Altered Structural Covariance of Insula, Cerebellum and Prefrontal Cortex Is Associated with Somatic Symptom Levels in Irritable Bowel Syndrome (IBS).
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ABSTRACT:
SUBMITTER: Grinsvall C
PROVIDER: S-EPMC8699158 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC3631108 | biostudies-literature
Project description:ObjectiveSome IBS patients possess detailed memories of the events surrounding their bowel symptom onset ("episodic memories"). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories.MethodsReferral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories.Results14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories.ConclusionsIBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology.
| S-EPMC9243497 | biostudies-literature
Project description:Abnormal gut-brain interactions are common in irritable bowel syndrome (IBS), but the associations between neurophysiological measures and their relation to gastrointestinal (GI) symptoms are poorly understood. Our aim was to explore these relationships and define the most relevant neurophysiology measures for GI symptom severity in IBS. IBS patients underwent small intestinal motility (manometry; fasted and fed contraction frequency, phase III time) and secretion (transmural potential difference), rectal sensorimotor (barostat; sensory thresholds, tone response, compliance), autonomic nervous system (baroreceptor sensitivity and effectiveness), and colonic motor function (transit time) examinations. GI symptom severity (GSRS-IBS), and anxiety and depression (HAD) as a proxy measure of central nervous system (CNS) dysfunction, were assessed. In total 281 IBS patients (Rome II criteria) were included (74% females, median age 36 [interquartile range 28-50] years). Significant correlations between neurophysiology measures were stronger within, rather than between, different neurophysiological examinations. The strongest neurophysiology-symptom correlations occurred between a combination of CNS and visceral sensitivity parameters, and GSRS-IBS total score and pain domain (ρ = 0.40, p < 0.001, and ρ = 0.38, p < 0.001). Associations between GI symptoms in IBS and individual and combinations of neurophysiological factors occurred, primarily in CNS and visceral sensitivity measures, providing new insights into the clinical presentation of IBS.
| S-EPMC7300023 | biostudies-literature
Project description:BackgroundManagement of diarrhoea-predominant irritable bowel syndrome (IBS-D) is generally based on patient-reported symptoms; however, limited information on symptom severity exists. The objective of the study was to assess the impact of IBS-D severity on patient burden and patient and healthcare professional attitudes towards IBS.MethodsWe conducted two web-based surveys of healthcare professionals and patients from Australia, Canada and Europe. We analysed patient characteristics and attitudes by IBS-D severity, which was assessed retrospectively using a composite of four variables: worst abdominal pain, IBS symptom frequency, Bristol Stool Form Scale and quality of life.ResultsOf 679 healthcare professional respondents, one-third routinely classified patients by severity. The patient survey was completed by 513 patients with mild (26%), moderate (33%) and severe (41%) IBS-D, classified using the composite scale. Age, sex and treatment satisfaction did not change with severity; however, 19% of patients classified with severe IBS-D agreed with the statement: 'When my IBS is bad, I wish I was dead' versus 4 and 7% of patients with mild and moderate IBS-D, respectively (p < 0.05). Significantly more patients classified with severe IBS-D reported medication use versus mild IBS-D.ConclusionCompared with milder symptoms, severe IBS-D was associated with increased medication use and a negative perspective of IBS-D. This highlights the need for a validated severity scale to inform treatment decisions.
| S-EPMC7183708 | biostudies-literature
Project description:BackgroundIrritable bowel syndrome (IBS) is a brain-gut disorder, of which the natural course varies between patients and is difficult to predict. This study aimed to evaluate symptom evolution over a 5-year follow-up period and to identify baseline predictors for symptom severity and quality of life (QoL) at follow-up.MethodsMaastricht IBS cohort participants completed questionnaires upon inclusion regarding demographics and lifestyle, gastrointestinal (GI) symptoms, anxiety and depression, and QoL. The same questionnaires, in addition to others, were completed after 5 years. Rome criteria were confirmed face-to-face at initial enrollment and through telephonic interviews at follow-up.Key resultsAt a mean follow-up of 4.7 years, 379 patients were approached of whom 203 (53.7%) responded. Of these, 161 were reached by telephone and analyzed; 49 (30.4%) did not fulfill the Rome III criteria at follow-up and had lower levels of GI symptoms and GI-specific anxiety compared to those remaining Rome III-positive (P < 0.001). However, Rome III-negative patients had comparable levels of QoL and life satisfaction, comorbid anxiety and depression, work absenteeism, and impaired productivity. No baseline predictors were found for being Rome III-positive or Rome III-negative. However, greater age and lower baseline physical QoL predicted lower physical QoL at follow-up (P < 0.005 and P < 0.01, respectively), while lower baseline mental QoL predicted lower mental QoL at follow-up (P = 0.005). Additionally, higher anxiety and depression scores at follow-up were associated with lower QoL and life satisfaction at follow-up (P < 0.001).Conclusions and inferencesLong-term QoL and general well-being might depend on concurrent psychological symptoms, rather than GI symptom improvement.
