The effect of mindfulness interventions on stress in medical students: A systematic review and meta-analysis.

BACKGROUND: Medical students have high levels of stress, which is associated with higher incidents of burnout, depression, and suicide compared to age-matched peers. Mindfulness practices have been shown to reduce stress among medical students. PURPOSE: The purpose of this systematic review and meta-analysis was to examine if mindfulness interventions have an overall effect on stress outcomes in the high-stress population of medical students globally, particularly given the wide variety of interventions. Any intervention designed to promote mindfulness was included. METHODS: A comprehensive literature search was completed to include multiple databases, ancestry, and hand-searching and 35 studies were included. Standardized mean difference effect sizes (ES) were synthesized across studies using a random-effects model for changes in stress levels in medical students ≥ 18. Moderator analyses were performed to explore variations in effects by participant and intervention characteristics. RESULTS: Mindfulness interventions significantly improved stress among medical students in both the two-arm studies (d = 0.370, k = 19, n = 2,199, 95% CI 0.239-0.501, p < .001) and one-arm pre-post studies (d = 0.291, k = 30, n = 18 (two cohorts from Dyrbye et al), 95% CI 0.127-0.455, p = 0.001). Moderator analyses found trends in less hours and less required practice resulted in better improvement in stress. CONCLUSIONS: This study further confirms that despite a wide variety of mindfulness interventions for medical students around the world, they produce an overall small-to-moderate effect on stress reduction. Future research looking at the most effective protocols for high-stress medical students would be beneficial.

Prevalence, characteristics and measurement of somatic symptoms related to mental health in medical students: a scoping review.

INTRODUCTION: Somatic symptoms related to mental health in medical students are under-researched, with nothing on the topic being published in the United States in over three decades. This scoping review is the first of its kind to explore the prevalence, type and severity of somatic symptoms induced by stress, anxiety, depression and burnout amongst medical students, with the objective of describing the significance and breadth of this issue. METHODS: PRISMA-ScR guidelines were used to guide this review. A comprehensive search was performed of 22 databases, followed by bibliographic and hand searching. Inclusion criteria were published, peer-reviewed articles with a sample of medical students and at least one measure of somatic symptoms related to mental health, in English or with an English-language translation. Excluded were review, companion and editorial articles. Coding was done by an experienced coder trained in systematic review techniques. Two authors reviewed each article. RESULTS: Twenty-nine articles met inclusion criteria, representing 16 countries, 31 schools/teaching hospitals and 9,887 medical students. The prevalence of somatic symptoms ranged from 5.7 to 80.1%, and somatic symptoms were overwhelmingly found to be significantly correlated with mental ill-health. Somatic symptoms included back pain, neck pain, headaches, sleep disturbances and functional gastrointestinal disorders. Eleven different outcome measures were used, with varying degrees of validity and reliability, which were compared and assessed. CONCLUSIONS: Somatic symptoms appear strongly correlated with mental ill-health in medical students, and are likely highly prevalent. This review highlights the need for further research on somatic symptoms of mental ill-health in medical students, particularly in the United States, and the addition of larger, multi-institutional cohorts to expand our understanding of prevalence, incidence and inciting factors of somatic symptoms. Longitudinal studies tracking somatic symptoms' effect on career trajectory and professional burnout levels are also needed. Finally, future research should explore interventions for reducing physical symptom burden in medical students.

This scoping review is the first of its kind to explore the breadth and depth of knowledge on the presence, prevalence, type and severity of somatic symptoms related to stress experienced by medical students across the globe, and if or how physical symptoms of stress have been addressed thus far.Medical students are known to have chronically high levels of stress, but somatic symptoms of stress are not well researched in this population, particularly in the United States, where no research has been done on this topic in over three decades.This scoping review finds that across many different countries, medical students consistently report high rates of physical symptoms, including musculoskeletal pain and gastrointestinal disorders, which are highly correlated with stress and other mental health conditions.This review provides the first initial assessment of the outcome measures used for somatic symptoms related to mental health.Further research on the impact of physical symptoms in medical students, and how this might relate to medical students' mental health and eventual career burnout, is warranted.

Remote Usability Testing to Facilitate the Continuation of Research.

