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  1. Article ; Online: Maximizing Training and Mentorship in Sex as a Biological Variable Research Across Different Brain-Body Disorders.

    Chang, Lin / Gupta, Arpana / Naliboff, Bruce D / Labus, Jennifer / Kilpatrick, Lisa A / Mayer, Emeran A

    Journal of women's health (2002)

    2023  Volume 32, Issue 8, Page(s) 869–876

    Abstract: The Specialized Center of Research Excellence (SCORE) on sex differences at University of California, Los Angeles (UCLA) has a long track record studying bidirectional interactions between different organs and the brain in health and disease with a ... ...

    Abstract The Specialized Center of Research Excellence (SCORE) on sex differences at University of California, Los Angeles (UCLA) has a long track record studying bidirectional interactions between different organs and the brain in health and disease with a strong focus on sex as a biological variable (SABV). While the initial focus was on brain-gut interactions in irritable bowel syndrome (IBS), one of the most common disorders of gut-brain interaction, the scope of our Center's research has expanded to a range of different diseases, including inflammatory bowel disease, alcohol use disorder, obesity, urological chronic pelvic pain syndrome, and vulvodynia. This expansion of research focused on the role of brain-body and brain-gut microbiome interactions in these various disorders, aligning well with the increasing importance of multidisciplinary and interdisciplinary team science. The SCORE's Career Enhancement Core (CEC) has modeled team science as applied to SABV research, with educational and training opportunities, a mentoring program, seed grant funding, and other career development experiences that enable mentees to work across the disciplines involved in brain body research. The CEC goals are: (1) To provide seed grant funds for innovative research relevant to the overall SCORE mission and research program; (2) to recruit and foster the career development of students, trainees, and junior investigators who conduct research focused on sex differences or women's health in IBS and chronic constipation and other brain-gut disorders; (3) to facilitate and promote collaboration between the UCLA SCORE and other academic programs involved in women's health education and research; and (4) to promote the importance of SABV through community outreach using collaborative and innovative approaches. These goals focus on establishing the leading research center in sex differences in basic, translational, and clinical aspects of brain-body interactions and on providing women and underrepresented individuals with research opportunities needed to become independent investigators.
    MeSH term(s) Humans ; Female ; Male ; Mentors ; Irritable Bowel Syndrome ; Mentoring ; Women's Health ; Brain
    Language English
    Publishing date 2023-08-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1139774-3
    ISSN 1931-843X ; 1059-7115 ; 1540-9996
    ISSN (online) 1931-843X
    ISSN 1059-7115 ; 1540-9996
    DOI 10.1089/jwh.2022.0504
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    Zs.A 3584: Show issues Location:
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  2. Article ; Online: Neural correlates of perceived and relative resilience in male and female patients with irritable bowel syndrome.

    Kilpatrick, Lisa A / Gupta, Arpana / Tillisch, Kirsten / Labus, Jennifer S / Naliboff, Bruce D / Mayer, Emeran A / Chang, Lin

    Neurogastroenterology and motility

    2023  Volume 36, Issue 2, Page(s) e14710

    Abstract: Background: Patients with irritable bowel syndrome (IBS) show lower resilience than healthy controls (HCs), associated with greater symptom severity and worse quality of life. However, little is known about affected markers of resilience or the ... ...

