Age Differences in Core Symptoms and Symptom Relationships in Patients With Irritable Bowel Syndrome: A Network Analysis.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age. METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify the core symptoms driving the symptom structure between young (≤45 years) vs older (>45 years) adults with IBS. We evaluated 3 network properties between the 2 age groups: network structure, edge (connection) strength, and global strength. RESULTS: In both age groups, fatigue was the top core symptom. Anxiety was a second core symptom in the younger age group, but not the older age group. Intestinal gas and/or bloating symptoms also exerted considerable influences in both age groups. The overall symptom structure and connectivity were found to be similar regardless of age. DISCUSSION: Network analysis suggests fatigue is a critical target for symptom management in adults with IBS, regardless of age. Comorbid anxiety is likely an important treatment focus for young adults with IBS. Rome V criteria update could consider the importance of intestinal gas and bloating symptoms. Additional replication with larger diverse IBS cohorts is warranted to verify our results.

Cyclic Vomiting Syndrome and Cannabis Hyperemesis Syndrome: The State of the Science.

This article provides a narrative review of the state of the science for both cyclic vomiting syndrome and cannabis hyperemesis syndrome along with a discussion of the relationship between these 2 conditions. The scope of this review includes the historical context of these conditions as well as the prevalence, diagnostic criteria, pathogenesis, and treatment strategies for both conditions. A synopsis of the endocannabinoid system provides a basis for the hypothesis that a lack of cannabidiol in modern high-potency Δ 9 -tetrahydrocannabinol cannabis may be contributory to cannabis hyperemesis syndrome and possibly other cannabis use disorders. In concluding assessment, though the publications addressing both adult cyclic vomiting syndrome and cannabis hyperemesis syndrome are steadily increasing overall, the state of the science supporting the treatments, prognosis, etiology, and confounding factors (including cannabis use) is of moderate quality. Much of the literature portrays these conditions separately and as such sometimes fails to account for the confounding of adult cyclic vomiting syndrome with cannabis hyperemesis syndrome. The diagnostic and therapeutic approaches are, at present, based generally on case series publications and expert opinion, with a very limited number of randomized controlled trials and a complete absence of Level 1 evidence within the cyclic vomiting literature overall as well as for cannabis hyperemesis syndrome specifically.

Exploration of associations among dietary tryptophan, microbiome composition and function, and symptom severity in irritable bowel syndrome.

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS. METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and quantitative measurement of TRP by mass spectrometry. RESULTS: Our cohort included 115 females, 69 with IBS and 46 HCs, with a mean age of 28.5 years (SD 7.4). TRP intake (p = 0.71) and stool TRP level (p = 0.27) did not differ between IBS and HC. Bifidobacterium abundance was lower in the IBS group than in HCs (p = 0.004). Predicted TRP metabolism gene content was higher in IBS than HCs (FDR-corrected q = 0.006), whereas predicted biosynthesis gene content was lower (q = 0.045). Within the IBS group, there was no association between symptom severity and TRP intake or stool TRP, but there was a significant interaction between Bifidobacterium abundance and TRP intake (q = 0.029) in predicting stool character. CONCLUSIONS: Dietary TRP intake, microbiome composition, and differences in TRP metabolism constitute a complex interplay of factors that could modulate IBS symptom severity.

Exploring the Role of Vitamin D and the Gut Microbiome: A Cross-Sectional Study of Individuals with Irritable Bowel Syndrome and Healthy Controls.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and HC (n=62). Plasma concentrations of 25(OH)D were assessed using the Endocrine Society Guidelines definition of vitamin D deficiency (25(OH)D <20 ng/ml) and insufficiency (25(OH)D >20-<30 ng/ml). 16S rRNA microbiome gene sequencing data was available for 39 HC and 62 participants with IBS. Genus-level Bifidobacterium and Lactobacillus and phylum-level Firmicutes and Bacteroidetes relative abundances were extracted from microbiome profiles. Results showed vitamin D deficiency in 40.3% (n=25) vs. 41.4% (n=41), and insufficiency 33.9% (n=21) vs. 34.3% (n=34) in the HCs vs. IBS groups, respectively. The odds of IBS did not differ depending on 25(OH)D status (p=0.75 for deficient, p=0.78 for insufficient), and the average plasma vitamin D concentration did not differ between IBS (mean 24.8 ng/ml) and HCs (mean 25.1 ng/ml; p=0.57). We did not find evidence of an association between plasma 25(OH)D concentration and richness, Shannon index, Simpson index or specific bacterial abundances in either HCs or the IBS group.