Usability testing has historically been an in-person activity where test participants and evaluation researchers are co-located. Recruiting participants into usability studies can be a challenging endeavor especially when potential participants are concerned about time commitments and social distancing. The global COVID-19 pandemic has driven the development of remote usability testing methods. In this paper, we describe remote usability testing as it evolved during a pre-pandemic research study. We adapted our in-person usability evaluation methodology for a commercially available mHealth app to a remote usability testing methodology to accommodate potential participants during a more convenient participant-identified time. In doing so we met the needs, preferences, and availability of our participants and maintained research progress. Adapting to patient-centered needs through remote usability testing has the potential to facilitate continued research and engage potential participants due to its convenience, flexibility, and decrease constraints presented by geographic limits.

Digital Methodology for Mobile Clinical Decision Support Development in Long-Term Care.

The global COVID-19 pandemic has driven innovations in methods to sustain initiatives for the design, development, evaluation, and implementation of clinical support technology in long-term care settings while removing risk of infection for residents, family members, health care workers, researchers and technical professionals. We adapted traditional design and evaluation methodology for a mobile clinical decision support app - designated Mobile Application Information System for Integrated Evidence ("MAISIE") - to a completely digital design methodology that removes in-person contacts between the research team, developer, and nursing home staff and residents. We have successfully maintained project continuity for MAISIE app development with only minor challenges while working remotely. This digital design methodology can be implemented in projects where software can be installed without in-person technical support and remote work is feasible. Team skills, experience, and relationships are key considerations for adapting to digital environments and maintaining project momentum.

Usability Evaluation of a Smartphone Medication Reminder Application in Patients Treated With Short-term Antibiotic.

Medication adherence is poor in persons with chronic disease, especially in those with multiple chronic diseases, one of which is a psychological disorder. Social support, medication education, and external reminders have been identified as facilitators of adherence. Mobile health applications have the potential to enhance adherence; however, it is unknown if publicly available applications are user-friendly and useful. We aimed to examine the usability and feasibility of the "MediSafe" medication reminder application in adults with diarrhea-predominant irritable bowel syndrome undergoing short-term antibiotic therapy and a "Medfriend" from their social support network (N = 14). A mixed-methods study was conducted. All patient participants used the MediSafe application daily for 14 days. Ease of use, ease of learning, and satisfaction scales were rated highest by both patient participants and Medfriends, whereas usefulness was rated lowest by both groups, with Medfriends' usefulness rating significantly lower than that of patient participants. Telephone interviews identified patient participants found the application instrumental in facilitating medication adherence, and Medfriends viewed themselves as active participants in the patient participants' care. The MediSafe medication reminder application is easy to use and accepted by both patients and their designated Medfriend. The MediSafe is instrumental in facilitating short-term antibiotic adherence and social support engagement.

Patient Perspectives on Short-Course Pharmacotherapy: Barriers and Facilitators to Medication Adherence.

BACKGROUND: Medication nonadherence is a public health issue that contributes to poor health outcomes and health-care costs. Factors influencing long-term medication adherence are known; however, little is known about short-course medication adherence. OBJECTIVE: This study examined patient perspectives on adherence and factors that influence adherence to short-course pharmacotherapy in diarrhea-predominant irritable bowel syndrome. METHOD: Twenty-seven participants were interviewed to identify their perceptions of barriers and facilitators to thrice-daily, 14-day rifaximin. RESULTS: Participants were primarily female (89%), aged 18 to 65 years. Sixty-eight percent of interviewees were identified as "low-adherers," meaning the percentage of days with correct daily dosing of rifaximin was <80%. The final coding framework identified social/economic-related (family support and medication expense), system-related (relationship with provider and medication knowledge), condition-related (symptom severity), therapy-related (inconvenient dosing), and patient-related (forgetfulness and busyness of daily life) factors that influenced adherence. CONCLUSION: The resulting patient perspectives highlight a diverse set of factors that influence short-course adherence and the need for tailored interventions that address these various factors resulting in enhanced patient outcomes.

Adherence to Short-course Pharmacotherapy in Adults with Irritable Bowel Syndrome.