    Abstract Background: Patients with irritable bowel syndrome (IBS) show lower resilience than healthy controls (HCs), associated with greater symptom severity and worse quality of life. However, little is known about affected markers of resilience or the influence of sex. Furthermore, as resilience is complex, a comprehensive assessment, with multiple resilience measures, is needed. Therefore, we aimed to evaluate perceived and relative resilience and their neural correlates in men and women with IBS.
    Methods: In 402 individuals (232 IBS [73.3% women] and 170 HCs [61.2% women]), perceived resilience was assessed by the Connor-Davidson Resilience Scale (CDRISC) and Brief Resilience Scale (BRS); relative resilience was assessed by the standardized residual of the Short Form-12 mental component summary score predicted by the Adverse Childhood Experiences score. Non-rotated partial least squares analysis of region-to-region resting-state connectivity data was used to define resilience-related signatures in HCs. Disease and sex-related differences within these signatures were investigated.
    Key results: Scores on all resilience measures were lower in IBS than in HCs (p's < 0.05). In all three resilience-related signatures, patients with IBS showed reduced connectivity largely involving the central autonomic network (p's < 0.001). Men with IBS showed lower CDRISC scores than women with IBS, and greater reductions in CDRISC-related connectivity, associated with worse symptom severity (p < 0.05).
    Conclusions and inferences: Individuals with IBS show reduced perceived and relative resilience, with reduced connectivity suggesting impaired homeostasis maintenance. Men with IBS may show additional impairment in specific aspects of resilience. Treatments aimed at improving resilience may benefit patients with IBS, especially men with IBS.
    MeSH term(s) Humans ; Male ; Female ; Irritable Bowel Syndrome ; Resilience, Psychological ; Quality of Life ; Severity of Illness Index ; Psychological Tests
    Language English
    Publishing date 2023-11-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1186328-6
    ISSN 1365-2982 ; 1350-1925
    ISSN (online) 1365-2982
    ISSN 1350-1925
    DOI 10.1111/nmo.14710
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    Zs.A 2979: Show issues Location:
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  3. Article ; Online: Cognitive Behavioral Therapy for Chronic Pelvic Pain: What Is It and Does It Work?

    Lackner, Jeffrey M / Clemens, J Quentin / Radziwon, Christopher / Danforth, Teresa L / Ablove, Tova S / Krasner, Susan S / Vargovich, Alison M / O'Leary, Patricia C / Marotto, Tracy / Naliboff, Bruce D

    The Journal of urology

    2024  Volume 211, Issue 4, Page(s) 539–550

    Abstract: Purpose: Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome in women and men and chronic prostatitis/chronic pelvic pain syndrome in men, is a common, often disabling urological disorder that is ... ...

    Abstract Purpose: Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome in women and men and chronic prostatitis/chronic pelvic pain syndrome in men, is a common, often disabling urological disorder that is neither well understood nor satisfactorily treated with medical treatments. The past 25 years have seen the development and validation of a number of behavioral pain treatments, of which cognitive behavioral therapy (CBT) is arguably the most effective. CBT combines strategies of behavior therapy, which teaches patients more effective ways of behaving, and cognitive therapy, which focuses on correcting faulty thinking patterns. As a skills-based treatment, CBT emphasizes "unlearning" maladaptive behaviors and thoughts, and replacing them with more adaptive ones that support symptom self-management.
    Materials and methods: This review describes the rationale, technical procedures, and empirical basis of CBT.
    Results: While evidence supports CBT for treatment-refractory chronic pain disorders, there is limited understanding of why or how CBT might work, for whom it is most beneficial, or the specific UCPPS symptoms (eg, pain, urinary symptoms) it effectively targets. This is the focus of EPPIC (Easing Pelvic Pain Interventions Clinical Research Program), a landmark NIH trial examining the efficacy of low-intensity, home-based CBT for UCPPS relative to a nonspecific comparator featuring self-care recommendations of AUA guidelines.
    Conclusions: Systematic efforts to increase both the efficiency of CBT and the way it is delivered (eg, home-based treatments) are critical to scaling up CBT, optimizing its therapeutic potential, and reducing the public health burden of UCPPS.
    MeSH term(s) Male ; Humans ; Female ; Chronic Pain/therapy ; Chronic Pain/psychology ; Syndrome ; Cystitis, Interstitial/diagnosis ; Pelvic Pain/diagnosis ; Cognitive Behavioral Therapy
    Language English
    Publishing date 2024-01-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 3176-8
    ISSN 1527-3792 ; 0022-5347
    ISSN (online) 1527-3792
    ISSN 0022-5347
    DOI 10.1097/JU.0000000000003847
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    Zs.MO 331: Show issues

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  4. Article ; Online: Long-Term Symptom Trajectories in Urologic Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.