Symptom management needs of patients with irritable bowel syndrome and concurrent anxiety and/or depression: A qualitative study.

AIMS: To understand the experiences and needs of symptom management among individuals with irritable bowel syndrome and concurrent symptoms of anxiety and/or depression. DESIGN: This study used a qualitative descriptive research design. METHODS: Individuals with a diagnosis of irritable bowel syndrome and concurrent symptoms of anxiety and/or depression participated were recruited through an online ResearchMatch and a listserv. Semi-structured interviews focused on symptoms and experiences with symptom management interventions conducted from June to August 2020. Interviews were transcribed and data were analysed based on thematic analysis. RESULTS: Twelve individuals participated in this study; all reported current irritable bowel syndrome and anxiety/depression symptoms. The data analysis cumulated with three themes related to symptom management: (a) irritable bowel syndrome negatively impacts physical and mental well-being; (b) a trial and error approach to symptom management; and (c) challenges with healthcare professionals supporting symptom management including negative interactions with healthcare professionals and lack of nutritional expertize and support. CONCLUSION: There is a need for individualized approaches which consider patients' current symptoms of anxiety and depression, previous experiences with the trial-and-error process and consideration for intervention delivery methods. IMPACT: There is a limited qualitative research focusing on the experiences of individuals with irritable bowel syndrome and concurrent symptoms of anxiety and/or depression. This research highlights the need for individualized approaches to enhance symptom management that acknowledges patients' psychological state and past negative experiences with providers and prior dietary regimens.

Hypnosis and relaxation interventions for chronic pain management in cancer survivors: a randomized controlled trial.

PURPOSE: Nonpharmacological interventions such as hypnosis show promising evidence for the self-management of pain and pain-related sequelae among cancer survivors. The purpose of this study was to evaluate the efficacy of a 4-week recorded hypnosis intervention in reducing pain intensity compared to a recorded relaxation intervention in cancer survivors with chronic pain. METHODS: Adult cancer survivors were randomly assigned to listen to hypnosis (n = 55) or relaxation recordings (n = 54) daily for 28 days. Primary (pain intensity) and secondary outcomes (pain interference, anxiety, depression, fatigue, sleep disturbance) measures were completed pre- and post-treatment. Treatment effects were evaluated using a series of analyses of covariance. RESULTS: Both hypnosis and relaxation provided significant and moderate to large improvements in the primary outcome and the secondary outcomes of pain interference and anxiety (ds = 0.44-0.88). The hypnosis group also experienced a moderate improvement in fatigue (d = 0.47) and sleep disturbance (d = 0.54). The effect size for pain reduction from pre- to post-treatment for the hypnosis group was d = 0.86 and for the relaxation group, d = 0.88. There were no significant between-group differences in primary and secondary outcomes from pre- to post-treatment. CONCLUSIONS: The results support that recorded hypnosis and relaxation interventions are similarly effective in reducing pain and the pain-related sequelae of pain interference and anxiety among cancer survivors with chronic pain. The hypnosis intervention also reduced fatigue and sleep disturbance. Audio recordings can provide a convenient delivery method of nonpharmacological interventions to self-manage chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03867760, registered March 8, 2019.

Risk Factors for Abdominal Pain-Related Disorders of Gut-Brain Interaction in Adults and Children: A Systematic Review.