Irritable Bowel Syndrome (IBS), characterized by abdominal pain and bowel dysfunction, treatment focuses on alleviating symptoms. Adherence is crucial for pharmacologic management success. We examined 73 adult's objective adherence to rifaximin using the taxonomy for adherence. Demographic, quality of life (QOL), psychological distress, perceived stress, adverse childhood experiences (ACE), pain, and adherence data were collected. Impaired QOL, elevated psychological distress and perceived stress, and a significant number of ACE were reported at baseline. Average time to prescription initiation was 2.5 days. Once implemented, 92% missed midday dose and persisted 5 days beyond the prescribed dose. High-adherers reported lower pain levels post-rifaximin compared to low-adherers. Objective adherence was significantly lower than self-reported. Objective adherence was not predicted by above variables. Adherence to rifaximin is poor in those with IBS. Future research examining perceived barriers/facilitators toward rifaximin adherence may provide insight into patient-centered, modifiable targets for adherence interventions and improve patient-related outcomes.

Effects of a comprehensive self-management intervention on extraintestinal symptoms among patients with IBS.

OBJECTIVE: Adults with irritable bowel syndrome (IBS) often report extraintestinal pain, fatigue, and sleep disturbances in addition to abdominal pain. Few interventions have sought to reduce these extraintestinal symptoms within the IBS population. To address this, we compared the effects of a comprehensive self-management (CSM) intervention to a control intervention (usual care) on extraintestinal pain, fatigue, and sleep disturbances among patients with IBS. METHOD: Data were obtained from 243 IBS patients participating in two CSM intervention trials. Daily symptom diaries were collected at baseline, 3 and 6 months post-randomization. Daily symptoms of headache, backache, muscle pain, joint pain, fatigue, sleepiness during the day, sleep quality, and refreshed by sleep were analyzed. Analysis of covariance was used to determine the effects of the intervention on each symptom at 3 and 6 months controlling for 'study' and baseline symptom levels. RESULTS: Patients in the CSM intervention group reported decreased symptoms of fatigue, sleep disturbances, backache and headache compared to usual care at 3 and 6 months. The CSM group also reported significantly decreased joint pain at 3 months compared to usual care, but not 6 months. No significant difference was found for muscle pain. CONCLUSIONS: An existing CSM intervention is effective in reducing fatigue and sleep disturbances. However, mixed results for extraintestinal pain indicates a need to better differentiate between underlying mechanisms. Addressing such symptoms is important to decrease the overall burden of IBS, reduce health care expenditures, and improve patients' quality of life. TRIAL REGISTRATION: NCT00907790; NCT00167635.

Colon Epithelial MicroRNA Network in Fatty Liver.

Background & Aims: Intestinal barrier alterations are associated with fatty liver (FL) and metabolic syndrome (MetS), but microRNA (miR) signaling pathways in MetS-FL pathogenesis remain unclear. This study investigates an epithelial-focused miR network in colorectal cell models based on the previously reported MetS-FL miR trio of hsa-miR-142-3p, hsa-miR-18b, and hsa-miR-890. Methods: Each miR mimic construct of MetS-FL miR trio was transfected into human colorectal cells, CRL-1790 or Caco-2. Global miRNome changes posttransfection were profiled (nCounter® Human v3 miRNA, NanoString Technologies). Changes in barrier (transepithelial electrical resistance, TEER) and epithelial cell junction structure (Occludin and Zona Occludens-1/ZO-1 immunofluorescence staining-confocal microscopy) were examined pre- and posttransfection in Caco-2 cell monolayers. A signaling network was constructed from the MetS-FL miR trio, MetS-FL miR-induced colorectal miRNome changes, ZO-1, and Occludin. Results: Transfection of CRL-1790 cells with each MetS-FL miR mimic led to global changes in the cellular miRNome profile, with 288 miRs being altered in expression by more than twofold. Eleven miRs with known cytoskeletal and metabolic roles were commonly altered in expression by all three miR mimics. Transfection of Caco-2 cell monolayers with each MetS-FL miR mimic induced barrier-associated TEER variations and led to structural modifications of ZO-1 and Occludin within epithelial cell junctions. Pathway analysis incorporating the MetS-FL miR trio, eleven common target miRs, ZO-1, and Occludin revealed a signaling network centered on TNF and AKT2, which highlights injury, inflammation, and hyperplasia. Conclusions: Colon-specific changes in epithelial barriers, cell junction structure, and a miRNome signaling network are described from functional studies of a MetS-FL miR trio signature.

Layperson's knowledge and perceptions of irritable bowel syndrome as potential barriers to care.