    Bradley, Catherine S / Gallop, Robert / Sutcliffe, Siobhan / Kreder, Karl J / Lai, H Henry / Clemens, J Quentin / Naliboff, Bruce D

    Urology

    2022  Volume 169, Page(s) 58–64

    Abstract: Objective: To characterize Urologic Chronic Pelvic Pain Syndrome (UCPPS) pain and urinary symptom trajectories with up to 9 years of follow-up and evaluate whether initial 1-year trajectories are associated with longer-term changes.: Materials and ... ...

    Abstract Objective: To characterize Urologic Chronic Pelvic Pain Syndrome (UCPPS) pain and urinary symptom trajectories with up to 9 years of follow-up and evaluate whether initial 1-year trajectories are associated with longer-term changes.
    Materials and methods: Data were analyzed from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network's prospective observational protocols including the Epidemiology and Phenotyping Study (EPS; baseline to Year 1), EPS Extension (EXT; Years 1-5), and Symptom Patterns Study (SPS: 3-year study; Years 3-9). Adults with Interstitial Cystitis/Bladder Pain Syndrome or Chronic Prostatitis/Chronic Pelvic Pain Syndrome provided patient-reported assessments biweekly (EPS), every 4 months (EXT), or quarterly (SPS). Primary outcomes were composite pain (0-28) and urinary (0-25) severity scores. Multi-phase mixed effects models estimated outcomes over time, adjusted for baseline severity and stratified by EPS symptom trajectory.
    Results: 163 participants (52% women; mean ± SD age 46.4 ± 16.1 years) completed EPS and enrolled in EXT; 67 also enrolled in SPS. Median follow-up was 4.6 years (range 1.3-9.0). After 1 year: 27.6%, 44.8% and 27.6% and 27.0%, 38.0% and 35.0% were improved, stable or worse in pain and urinary symptom severity, respectively. On average, pain and urinary symptom scores did not change further during EXT and SPS periods.
    Conclusions: Women and men with UCPPS showed remarkable stability in pain and urinary symptom severity for up to 9 years, irrespective of their initial symptom trajectory, suggesting UCPPS is a chronic condition with stable symptoms over multiple years of follow-up.
    MeSH term(s) Adult ; Male ; Female ; Humans ; Middle Aged ; Pelvic Pain/diagnosis ; Pelvic Pain/epidemiology ; Pelvic Pain/etiology ; Prostatitis/complications ; Prostatitis/diagnosis ; Chronic Pain/etiology ; Chronic Pain/complications ; Cystitis, Interstitial/complications ; Cystitis, Interstitial/diagnosis ; Syndrome ; Genital Diseases, Female
    Language English
    Publishing date 2022-08-09
    Publishing country United States
    Document type Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 192062-5
    ISSN 1527-9995 ; 0090-4295
    ISSN (online) 1527-9995
    ISSN 0090-4295
    DOI 10.1016/j.urology.2022.07.045
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    Zs.A 1142: Show issues Location:
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    Zs.MO 275: Show issues

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  5. Article ; Online: Validation of a simple body map to measure widespread pain in urologic chronic pelvic pain syndrome: A MAPP Research Network study.

    Clemens, J Quentin / Locke, Kenneth / Landis, J Richard / Kreder, Karl / Rodriguez, Larissa V / Yang, Claire C / Tu, Frank F / Harte, Steven E / Schrepf, Andrew / Farrar, John T / Sutcliffe, Siobhan / Naliboff, Bruce D / Williams, David A / Afari, Niloofar / Spitznagle, Theresa / Taple, Bayley J / Lai, H Henry

    Neurourology and urodynamics

    2024  Volume 43, Issue 3, Page(s) 727–737

    Abstract: Purpose: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with ... ...