BACKGROUND & AIMS: Many studies have assessed risk factors of irritable bowel syndrome (IBS) and other abdominal pain-related disorders of gut-brain interaction (AP-DGBI); however, the role of these factors is unclear due to heterogeneous study designs. The aim of this systematic review was to extensively evaluate the literature and determine clinical risk and protective factors for the presence and persistence of AP-DGBI in children and adults. METHODS: A PubMed search identified studies investigating potential risk and protective factors for AP-DGBI in adults and children. Inclusion criteria included fully published studies with a control group; exclusion criteria included poor-quality studies (using a validated scale). For each factor, the proportion of studies that found the factor to be a risk factor, protective factor, or neither was summarized. The number of studies, diagnostic criteria, number of subjects, and average study quality rating provided further context. Whenever possible, a meta-analysis generated pooled odds ratios or mean difference. RESULTS: The systematic review included 348 studies. Female sex, gastroenteritis, abuse, stress, psychological disorders, somatic symptoms, and poor sleep were consistent risk factors for developing AP-DGBI in adults and children. In adults, additional risk factors included obesity, smoking, and increased use of medical resources. Protective AP-DGBI factors in adults included social support and optimism; no studies for protective factors were found for children. CONCLUSIONS: There are multiple risk factors for AP-DGBI in adults and children. These include female sex, gastroenteritis, abuse, stress, poor sleep, obesity, psychological disorders, and somatic symptoms. Additional studies are needed in children, on protective factors, and on factors associated with persistence of AP-DGBI.

Delivery Methods of Cognitive Behavior Therapy for Patients With Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is the most commonly diagnosed gastrointestinal disorder and negatively impacts individuals' quality of life. Cognitive behavioral therapy appears effective for reducing symptoms in many irritable bowel syndrome patients. However, the optimal methods to deliver cognitive behavioral therapy and the effective treatment dosage for patients with IBS remain unclear. This article aims to provide an update on cognitive behavioral therapy research in IBS, particularly considering the dose of treatment, route of delivery (in-person vs. web- and telephone-based delivery), and outcome measures. A systematic literature review was conducted using databases of PubMed, CINAHL Complete, and Web of Science from 2008 through 2021. Twelve studies reporting randomized clinical trials comparing cognitive behavioral therapy delivered with in-person, telephone, and web for the management of IBS symptoms among adults with irritable bowel syndrome were found. The dose of treatment varied from 4 to 10 sessions. Six different scales measured various outcomes. No severe adverse reactions to cognitive behavioral therapy were reported. Cognitive behavioral therapy is an effective treatment for IBS symptoms regardless of the dose and the route of treatment. However, it is difficult to compare the effectiveness of these randomized clinical trials due to the various cognitive behavioral therapy protocols, combined routes of therapy delivery, and different outcome measures used.

Impact of COVID-19 on Individuals With Irritable Bowel Syndrome and Comorbid Anxiety and/or Depression.

GOALS: The goal of this study was to describe the influence of the COVID-19 pandemic on ability to engage in activities and the influence on psychological distress and gastrointestinal symptoms among individuals with irritable bowel syndrome (IBS) and comorbid anxiety and/or depression. BACKGROUND: Individuals with IBS and comorbid anxiety and/or depression report increased symptoms and decreased quality of life compared with individuals with IBS alone. The current COVID-19 pandemic has the potential to further influence symptoms among individuals with IBS and comorbid anxiety and/or depression. STUDY: Individuals who met the Rome-IV IBS criteria and reported mild to severe anxiety and/or depression were included. Participants completed an online survey with questions about anxiety, depression, impact of COVID on activities and symptoms, and demographics. RESULTS: Fifty-five individuals participated in the study. The COVID-19 pandemic most commonly influenced their ability to spend time with friends and family, shop for certain types of food, and access health care. Participants also reported increased stress (92%), anxiety (81%), and depressive symptoms (67%). Finally, around half the sample reported increases in abdominal pain (48%), diarrhea (45%), or constipation (44%). CONCLUSIONS: The COVID-19 pandemic is related to self-reported increases in psychological distress and gastrointestinal symptoms among individuals with IBS and comorbid anxiety and/or depression. Additional research is needed to intervene on these symptoms.