AIMS: The aim of this study was to describe the layperson's knowledge and perceptions regarding the aetiology, pathogenesis, prevalence, medical evaluation, diagnosis and treatment of irritable bowel syndrome. BACKGROUND: Diagnosis acceptance and adherence to treatment is influenced by the views of the patient's social networks. Little is known how these networks influence those with irritable bowel syndrome. DESIGN: Cross-sectional study of two-hundred four laypersons, ages 18-80 years without an irritable bowel syndrome diagnosis. METHODS: Data were collected May 2016-March 2017. Laypersons without a diagnosis of IBS self-reported their knowledge and perceptions about IBS. RESULTS/FINDINGS: Participants were able to identify many symptoms associated with irritable bowel syndrome however held misconceptions regarding the development of irritable bowel syndrome as noted by the endorsement of genetics, environment and diet or alcohol/smoking behaviours as specific causes. Further misconceptions held included the belief that irritable bowel syndrome was associated with an increased risk for the development of colon cancer and inflammatory bowel disease. Contrary to current guidelines, many thought a gastroenterologist was the only person appropriate to diagnose irritable bowel syndrome and objective testing, such as colonoscopy, was necessary to establish a diagnosis. CONCLUSION: Laypersons have an understanding of the symptoms associated with IBS; however, hold numerous misconceptions regarding the aetiology, role of the healthcare provider, necessary testing and risks associated with irritable bowel syndrome. These misconceptions are inconsistent with current guidelines and practices. Establishing partnerships and educating social networks in addition to patients may enhance outcomes for those with IBS.

Gender and Weight Influence Quality of Life in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and bowel dysfunction in the absence of structural abnormality. Diagnosis can be challenging and often leads to extensive medical tests, non-effective therapeutic modalities, and reduced quality of life (QOL). Identifying factors associated with dysfunction have the potential to enhance outcomes. Participants with IBS (n = 41) and healthy volunteers (n = 74) were recruited into this cross-sectional, descriptive, natural history protocol at the National Institute of Health, Clinical Center. Demographic characteristics were self-reported. QOL was assessed with the Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire. Statistical analysis included descriptive statistics, factorial ANOVA, and multiple regression. Individuals with IBS reported lower QOL scores across all QOL-subscales compared to healthy controls. Normal-weight women and overweight men with IBS reported the greatest QOL impairment. Body fat percent had confounding effects on the relationship between IBS and QOL. The disparity between QOL scores in participants with IBS by both gender and weight groups may reflect different social pressures perceived by normal and overweight women and men. These findings enhance the recognition of the disparities in patients with chronic symptoms and thereby lead to personalized assessment and interventions to improve their QOL.

The association of catastrophizing with quality-of-life outcomes in patients with irritable bowel syndrome.

BACKGROUND: Catastrophizing is a cognitive process characterized by a propensity to concentrate on and magnify the value of an actual or anticipated painful stimulus and negatively assesses one's ability to cope. Catastrophizing is an important predictor of pain-related outcomes. A cornerstone symptom of irritable bowel syndrome (IBS) is abdominal pain or discomfort. Also individuals with IBS have been reported to have a tendency to catastrophize. In a sample of individuals who suffer from IBS, we hypothesized that those individuals who catastrophize (catastrophizers) would have worse outcomes as compared to those who do not catastrophize (non-catastrophizers). METHODS: One hundred and one adults with IBS (79% female, mean age 42 years, 97% Caucasian) were recruited from outpatient clinics and data were collected through self-report measures. Catastrophizing was measured with the catastrophizing subscale of the Coping Strategies Questionnaire, illness representations were measured with The Revised Illness Perception Questionnaire (IPQ-R), psychological distress was measured with the Brief Symptom Inventory 18 (BSI-18), and health-related quality of life was measured using the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) measure. Descriptive statistics, correlations, and multiple linear regression analyses were completed to describe participants, the associations of the variables of interest, and the unique relationship between psychosocial variables and HRQOL. RESULTS: Overall, participants reported poor HRQOL (M = 63.32, range 0-100). Catastrophizers differed significantly on IBS-QOL from non-catastrophizers (M = 48.98 vs. non-catastrophizers M = 78.53; p < 0.001), BSI-18 (M = 21.35 vs. non-catastrophizers M = 6.76; p < 0.001), and IPQ-R, specifically the consequences (M = 21.75 vs. non-catastrophizers M = 17.20; p < 0.001) and emotional representations (M = 20.90 vs. non-catastrophizers M = 15.43; p < 0.001). Catastrophizing was positively correlated with the consequences (r = .54; p < 0.01) and emotional representations (r = .65; p < 0.01) and negatively correlated with total HRQOL (r = -0.76; p < 0.01). CONCLUSION: The findings indicated that participants who catastrophized reported worse psychosocial and functional outcomes. Thus, catastrophizing, in addition to psychological distress variables, may be an important factor to address in optimizing health outcomes in individuals with IBS. In addition, illness perceptions were strongly related to catastrophizing and HRQOL; assessment and integration of illness perceptions as well as catastrophizing into the management of individuals who suffer with IBS may maximize the health outcomes.