    Abstract Purpose: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only.
    Materials and methods: A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site.
    Results: Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations.
    Conclusions: These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes.
    MeSH term(s) Humans ; Male ; Female ; Pelvic Pain/diagnosis ; Pelvic Pain/psychology ; Chronic Pain/diagnosis ; Chronic Pain/psychology ; Syndrome ; Pain Threshold ; Pain Measurement ; Cystitis, Interstitial/diagnosis ; Prostatitis
    Language English
    Publishing date 2024-01-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604904-7
    ISSN 1520-6777 ; 0733-2467
    ISSN (online) 1520-6777
    ISSN 0733-2467
    DOI 10.1002/nau.25400
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  6. Article ; Online: Mediation of the association between disadvantaged neighborhoods and cortical microstructure by body mass index.

    Kilpatrick, Lisa A / Zhang, Keying / Dong, Tien S / Gee, Gilbert C / Beltran-Sanchez, Hiram / Wang, May / Labus, Jennifer S / Naliboff, Bruce D / Mayer, Emeran A / Gupta, Arpana

    Communications medicine

    2023  Volume 3, Issue 1, Page(s) 122

    Abstract: Background: Living in a disadvantaged neighborhood is associated with worse health outcomes, including brain health, yet the underlying biological mechanisms are incompletely understood. We investigated the relationship between neighborhood disadvantage ...

    Abstract Background: Living in a disadvantaged neighborhood is associated with worse health outcomes, including brain health, yet the underlying biological mechanisms are incompletely understood. We investigated the relationship between neighborhood disadvantage and cortical microstructure, assessed as the T1-weighted/T2-weighted ratio (T1w/T2w) on magnetic resonance imaging, and the potential mediating roles of body mass index (BMI) and stress, as well as the relationship between trans-fatty acid intake and cortical microstructure.
    Methods: Participants comprised 92 adults (27 men; 65 women) who underwent neuroimaging and provided residential address information. Neighborhood disadvantage was assessed as the 2020 California State area deprivation index (ADI). The T1w/T2w ratio was calculated at four cortical ribbon levels (deep, lower-middle, upper-middle, and superficial). Perceived stress and BMI were assessed as potential mediating factors. Dietary data was collected in 81 participants.
    Results: Here, we show that worse ADI is positively correlated with BMI (r = 0.27, p = .01) and perceived stress (r = 0.22, p = .04); decreased T1w/T2w ratio in middle/deep cortex in supramarginal, temporal, and primary motor regions (p < .001); and increased T1w/T2w ratio in superficial cortex in medial prefrontal and cingulate regions (p < .001). Increased BMI partially mediates the relationship between worse ADI and observed T1w/T2w ratio increases (p = .02). Further, trans-fatty acid intake (high in fried fast foods and obesogenic) is correlated with these T1w/T2w ratio increases (p = .03).
    Conclusions: Obesogenic aspects of neighborhood disadvantage, including poor dietary quality, may disrupt information processing flexibility in regions involved in reward, emotion regulation, and cognition. These data further suggest ramifications of living in a disadvantaged neighborhood on brain health.
    Language English
    Publishing date 2023-09-15
    Publishing country England
    Document type Journal Article
    ISSN 2730-664X
    ISSN (online) 2730-664X
    DOI 10.1038/s43856-023-00350-5
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  7. Article ; Online: Multi-omics profiles of the intestinal microbiome in irritable bowel syndrome and its bowel habit subtypes.

    Jacobs, Jonathan P / Lagishetty, Venu / Hauer, Megan C / Labus, Jennifer S / Dong, Tien S / Toma, Ryan / Vuyisich, Momchilo / Naliboff, Bruce D / Lackner, Jeffrey M / Gupta, Arpana / Tillisch, Kirsten / Mayer, Emeran A

    Microbiome

    2023  Volume 11, Issue 1, Page(s) 5

    Abstract: Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is thought to involve alterations in the gut microbiome, but robust microbial signatures have been challenging to identify. As prior studies have primarily focused on ... ...

