our objective was to examine the utility of subtyping women with IBS based on pain/discomfort severity as well as predominant bowel pattern. METHODS: Women (n = 166) with IBS completed interviews, questionnaires, and kept a diary for 28 days. Rome II questionnaire items eliciting the past year recall of hard and loose stools, and frequency and severity of abdominal pain or discomfort were used to classify participants into six subtypes-three bowel pattern categories by two pain/discomfort severity categories. Concordance of these subtypes with corresponding diary items was examined. Analysis of variance (ANOVA) tested the relationship of bowel pattern and pain categories to measures of quality of life and symptoms. RESULTS: There is moderate congruence of the retrospective classification of bowel pattern and pain/discomfort severity subtypes with prospectively reported stool frequency and consistency and pain severity. Quality of life, impact of IBS on work and daily activities, and cognitive beliefs about IBS differed significantly based on abdominal pain/discomfort category but not on predominant bowel pattern. There is evidence of an interaction, with the effect of pain severity being strong in the IBS-diarrhea and IBS-mixed groups, but this was absent in the IBS-constipation group. Similar results hold for most diary symptoms, except for those directly related to bowel pattern. CONCLUSIONS: Overall, the distress of IBS is more strongly related to the severity of abdominal pain/discomfort than is the predominant stool pattern in patients with IBS. Categorizing IBS patients by abdominal pain/discomfort severity in conjunction with predominant bowel pattern may be useful to clinicians and researchers in developing more effective management.

Genetics and gastrointestinal symptoms.

Gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, constipation, abdominal discomfort/pain, and heartburn are ubiquitous and as such are often the focus of nursing interventions. The etiologies of these symptoms include GI pathology (e.g., cancer, inflammation), dietary factors (e.g., lactose intolerance), infection, stress, autonomic nervous system dysregulation, medications, as well as a host of diseases outside the GI tract. This review focuses on a common condition (irritable bowel syndrome [IBS]) that is linked with both bowel pattern and abdominal discomfort/pain symptoms. Family and twin studies give evidence for a role of genetic factors in IBS. Whether genes are directly associated with IBS or influence disease risk indirectly by modulating the response to environmental factors remains unknown at this time. Given the multifactorial nature of IBS, it is unlikely that a single genetic factor is responsible for IBS. In addition, gene-gene (epistatic) interactions are also likely to play a role. Four genes coding for proteins involved in neurotransmission (i.e., the serotonin reuptake transporter [SERT], tryptophan hydroxylase [TPH], alpha2-adrenergic receptor [alpha2-ADR], catechol-o-methyl transferase [COMT]) and their potential relevance to GI symptoms and IBS will be reviewed. Further research using genome-wide association approaches with samples well characterized by ethnicity and standardized symptom subgrouping is needed.

Does a self-management program change dietary intake in adults with irritable bowel syndrome?

Making dietary changes such as increasing fiber intake is recommended for the management of irritable bowel syndrome symptoms. Few studies have explored the efficacy of education on compliance with recommendations such as increasing fiber, vegetable, and fruit intake in adults with irritable bowel syndrome. This study examined the effect of a multicomponent self-management intervention that included strategies to enhance fiber, vegetable, and fruit intake. Participants with medically diagnosed irritable bowel syndrome were randomized to usual care or individualized comprehensive self-management, delivered either in-person or by telephone. Since previously published analyses show the two delivery modes to be equally effective, the two intervention groups were combined. Of the 188 individuals randomized, 173 participants (113 in the self-management group and 60 in the usual care group; 23 men, 150 women) provided data on at least one of the three follow-up occasions (3, 6, and 12 months postrandomization). Fiber, vegetable, and fruit intakes were measured using the Food Frequency Questionnaire. Participants in the intervention group demonstrated increases (p < .05) in fiber and fruit intake and a trend in vegetable intake at 6 and 12 months postintervention. Improvement in dietary fiber intake following a self-management intervention for IBS continues to 1 year.

A Comprehensive Self-Management Program With Diet Education Does Not Alter Microbiome Characteristics in Women With Irritable Bowel Syndrome.