Early Evidence Indicates Vitamin D Improves Symptoms of Irritable Bowel Syndrome: Nursing Implications and Future Research Opportunities.

Irritable bowel syndrome (IBS) affects approximately 11.2% of the population. Yet, full understanding of its etiology and optimal treatment remains elusive. Understanding of the underlying pathophysiology of IBS has been limited. However, research is beginning to identify the cause as multifactorial (e.g., low-grade local mucosal inflammation, systemic immune activation, altered intestinal permeability, intestinal hypersensitivity, altered central nervous system processing, changes in intestinal microbiota). Understanding of the role of vitamin D in intestinal inflammation, immunity, and gastrointestinal conditions is increasing but is not yet fully understood. Growing evidence has linked vitamin D deficiency with a variety of gastrointestinal disorders, including inflammatory bowel disease, diverticulitis, colorectal cancer, and IBS. Several studies have demonstrated that individuals with IBS are more likely to have vitamin D deficiency than healthy controls. Recent vitamin D supplementation studies have shown improvement in quality of life and reduction in IBS symptoms (including abdominal pain, distention, flatulence, constipation, and visceral sensitivity) but the mechanism remains unclear. Nurses are well positioned to educate patients about the importance of sufficient vitamin D for overall health in individuals with IBS as well as participate in well-designed therapeutic studies to explore whether enhanced vitamin D status will ultimately help treat IBS more effectively.

Irritable bowel syndrome in midlife women: a narrative review.

Midlife women between the ages of 40 and 65 years have reported multiple challenges due to menopausal, developmental, and situational transitions from younger to older adulthood. During the midlife period, many women seek health care for gastrointestinal symptoms and irritable bowel syndrome (IBS). Multiple factors including stress, poor sleep, diet, and physical inactivity may contribute to IBS or gastrointestinal symptoms in midlife women. As such, a comprehensive assessment and treatment approach is needed for midlife women suffering gastrointestinal symptoms. This article reviews the main aspects of the menopausal transition, sex hormonal changes, abdominal and pelvic surgery, psychosocial distress, behavioral factors, and gut microbiome, as well as their relevance on IBS and gastrointestinal symptoms in midlife women. Also, management strategies for IBS in midlife women are discussed. To date, gastrointestinal symptoms during midlife years remain a critical area of women's health. Additional research is needed to better understand the contributors to gastrointestinal symptoms in this group. Such efforts may provide a new window to refine or develop treatments of gastrointestinal symptoms for midlife women.

Associations between chronotype, social jetlag, and weekday sleep in women with irritable bowel syndrome.

Sleep deficiency is well-documented in individuals with irritable bowel syndrome (IBS). Sleep deficiency includes poor sleep quality and an inadequate amount of sleep, and is a modifiable risk factor for IBS symptom exacerbations. Prior studies in other populations have identified chronotype and social jetlag (SJL) as important determinants of sleep outcomes. However, chronotype and SJL have not been examined in women with IBS. We used multiple linear regression analyses to determine whether chronotype and SJL are associated with sleep outcomes during weekdays among women with IBS predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), and healthy control (HC) women. This sample included 62 women with IBS (IBS-C = 29, IBS-D = 33) and 58 HC women who completed a 28-day daily diary from two study cohorts. The average age of the participants was 30.1 (SD 7.2) years. Chronotype was estimated from daily diary data with the average mid-sleep time on weekends (MSWwe). SJL was calculated by subtracting the average mid-sleep time on weekdays from MSWwe. Sleep outcomes included diary assessments of sleep quality, sleep need met, and restorative sleep during weekdays. In HCs, later chronotype was predictive of lower sleep quality (ß = -0.19, p < .01), a perception of sleep need not met (ß = -0.17, p < .001), and a less restorative sleep during weekdays (ß = -0.15, p = .073), whereas SJL was not associated with sleep outcomes. Similar to HCs, earlier chronotypes in women with IBS-C reported better sleep quality and more sufficient sleep need met and restorative sleep during weekdays than later chronotypes (all p > .05). Compared to HCs, the relationships of chronotype with weekday sleep outcomes in the women with IBS-D were in the opposite directions (all p < .05). This exploratory study suggests that chronotype expression may reflect the temporal associations of sleep outcomes within IBS bowel pattern predominance subgroups, particularly sleep quality and sleep need met. Additional investigations are warranted to examine whether specific temporal attributes of symptoms and/or symptom severity associated with IBS subgroups contribute to chronotype expression.