    Abstract Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is thought to involve alterations in the gut microbiome, but robust microbial signatures have been challenging to identify. As prior studies have primarily focused on composition, we hypothesized that multi-omics assessment of microbial function incorporating both metatranscriptomics and metabolomics would further delineate microbial profiles of IBS and its subtypes.
    Methods: Fecal samples were collected from a racially/ethnically diverse cohort of 495 subjects, including 318 IBS patients and 177 healthy controls, for analysis by 16S rRNA gene sequencing (n = 486), metatranscriptomics (n = 327), and untargeted metabolomics (n = 368). Differentially abundant microbes, predicted genes, transcripts, and metabolites in IBS were identified by multivariate models incorporating age, sex, race/ethnicity, BMI, diet, and HAD-Anxiety. Inter-omic functional relationships were assessed by transcript/gene ratios and microbial metabolic modeling. Differential features were used to construct random forests classifiers.
    Results: IBS was associated with global alterations in microbiome composition by 16S rRNA sequencing and metatranscriptomics, and in microbiome function by predicted metagenomics, metatranscriptomics, and metabolomics. After adjusting for age, sex, race/ethnicity, BMI, diet, and anxiety, IBS was associated with differential abundance of bacterial taxa such as Bacteroides dorei; metabolites including increased tyramine and decreased gentisate and hydrocinnamate; and transcripts related to fructooligosaccharide and polyol utilization. IBS further showed transcriptional upregulation of enzymes involved in fructose and glucan metabolism as well as the succinate pathway of carbohydrate fermentation. A multi-omics classifier for IBS had significantly higher accuracy (AUC 0.82) than classifiers using individual datasets. Diarrhea-predominant IBS (IBS-D) demonstrated shifts in the metatranscriptome and metabolome including increased bile acids, polyamines, succinate pathway intermediates (malate, fumarate), and transcripts involved in fructose, mannose, and polyol metabolism compared to constipation-predominant IBS (IBS-C). A classifier incorporating metabolites and gene-normalized transcripts differentiated IBS-D from IBS-C with high accuracy (AUC 0.86).
    Conclusions: IBS is characterized by a multi-omics microbial signature indicating increased capacity to utilize fermentable carbohydrates-consistent with the clinical benefit of diets restricting this energy source-that also includes multiple previously unrecognized metabolites and metabolic pathways. These findings support the need for integrative assessment of microbial function to investigate the microbiome in IBS and identify novel microbiome-related therapeutic targets. Video Abstract.
    MeSH term(s) Humans ; Gastrointestinal Microbiome/genetics ; Irritable Bowel Syndrome ; Multiomics ; RNA, Ribosomal, 16S/genetics ; Feces ; Habits
    Chemical Substances RNA, Ribosomal, 16S
    Language English
    Publishing date 2023-01-10
    Publishing country England
    Document type Video-Audio Media ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2697425-3
    ISSN 2049-2618 ; 2049-2618
    ISSN (online) 2049-2618
    ISSN 2049-2618
    DOI 10.1186/s40168-022-01450-5
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  8. Article ; Online: Mediators of the association between childhood trauma and pain sensitivity in adulthood: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network analysis.

    Pierce, Jennifer / Harte, Steven E / Afari, Niloofar / Bradley, Catherine S / Griffith, James W / Kim, Jayoung / Lutgendorf, Susan / Naliboff, Bruce D / Rodriguez, Larissa V / Taple, Bayley J / Williams, David / Harris, Richard E / Schrepf, Andrew

    Pain

    2023  Volume 164, Issue 9, Page(s) 1995–2008

    Abstract: Abstract: Urologic chronic pelvic pain syndrome (UCPPS) is a complex, debilitating condition in which patients often report nonpelvic pain in addition to localized pelvic pain. Understanding differential predictors of pelvic pain only vs widespread pain ...