| S-EPMC6852246 | biostudies-literature
Project description:BackgroundAlthough irritable bowel syndrome (IBS) is more common in women, little is known about the role of hormonal changes and menopause in IBS. This study aimed to evaluate for differences in gastrointestinal (GI) and psychological symptoms between pre- and postmenopausal women with IBS compared to age-matched men with IBS.MethodsPatients with Rome-positive IBS were identified. Premenopausal women were <45 years of age with regular menses. Postmenopausal women were ≥45 years without menses for at least 1 year. Younger men were <45 years, and older men were ≥45 years. Questionnaires measured severity of IBS symptoms, somatic symptoms, health-related quality of life (HRQOL), and psychological symptoms. Multivariable linear or logistic regressions evaluating relationships between age and sex were performed.Key results190 premenopausal women (mean age 30.25 years), 52 postmenopausal women (mean age 54.38 years), 190 men <45 years (mean age 30.45 years), and 52 men ≥45 years (mean age 53.37 years) were included. Postmenopausal IBS women had greater severity of IBS symptoms (P = .003) and worse physical HRQOL (P = .048) compared to premenopausal women. No differences were observed between age-matched older and younger IBS men. Constipation increased with age for both sexes but was the principal IBS subtype in women only.Conclusions and inferencesPostmenopausal women with IBS have more severe IBS symptoms than premenopausal women, while no comparable age-related changes were seen in IBS men. The modulatory effect of female sex hormones on brain-gut interactions which affect visceral perception and GI function likely contributes to these findings.
| S-EPMC7529855 | biostudies-literature
Project description:BackgroundDiarrhea-predominant irritable bowel syndrome (IBS-d) significantly diminishes the health-related quality of life (HRQOL) of patients. Psychological and social impacts are common with many IBS-d patients reporting comorbid depression, anxiety, decreased intimacy, and lost working days. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire is a 34-item instrument developed and validated for measurement of HRQOL in non-subtyped IBS patients. The current paper assesses this previously-validated instrument employing data collected from 754 patients who participated in a randomized clinical trial of a novel treatment, eluxadoline, for IBS-d.MethodsPsychometric methods common to HRQOL research were employed to evaluate the IBS-QOL. Many of the historical analyses of the IBS-QOL validations were used. Other techniques that extended the original methods were applied where more appropriate for the current dataset. In IBS-d patients, we analyzed the items and substructure of the IBS-QOL via item reduction, factor structure, internal consistency, reproducibility, construct validity, and ability to detect change.ResultsThis study supports the IBS-QOL as a psychometrically valid measure. Factor analyses suggested that IBS-specific QOL as measured by the IBS-QOL is a unidimensional construct. Construct validity was further buttressed by significant correlations between IBS-QOL total scores and related measures of IBS-d severity including the historically-relevant Irritable Bowel Syndrome Adequate Relief (IBS-AR) item and the FDA's Clinical Responder definition. The IBS-QOL also showed a significant ability to detect change as evidenced by analysis of treatment effects. A minority of the items, unrelated to the IBS-d, performed less well by the standards set by the original authors.ConclusionsWe established that the IBS-QOL total score is a psychometrically valid measure of HRQOL in IBS-d patients enrolled in this study. Our analyses suggest that the IBS-QOL items demonstrate very good construct validity and ability to detect changes due to treatment effects. Furthermore, our analyses suggest that the IBS-QOL items measure a univariate construct and we believe further modeling of the IBS-QOL from an item response theory (IRT) approach under both non-treatment and treatment conditions would greatly further our understanding as item-based methods could be used to develop a short form.