BACKGROUND AND PURPOSE: Changes in diet and lifestyle factors are frequently recommended for persons with irritable bowel syndrome (IBS). It is unknown whether these recommendations alter the gut microbiome and/or whether baseline microbiome predicts improvement in symptoms and quality of life following treatment. Therefore, the purpose of this study was to explore if baseline gut microbiome composition predicted response to a Comprehensive Self-Management (CSM) intervention and if the intervention resulted in a different gut microbiome composition compared to usual care. METHODS: Individuals aged 18-70 years with IBS symptoms ≥6 months were recruited using convenience sampling. Individuals were excluded if medication use or comorbidities would influence symptoms or microbiome. Participants completed a baseline assessment and were randomized into the eight-session CSM intervention which included dietary education and cognitive behavioral therapy versus usual care. Questionnaires included demographics, quality of life, and symptom diaries. Fecal samples were collected at baseline and 3-month post-randomization for 16S rRNA-based microbiome analysis. RESULTS: Within the CSM intervention group (n = 30), Shannon diversity, richness, and beta diversity measures at baseline did not predict benefit from the CSM intervention at 3 months, as measured by change in abdominal pain and quality of life. Based on both alpha and beta diversity, the change from baseline to follow-up microbiome bacterial taxa did not differ between CSM (n = 25) and usual care (n = 25). CONCLUSIONS AND INFERENCES: Baseline microbiome does not predict symptom improvement with CSM intervention. We do not find evidence that the CSM intervention influences gut microbiome diversity or composition over the course of 3 months.

Comprehensive self-management for irritable bowel syndrome: randomized trial of in-person vs. combined in-person and telephone sessions.

OBJECTIVES: Psychological and behavioral therapies are being increasingly used for symptom management in patients with irritable bowel syndrome (IBS). The aims of this study were to compare two delivery modes for a comprehensive self-management (CSM) intervention, primarily by telephone vs. entirely in person, and to compare each with usual care (UC). METHODS: Adults with IBS were recruited through community advertisement. Subjects (N=188) were randomly assigned to three groups: one in which all nine weekly CSM sessions were delivered in person, one in which six of the nine sessions were conducted over telephone, and one in which subjects received UC. Primary outcome measures were a gastrointestinal (GI) symptom score based on six symptoms from a daily diary and disease-specific quality of life (QOL). These and other outcomes were assessed at baseline and at 3, 6, and 12 months after randomization. Mixed model analyses tested for differences between the three groups in each outcome variable at the three follow-up occasions, controlling for the baseline level of each outcome. RESULTS: Both GI symptom score and QOL showed significantly greater improvement in the two CSM groups than in the UC group (P<0.001), with the magnitude of this difference being quite similar for the three follow-up time points. The two CSM groups experienced a very similar degree of improvement, and there were no statistically significant differences between the two. CONCLUSIONS: A CSM program is efficacious whether delivered primarily by telephone or totally in person, and there is no evidence that replacing six of the in-person sessions by telephone sessions reduces the efficacy of the intervention.

Gender differences in gastrointestinal, psychological, and somatic symptoms in irritable bowel syndrome.

In the United States, more women than men seek health-care services for symptoms of irritable bowel syndrome (IBS). A number of explanations are given for this gender difference including the higher rates of somatic non-gastrointestinal symptoms and increased psychological distress reported by women with IBS. However, these gender differences are found in studies that rely on retrospective recall with little attention to age or reproductive status. The purpose of the current analysis was to prospectively compare the frequency (days/month of moderate to severe based on a daily diary) of somatic, gastrointestinal (GI), and psychological distress symptoms, in menstruating women (N = 89) and postmenopausal women (N = 66) to men (N = 32) with IBS. In addition, the correlation between daily symptoms and daily report of overall health was evaluated. Postmenopausal women reported significantly more GI pain/discomfort symptoms, especially bloating and abdominal distension, than men, however these differences are greatly attenuated when age is controlled for. Both postmenopausal and menstruating women reported significantly more somatic symptoms (especially joint pain and muscle pain) than men with IBS. The effect was stronger in postmenopausal women, whose somatic symptoms were also higher than menstruating women (P = 0.014). Fatigue and stress were higher in women than men but anxiety and depression were not. All three types of symptoms were strongly correlated with self-rating of health, both across and within-person. Gender-related differences in GI and somatic symptoms are apparent in persons with IBS, more strongly in postmenopausal women. The presence of somatic symptoms in postmenopausal women with IBS may challenge clinicians to find suitable therapeutic options.