    Abstract Abstract: Urologic chronic pelvic pain syndrome (UCPPS) is a complex, debilitating condition in which patients often report nonpelvic pain in addition to localized pelvic pain. Understanding differential predictors of pelvic pain only vs widespread pain may provide novel pathways for intervention. This study leveraged baseline data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network's Symptom Pattern Study to investigate the impact of childhood sexual and nonsexual violent trauma on pelvic and nonpelvic pain sensitivity among adult patients with UCPPS, as well as potential mediators of this association. Study participants who met inclusion criteria for UCPPS completed questionnaires assessing childhood and recent trauma, affective distress, cognitive dysfunction, and generalized sensory sensitivity. Experimental pain sensitivity was also evaluated using standardized pressure pain applied to the pubic region and the arm. Bivariate analyses showed that childhood violent trauma was associated with more nonviolent childhood trauma, more recent trauma, poorer adult functioning, and greater pain sensitivity at the pubic region, but not pain sensitivity at the arm. Path analysis suggested that childhood violent trauma was indirectly associated with pain sensitivity at both sites and that this indirect association was primarily mediated by generalized sensory sensitivity. More experiences of recent trauma also contributed to these indirect effects. The findings suggest that, among participants with UCPPS, childhood violent trauma may be associated with heightened pain sensitivity to the extent that trauma history is associated with a subsequent increase in generalized sensory sensitivity.
    MeSH term(s) Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Adverse Childhood Experiences/psychology ; Chronic Pain/diagnosis ; Chronic Pain/physiopathology ; Chronic Pain/psychology ; Pain Threshold/physiology ; Pelvic Pain/diagnosis ; Pelvic Pain/physiopathology ; Pelvic Pain/psychology ; Psychological Trauma/physiopathology ; Sexual Trauma/physiopathology
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000002895
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    Zs.A 1158: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Early and recent exposure to adversity, TLR-4 stimulated inflammation, and diurnal cortisol in women with interstitial cystitis/bladder pain syndrome: A MAPP research network study.

    Lutgendorf, Susan K / Zia, Sharaf / Luo, Yi / O'Donnell, Michael / van Bokhoven, Adrie / Bradley, Catherine S / Gallup, Robert / Pierce, Jennifer / Taple, Bayley J / Naliboff, Bruce D / Quentin Clemens, J / Kreder, Karl J / Schrepf, Andrew

    Brain, behavior, and immunity

    2023  Volume 111, Page(s) 116–123

    Abstract: Both early (ELA) and recent life adversity (RLA) have been linked with chronic pain conditions and persistent alterations of neuroendocrine and inflammatory responses. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic urologic disorder ... ...

    Abstract Both early (ELA) and recent life adversity (RLA) have been linked with chronic pain conditions and persistent alterations of neuroendocrine and inflammatory responses. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic urologic disorder characterized by bladder and/or pelvic pain, and excessive urinary frequency and/or urgency. IC/BPS has been associated with high levels of ELA as well as a distinct inflammatory signature. However, associations between ELA and RLA with inflammatory mechanisms in IC/BPS that might underlie the link between adversity and symptoms have not been examined. Here we investigated ELA and RLA in women with IC/BPS as potential risk factors for inflammatory processes and hypothalamic-pituitaryadrenal (HPA) abnormalities using data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Women with IC/BPS and healthy controls (n = 154 and 32, respectively) completed surveys, collected salivary cortisol at awakening and bedtime for 3 days, and gave a blood sample which was analyzed for 7 LPS-stimulated cytokines and chemokines (IL-6, TNFα, IL-1β, MIP1α, MCP1, IL-8, and IL-10). Two cytokine/chemokine composites were identified using principal components analysis. Patients with greater exposure to RLA or cumulative ELA and RLA of at least moderate severity showed elevated levels of a composite of all cytokines, adjusting for age, body mass index, and study site. Furthermore, there was a trending relationship between ELA and the pro-inflammatory composite score. Nocturnal cortisol and cortisol slope were not associated with ELA, RLA, or inflammation. The present findings support the importance of adverse events in IC/BPS via a biological mechanism and suggest that ELA and RLA should be assessed as risk factors for inflammation as part of a clinical workup for IC/BPS.
    MeSH term(s) Humans ; Female ; Cystitis, Interstitial/complications ; Cystitis, Interstitial/diagnosis ; Hydrocortisone ; Toll-Like Receptor 4 ; Inflammation/complications ; Pelvic Pain/complications ; Cytokines
    Chemical Substances Hydrocortisone (WI4X0X7BPJ) ; Toll-Like Receptor 4 ; Cytokines
    Language English
    Publishing date 2023-03-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2023.03.024
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  10. Article ; Online: Microbial and Metabolite Signatures of Stress Reactivity in Ulcerative Colitis Patients in Clinical Remission Predict Clinical Flare Risk.