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.

Bile Acids and Microbiome Among Individuals With Irritable Bowel Syndrome and Healthy Volunteers.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. High bile acid (BA) profiles have been associated with abdominal pain symptoms, mucosal inflammation, and diarrhea in a subgroup of those with IBS. The purpose of this study was to compare: 1) fecal primary and secondary BAs in women with and without IBS; and 2) symptoms, gut microbiome, and diet between women with high and normal BAs (i.e., similar to healthy [HC] women). Women (ages 18-45) with IBS and HCs were recruited from healthcare providers or the community. Participants kept a 28-day symptom diary, completed a 3-day food journal, and collected a stool sample for microbiome analysis (16 S rRNA gene sequencing). Primary and secondary BA levels were determined by mass spectrometry. Primary BAs did not differ between IBS (n = 45) and HC (n = 28) groups; women with IBS had significantly increased conjugated secondary BAs (glycodeoxycholic acid [p = 0.006], taurodeoxycholic acid [p = 0.006], and glycolithocholic acid [p = 0.01]). Sixty percent of women with IBS had normal BAs whereas 40% had high BAs. Women with high fecal BAs were predominantly IBS-Diarrhea or IBS-Mixed and consumed less fiber and vegetable protein and more animal protein compared to women with IBS whose fecal BAs levels were comparable to HCs. Those with high conjugated secondary fecal BAs also had a greater Firmicutes/Bacteroidetes ratio, less abundance of phylum Bacteroidetes and genus Gemmiger, and more abundance of family Erysipelotrichaceae compared to IBS women with normal BAs. Determination of fecal BA levels provides additional insights into pathophysiological links between diet and microbiome in IBS.

Sex Hormones, BDNF, Leptin, and TGF-ß1 in Females With IBS: A Pilot Investigation.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition predominantly affecting the female sex, and is characterized by brain-gut axis dysregulation. Relevance of hormones along the hypothalamic-pituitary gonadal axis and hypothalamic-pituitary adrenal axis to IBS symptomatology remain unclear, as does the significance of other modulators including brain derived neurotrophic factor (BDNF), leptin, and transforming growth factor ßeta 1 (TGF-ß1). METHODS: Females with IBS were compared with female healthy controls (HC) on age, race, hormonal contraceptive use, body mass index, adrenocorticotropic hormone, cortisol, estradiol, follicular stimulating hormone, luteinizing hormone, progesterone, total cholesterol, Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS). BDNF, leptin, and TGF-ß1 were quantified using enzyme-linked immunosorbent assay. Descriptive statistics, non-parametric techniques, and regression analyses were performed. RESULTS: Participants with IBS (n = 12) displayed higher estradiol (p = .027) than did HC (n = 21). Direction of associations among study variables often differed between groups: BDNF and progesterone in HC (rs = .623) and in IBS (rs = -.723). The relationship between log (CES-D) and log (estradiol) varied by IBS status (interaction term p = 0.019). DISCUSSION: Elevated estradiol in participants with IBS, and differential patterns of biological and psychological indices between groups, encourages further inquiry on the relevance of sex hormones, BDNF, leptin, and TGF-ß1 to symptoms of IBS. Future research endeavors should conduct longitudinal quantification of sex hormones with subjective symptom assessment to facilitate insight on the pathophysiology and female sex bias in IBS.

Probiotic VSL#3 Treatment Reduces Colonic Permeability and Abdominal Pain Symptoms in Patients With Irritable Bowel Syndrome.