The serotonin transporter polymorphism rs25531 is associated with irritable bowel syndrome.

Irritable bowel syndrome is a frequent gastrointestinal disorder of unknown etiology. The serotonin transporter regulates the intensity and duration of serotonin signaling in the gut and is, therefore, an attractive candidate gene for irritable bowel syndrome. Previous studies investigating the 5-HTTLPR and Stin2 VNTR polymorphisms of the serotonin transporter have proved inconclusive. In this exploratory study we therefore expanded the search for a possible association of the serotonin transporter with irritable bowel syndrome to include not only the 5-HTTLPR and Stin2 VNTR length polymorphisms, but also the functional single nucleotide polymorphism rs25531. We genotyped 186 patients with irritable bowel syndrome and 50 healthy control subjects raging in age from 18 to 70 years. Carriers of the rare G allele of rs25531 had approximately threefold increased odds of irritable bowel syndrome compared with healthy controls (OR 3.3, 95% CI 1.1-9.6). Our findings suggest that further investigation of the possible role of the serotonin transporter in the etiology of IBS is warranted.

Association of Fatigue With TPH2 Genetic Polymorphisms in Women With Irritable Bowel Syndrome.

Fatigue is the most common extraintestinal symptom in women with irritable bowel syndrome (IBS). Genetic polymorphisms of monoamines are associated with fatigue in many chronic diseases. In this pilot exploratory study, the primary aim was to determine whether genetic polymorphisms of tryptophan hydroxylase ( TPH1/TPH2), serotonin reuptake transporter ( SERT), or catechol-O-methyltransferase ( COMT) are associated with fatigue in women with IBS. Additionally, analysis explored whether these genetic associations with fatigue would be present when controlling for abdominal pain, psychological distress, feeling stressed, and sleepiness during the day. Secondary analysis of two randomized controlled trial baseline data sets in Caucasian women with IBS ( N = 185) was conducted. Participants kept a daily diary with one dimension (i.e., severity) for each of the 26 symptoms, including fatigue, for 28 days prior to randomization. DNA samples were tested for single-nucleotide polymorphisms (SNPs) of TPH1 (four SNPs) /TPH2 (one SNP), SERT (one SNP), and COMT (one SNP). Analysis of covariance was used to examine associations of percentage of diary days with moderate to very severe symptoms with genetic polymorphisms. Only one SNP, TPH2 rs4570625, was significantly associated with fatigue ( p = .005). T-allele (low functional) carriers of TPH2 (i.e., G/T or T/T genotypes) reported a greater percentage of days with moderate to very severe fatigue than G/G homozygotes ( p = .001). Reduced synthesis of tryptophan in the central nervous system may contribute to reports of fatigue in women with IBS. Understanding genetic risk factors for fatigue may elucidate preemptive strategies to reduce fatigue in individuals with IBS.

Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome.

OBJECTIVES: To determine gastrointestinal (GI) permeability and fecal calprotectin concentration in children 7 to 10 years of age with functional abdominal pain and irritable bowel syndrome (FAP/IBS) versus control subjects and ascertain potential relationships with pain symptoms and stooling. STUDY DESIGN: GI permeability and fecal calprotectin concentration were measured. Children kept a 2-week diary of pain episodes and stooling pattern. RESULTS: Proximal GI permeability was greater in the FAP/IBS group (n = 93) compared with control subjects (n = 52) (0.59 +/- 0.50 vs 0.36 +/- 0.26, respectively; mean +/- SD; P < .001) as was colonic permeability (1.01 +/- 0.67 vs 0.81 +/- 0.43, respectively; P < .05). Gastric and small intestinal permeability were similar. Fecal calprotectin concentration was greater in children with FAP/IBS compared with control children (65.5 +/- 75.4 microg/g stool vs 43.2 +/- 39.4, respectively; P < .01). Fecal calprotectin concentration correlated with pain interference with activities (P = .01, r(2) = 0.36). There was no correlation between GI permeability and pain related symptoms. Neither permeability nor fecal calprotectin correlated with stool form. CONCLUSIONS: Children with FAP/IBS have evidence of increased GI permeability and low-grade GI inflammation, with the latter relating to the degree to which pain interferes with activities.