    Jacobs, Jonathan P / Sauk, Jenny S / Ahdoot, Aaron I / Liang, Fengting / Katzka, William / Ryu, Hyo Jin / Khandadash, Ariela / Lagishetty, Venu / Labus, Jennifer S / Naliboff, Bruce D / Mayer, Emeran A

    Inflammatory bowel diseases

    2023  Volume 30, Issue 3, Page(s) 336–346

    Abstract: Background: Stress reactivity (SR) is associated with increased risk of flares in ulcerative colitis (UC) patients. Because both preclinical and clinical data support that stress can influence gut microbiome composition and function, we investigated ... ...

    Abstract Background: Stress reactivity (SR) is associated with increased risk of flares in ulcerative colitis (UC) patients. Because both preclinical and clinical data support that stress can influence gut microbiome composition and function, we investigated whether microbiome profiles of SR exist in UC.
    Methods: Ninety-one UC subjects in clinical and biochemical remission were classified into high and low SR groups by questionnaires. Baseline and longitudinal characterization of the intestinal microbiome was performed by 16S rRNA gene sequencing and fecal and plasma global untargeted metabolomics. Microbe, fecal metabolite, and plasma metabolite abundances were analyzed separately to create random forest classifiers for high SR and biomarker-derived SR scores.
    Results: High SR reactivity was characterized by altered abundance of fecal microbes, primarily in the Ruminococcaceae and Lachnospiraceae families; fecal metabolites including reduced levels of monoacylglycerols (endocannabinoid-related) and bile acids; and plasma metabolites including increased 4-ethyl phenyl sulfate, 1-arachidonoylglycerol (endocannabinoid), and sphingomyelin. Classifiers generated from baseline microbe, fecal metabolite, and plasma metabolite abundance distinguished high vs low SR with area under the receiver operating characteristic curve of 0.81, 0.83, and 0.91, respectively. Stress reactivity scores derived from these classifiers were significantly associated with flare risk during 6 to 24 months of follow-up, with odds ratios of 3.8, 4.1, and 4.9. Clinical flare and intestinal inflammation did not alter fecal microbial abundances but attenuated fecal and plasma metabolite differences between high and low SR.
    Conclusions: High SR in UC is characterized by microbial signatures that predict clinical flare risk, suggesting that the microbiome may contribute to stress-induced UC flares.
    MeSH term(s) Humans ; Colitis, Ulcerative ; Endocannabinoids ; RNA, Ribosomal, 16S ; Bile Acids and Salts ; Clostridiales
    Chemical Substances Endocannabinoids ; RNA, Ribosomal, 16S ; Bile Acids and Salts
    Language English
    Publishing date 2023-08-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 1340971-2
    ISSN 1536-4844 ; 1078-0998
    ISSN (online) 1536-4844
    ISSN 1078-0998
    DOI 10.1093/ibd/izad185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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