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function. Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment. Results: Fifteen subjects completed the trial (4-week: n = 8; 8-week: n = 7). Number of pain episodes decreased in both groups (P = 0.049 and P = 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances of Streptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum, and Lactobacillus casei subsp. paraccasei correlated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment. Conclusions: Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial. Clinical Trial Registration: www.clinicaltrials.gov, Identifier: NCT00971711.

Cytokine Levels and Symptoms Among Women with Irritable Bowel Syndrome: Considering the Role of Hormonal Contraceptive Use.

BACKGROUND: Young to middle-aged women are more likely than men to be diagnosed with irritable bowel syndrome (IBS). Immune dysfunction may be present in IBS, however, few studies have tested whether hormonal contraceptive use is linked to inflammatory markers. The purpose of this study was to compare cytokine levels between women (ages 18-45) with and without IBS and with and without hormonal contraceptive use and to examine the relationships of cytokine levels to IBS gastrointestinal (GI) and non-GI symptoms within those using and not using hormonal contraceptives. METHODS: Seventy-three women with IBS and 47 healthy control women completed questionnaires (demographics, hormonal contraceptive use) and kept a 28-day symptom diary. Fasting plasma and LPS-stimulated pro-inflammatory (IL-1ß, IL-6, IL-12p40, IL-12p70, IL-8, and TNF-α) and anti-inflammatory (IL-10) cytokines were assayed. RESULTS: No differences were found in plasma or stimulated cytokine levels between IBS and control women. Levels of IL-1ß (p = 0.04) and TNF-α (p = 0.02) were higher among women who did not use hormonal contraceptives compared to women who used hormonal contraceptives. Among women with IBS, significant correlations were found between daily psychological distress and plasma IL-10, IL-12p70, IL-1ß, IL-6, and IL-8 cytokine levels. CONCLUSIONS: These results suggest that hormonal contraceptive use might reduce IL-1ß and TNF-α cytokine levels in women with IBS. The impact of hormonal contraceptive use on innate immune activation among women with IBS requires further research.

Indirect effect of sleep on abdominal pain through daytime dysfunction in adults with irritable bowel syndrome.

STUDY OBJECTIVES: Sleep deficiency, psychological distress, daytime dysfunction, and abdominal pain are common in adults with irritable bowel syndrome. Prior research on individuals with chronic pain has identified the indirect effect of sleep on pain through psychological distress or daytime dysfunction; however, this effect is less clear in irritable bowel syndrome. The purpose of this study was to examine potential indirect effects of sleep on abdominal pain symptoms simultaneously through psychological distress and daytime dysfunction in adults with irritable bowel syndrome. METHODS: Daily symptoms of nighttime sleep complaints (sleep quality and refreshment), psychological distress, daytime dysfunction (fatigue, sleepiness, and difficulty concentrating), and abdominal pain were collected in baseline assessments from 2 randomized controlled trials of 332 adults (mean age 42 years and 85% female) with irritable bowel syndrome. Structural equation modeling was used to examine the global relationships among nighttime sleep complaints, psychological distress, daytime dysfunction, and abdominal pain. RESULTS: The structural equation modeling analyses found a strong indirect effect of poor sleep on abdominal pain via daytime dysfunction but not psychological distress. More than 95% of the total effect of nighttime sleep complaints on abdominal pain was indirect. CONCLUSIONS: These findings suggest that the primary impact of nighttime sleep complaints on abdominal pain is indirect. The indirect effect appears primarily through daytime dysfunction. Such understanding provides a potential avenue to optimize personalized and hybrid behavioral interventions for adults with irritable bowel syndrome through addressing daytime dysfunction and sleep behaviors. Additional study integrating symptoms with biological markers is warranted to explore the underlying mechanisms accounting for these symptoms. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov. Name: Nursing Management of Irritable Bowel Syndrome: Improving Outcomes, Nursing Management of IBS: Improving Outcomes. URLs: https://clinicaltrials.gov/ct2/show/NCT00167635, https://clinicaltrials.gov/ct2/show/NCT00907790. Identifiers: NCT00167635, NCT00907790.

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.