| S-EPMC3895767 | biostudies-literature
Project description:Background: Irritable Bowel Syndrome (IBS) is a widespread disease with variable symptoms that have an important impact on the quality of life. Despite the prevalence of IBS, its etiology and pathophysiology are still to be fully understood, but immune response is known to be involved. In this study, we investigated the variation of two specific cytokines, B-cell activating factor (BAFF) and platelet-activating factor (PAF), the levels of food-specific IgG and the symptom severity, using Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS), following a personalized and unrestricted-calorie diet.Methods: We enrolled 30 subjects with diagnosis of IBS, according to Rome-IV criteria, whose inflammatory markers were measured at baseline and after 6 weeks of dietary intervention. The subjects were monitored in a general practice outpatient setting and nutritional advice was offered remotely via two telephone sessions with a nutritionist.Results: BAFF and PAF values did not differ between baseline and end of study, both in compliant (C) and non-compliant (NC) subjects. IgG levels significantly decreased only in compliant subjects: 37.32 (23.24-93.67) IU/mL; 27.9 (7.56-93.96) IU/mL (p?=?0.02) and in non-compliant went from 51.83 (13.17-113.1) IU/mL to 44.06 (4.96-255.4) IU/mL (p?=?0.97, ns). IBS-SSS significantly decreased in both compliant subjects, from 245 (110-480) to 110 (0-140) (p?<?0.0001), and non compliant subjects, from 250 (155-370) to 100 (7-220) (p?<?0.0001). Comparing IBS-SSS between week 3 and week 6, only compliant subjects had a significant reduction, from 155 (50-355) to 110 (0-140) (p?=?0.005), versus non-compliant, from 115 (35-315) to 100 (7-220) (p?=?0.33, ns).Conclusion: These findings support the rapid efficacy and suitability of a personalized dietetic intervention with outside consultation in IBS.Trial registration: ClinicalTrials.gov ID NCT04348760 Registered April 15, 2020 (retrospectively registered) https://clinicaltrials.gov/show/NCT04348760.
| S-EPMC7708901 | biostudies-literature
Project description:BACKGROUND:Inflammatory mechanisms of ulcerative colitis (UC) and irritable bowel syndrome (IBS) may overlap or are part of different spectrums. However, potential links between inflammation and IBS-like symptoms in these patient groups are still unclear. The aim of this study was to determine if the systemic inflammatory protein (SIP) profiles differ between UC patients, with presence of inflammation or in remission with or without IBS-like symptoms, and IBS patients. METHODS:Serum from patients with active UC (UCA), UC patients in remission with or without IBS-like symptoms (UCR?+?IBS, UCR-IBS), IBS patients (IBS), and healthy subjects (HS) was analyzed using the ProSeek Multiplex Inflammation kit, which detects 92 proteins. RESULTS:The exploratory cohort consisted of 166 subjects (UCA, n = 40; UCR-IBS, n = 45; UCR?+?IBS, n = 20; IBS, n = 40; HS, n = 21). Systemic inflammatory protein profiles separated UC from non-UC (HS and IBS) patients in multivariate analysis, revealing caspase 8, axin 1, sulfotransferase 1A1, and tumor necrosis factor superfamily member 14 as the variables most important to clustering. Although minor differences were detected between UCR?+?IBS and UCR-IBS, SIP profiles discriminated UCA from UCR, and interleukin (IL) 17C, IL17A, chemokine ligand 9, and transforming growth factor-? characterized active inflammation. SIP profiles weakly discriminated HS from IBS, although fibroblast growth factor 21 and IL6 serum levels were higher in IBS. Results were confirmed in a validation cohort (UCA, n = 15; UCR?+?IBS, n = 9; IBS, n = 14). CONCLUSIONS:SIP profiles distinguish UC patients from IBS patients, irrespective of inflammation or IBS-like symptoms, suggesting that inflammatory mechanisms of the diseases are part of different spectrums.
| S-EPMC7216771 | biostudies-literature
Project description:BACKGROUND & AIMS:Irritable bowel syndrome (IBS) is a stress-sensitive disorder associated with dysregulation of the hypothalamic-pituitary-adrenal axis. We studied the cumulative effect of events during adulthood on this pathway in patients with IBS. METHODS:We studied 129 patients with IBS, based on Rome III criteria (mean age 28.1 years, 66% women), and 108 healthy individuals (controls; mean age 29.8 years, 60% women) who completed the Life Experiences Survey from August 2013 to September 2017. Data were collected on the presence and effects of events since age 18, IBS severity scores, and IBS-related quality of life. For a subset of subjects, we measured serum cortisol and adrenocorticotropic hormone (ACTH) production in response to administration of corticotropin-releasing factor and ACTH. RESULTS:Compared with controls, patients with IBS perceived more adulthood life events as negative and had a significantly higher negative life event impact score (14.17 ± 12.04 vs 10.83 ± 9.98; P=.022). In patients with IBS, the presence of more-negatively perceived adulthood life events was associated with worse IBS symptom severity (? = 1.53, 95% CI, 0.21-2.84; P = .025) and IBS-related quality of life (? = -0.70; 95% CI, -1.02 to -0.38; P < .001). Negatively perceived adulthood life events were associated with reduced production of ACTH in response to corticotropin-releasing factor in patients with IBS compared with controls (P < .05). CONCLUSION:In a study of more than 200 subjects, we associated more-negatively perceived events during adulthood with an increased risk for IBS, worse symptom severity and quality of life, and a dysregulated stress response. Understanding the effects of events that cause stress in adults and their perceived effects on IBS may help guide disease management.
| S-EPMC6609507 | biostudies-literature