Data supporting the effects of lysozyme on mRNA and protein expression in a colonic epithelial scratch wound model.

Colonic epithelial health is implicated in a host of gastrointestinal (GI) diseases and disorders. Lysozyme is suspected to play a role in the ability of the epithelium to recover from injury (Abey et al., in press; Gallo, 2012; Rubio, 2014) [1], [2], [3]. Disrupted repair mechanisms may lead to delayed or ineffective recovery and disruptions to epithelial biology resulting in GI symptoms and altered barrier function (Peterson and Artis, 2014) [4]. The effect of lysozyme on the transcriptomic and proteomic profile of healthy colonic epithelial cells was investigated. Epithelial cells in culture were scratch wounded and treated with lysozyme. mRNA and protein profiles were simultaneously quantified in the same sample using a digital counting technology. Gene and protein expressions altered by the presence or absence of lysozyme are described in this article. Extensive statistical and bioinformatic analysis, and interpretation of the results can be found in "Lysozyme association with circulating RNA, extracellular vesicles, and chronic stress" (Abey et al., in press) [1].

Lysozyme association with circulating RNA, extracellular vesicles, and chronic stress.

BACKGROUND: Stress has demonstrated effects on inflammation though underlying cell-cell communication mechanisms remain unclear. We hypothesize that circulating RNAs and extracellular vesicles (EVs) in patients with chronic stress contain signals with functional roles in cell repair. METHODS: Blood transcriptome from patients with Irritable Bowel Syndrome versus controls were compared to identify signaling pathways and effectors. Plasma EVs were isolated (size-exclusion chromatography) and characterized for effectors' presence (immunogold labelling-electron microscopy). Based on transcriptome pathways and EV-labelling, lysozyme's effects on cell migration were tested in human colon epithelial CRL-1790 cells and compared to the effects of CXCL12, a migration inducer (wound assay). The effect of lysozyme on immune-linked mRNA and protein levels in cells which survived following serum starvation and scratch wound were investigated (NanoString). RESULTS: Blood transcriptomes revealed pyridoxal 5'phosphate salvage, pyrimidine ribonucleotides salvage pathways, atherosclerosis, and cell movement signaling with membrane CD9 and extracellular lysozyme as effectors. Plasma EVs showed labelling with CD9, mucins, and lysozyme. This is the first identification of lysozyme on plasma EVs. In CRL-1790 cells, lysozyme induced migration and repaired scratch wound as well as CXCL12. Immune mRNA and protein expressions were altered in cells which survived following serum starvation and scratch wound, with or without lysozyme in serum-free media post-wounding: CD9, IL8, IL6 mRNAs and CD9, NT5E, PD-L1 proteins. CONCLUSIONS: Repair and inflammatory signals are identified in plasma EVs and circulating RNAs in chronic stress. Registered clinicaltrials.gov #NCT00824941. GENERAL SIGNIFICANCE: This study highlights the role of circulating RNAs and EVs in stress.

The Gastrointestinal Pain Pointer: A Valid and Innovative Method to Assess Gastrointestinal Symptoms.

Abdominal pain is a chronic condition experienced by approximately 20% of individuals in the United States. The purpose of the study was to assess the validity of the Gastrointestinal Pain Pointer as a measure of abdominal pain intensity. A prospective longitudinal time-series study design was utilized. The sample included 93 outpatients (58.1% female). Participants met Rome III criteria for irritable bowel syndrome (n = 32) or were healthy controls (n = 61). The Gastrointestinal Pain Pointer, a new electronic pain assessment tool, was used to assess self-reported abdominal pain intensity among participants before and after ingestion of an intestinal permeability test solution across 11 time points over a 5-hour time period. The results were compared with the Short-Form McGill Pain Questionnaire. The Gastrointestinal Pain Pointer was found to be valid in the assessment of abdominal pain intensity. The tool is a novel and valid measure of abdominal pain intensity that enhances the ability for clinicians to better quantify, in real time, patient-related pain outcomes for both clinical care and research.

Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform.

The gene expression platform assay allows for robust and highly reproducible quantification of the expression of up to 800 transcripts (mRNA or miRNAs) in a single reaction. The miRNA assay counts transcripts by directly imaging and digitally counting miRNA molecules that are labeled with color-coded fluorescent barcoded probe sets (a reporter probe and a capture probe). Barcodes are hybridized directly to mature miRNAs that have been elongated by ligating a unique oligonucleotide tag (miRtag) to the 3' end. Reverse transcription and amplification of the transcripts are not required. Reporter probes contain a sequence of six color positions populated using a combination of four fluorescent colors. The four colors over six positions are used to construct a gene-specific color barcode sequence. Post-hybridization processing is automated on a robotic prep station. After hybridization, the excess probes are washed away, and the tripartite structures (capture probe-miRNA-reporter probe) are fixed to a streptavidin-coated slide via the biotin-labeled capture probe. Imaging and barcode counting is done using a digital analyzer. The immobilized barcoded miRNAs are visualized and imaged using a microscope and camera, and the unique barcodes are decoded and counted. Data quality control (QC), normalization, and analysis are facilitated by a custom-designed data processing and analysis software that accompanies the assay software. The assay demonstrates high linearity over a broad range of expression, as well as high sensitivity. Sample and assay preparation does not involve enzymatic reactions, reverse transcription, or amplification; has few steps; and is largely automated, reducing investigator effects and resulting in high consistency and technical reproducibility. Here, we describe the application of this technology to identifying circulating miRNA perturbations in irritable bowel syndrome.

Effect of Illness Representations and Catastrophizing on Quality of Life in Adults With Irritable Bowel Syndrome.

There is limited understanding of the influence of psychosocial factors on irritable bowel syndrome (IBS), which contributes to management difficulties and ineffective long-term treatment. The goal of the current study was to assess the effect illness representations and coping had on health-related quality of life (HRQOL) in adults with IBS. Self-report data were collected from 101 adults with IBS. Illness representations were measured with the Revised Illness Perception Questionnaire; catastrophizing was measured with the catastrophizing subscale of the Coping Strategies Questionnaire; and HRQOL was measured using the IBS-Quality of Life Measure. Participants perceived their IBS to be a chronic, cyclical condition with negative consequences, moderate symptomatology, and strong negative emotional impact. Their quality of life was poor and catastrophic thinking was noted to be used. Therefore, integrating illness beliefs and coping style into the management of IBS may improve well-being and minimize suffering. [Journal of Psychosocial Nursing and Mental Health Services, 54(9), 44-53.].

Neuroimaging the brain-gut axis in patients with irritable bowel syndrome.

AIM: To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome (IBS). METHODS: A database search for relevant literature was conducted using PubMed, Scopus and Embase in February 2015. Date filters were applied from the year 2009 and onward, and studies were limited to those written in the English language and those performed upon human subjects. The initial search yielded 797 articles, out of which 38 were pulled for full text review and 27 were included for study analysis. Investigations were reviewed to determine study design, methodology and results, and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations. RESULTS: Analysis of study data resulted in the abstraction of four key themes: Neurohormonal differences, anatomic measurements of brain structure and connectivity, differences in functional responsiveness of the brain during rectal distention, and confounding/correlating patient factors. Studies in this review noted alterations of glutamate in the left hippocampus (HIPP), commonalities across IBS subjects in terms of brain oscillation patterns, cortical thickness/gray matter volume differences, and neuroanatomical regions with increased activation in patients with IBS: Anterior cingulate cortex, mid cingulate cortex, amygdala, anterior insula, posterior insula and prefrontal cortex. A striking finding among interventions was the substantial influence that patient variables (e.g., sex, psychological and disease related factors) had upon the identification of neuroanatomical differences in structure and connectivity. CONCLUSION: The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.

The microbiome of the oral mucosa in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions. In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity. The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r2 > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of ß-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS.

Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis.

AIM: To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis. METHODS: The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naïve and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array. RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 ± 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naïve rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naïve animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with controls (P = 0.193). CONCLUSION: Alterations in VIP expression may play a role in IBS. Therefore, a better understanding of the physiology of VIP could lead to new therapeutics.