Single cell sequencing data identify distinct B cell and fibroblast populations in stricturing Crohn's disease.

Single cell RNA sequencing of human full thickness Crohn's disease (CD) small bowel resection specimens was used to identify potential therapeutic targets for stricturing (S) CD. Using an unbiased approach, 16 cell lineages were assigned within 14,539 sequenced cells from patient-matched SCD and non-stricturing (NSCD) preparations. SCD and NSCD contained identical cell types. Amongst immune cells, B cells and plasma cells were selectively increased in SCD samples. B cell subsets suggested formation of tertiary lymphoid tissue in SCD and compared with NSCD there was an increase in IgG, and a decrease in IgA plasma cells, consistent with their potential role in CD fibrosis. Two Lumican-positive fibroblast subtypes were identified and subclassified based on expression of selectively enriched genes as fibroblast clusters (C) 12 and C9. Cells within these clusters expressed the profibrotic genes Decorin (C12) and JUN (C9). C9 cells expressed ACTA2; ECM genes COL4A1, COL4A2, COL15A1, COL6A3, COL18A1 and ADAMDEC1; LAMB1 and GREM1. GO and KEGG Biological terms showed extracellular matrix and stricture organization associated with C12 and C9, and regulation of WNT pathway genes with C9. Trajectory and differential gene analysis of C12 and C9 identified four sub-clusters. Intra sub-cluster gene analysis detected 13 co-regulated gene modules that aligned along predicted pseudotime trajectories. CXCL14 and ADAMDEC1 were key markers in module 1. Our findings support further investigation of fibroblast heterogeneity and interactions with local and circulating immune cells at earlier time points in fibrosis progression. Breaking these interactions by targeting one or other population may improve therapeutic management for SCD.

Exploring the learning preferences of farmworker-serving community health workers.

Community health workers are responsible for finding, processing, and transferring health information to communities with limited access to health-related resources, including farmworkers. This paper is the culmination of an undergraduate student research project to explore the learning processes and preferences of farmworker-serving community health workers in the USA. The project was designed for students from farmworker or agricultural backgrounds at two North Carolina universities and was supported by a North Carolina Department of Health and Human Services workforce development grant. Semi-structured interviews were conducted, in person and virtually, with a convenience sample of 17 current and former community health workers. The interview data were analysed thematically and identified a preference for a combination of learning styles, with visual and hands-on learning being the most preferred. Community health workers also identified the importance of learning preferences in relation to their responsibilities as health educators. This study provides librarians, along with public health and medical professionals, with useful information about learning preferences to inform the creation of new and varied learning materials for community health workers.

Metformin in pregnancy and childhood neurodevelopmental outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes. DATA SOURCES: MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023. STUDY ELIGIBILITY CRITERIA: Studies of women who received treatment with metformin at any stage of pregnancy for any indication with neurodevelopmental data available for their offspring were included. Studies without a control group were excluded. Randomized controlled trials, case-control, cohort, and cross-sectional studies were included in the review. METHODS: Studies were screened for inclusion and data were extracted independently by 2 reviewers. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale for nonrandomized studies, and the Risk of Bias 2 tool for randomized trials. RESULTS: A total of 7 studies met the inclusion criteria, including a combined cohort of 14,042 children with 7641 children who were exposed and followed for up to 14 years of age. Metformin use during pregnancy was not associated with neurodevelopmental delay in infancy (relative risk, 1.09; 95% confidence interval, 0.54-2.17; 3 studies; 9668 children) or at ages 3 to 5 years (relative risk, 0.90; 95% confidence interval, 0.56-1.45; 2 studies; 6118 children). When compared with unexposed peers, metformin use during pregnancy was not associated with altered motor scores (mean difference, 0.30; 95% confidence interval, -1.15 to 1.74; 3 studies; 714 children) or cognitive scores (mean difference, -0.45; 95% confidence interval, -1.45 to 0.55; 4 studies; 734 children). Studies that were included were of high quality and deemed to be at low risk of bias. CONCLUSION: In utero exposure to metformin does not seem to be associated with adverse neurodevelopmental outcomes in children up to the age of 14 years. These findings provide reassurance to clinicians and pregnant women considering metformin use during pregnancy.

Accuracy of Information given by ChatGPT for patients with Inflammatory Bowel Disease in relation to ECCO Guidelines.

INTRODUCTION: As acceptance of AI platforms increases, more patients will consider these tools as sources of information. The ChatGPT architecture utilizes a neural network to process natural language, thus generating responses based on the context of input text. The accuracy and completeness of ChatGPT3.5 in the context of Inflammatory Bowel Disease remains unclear. METHODS: In this prospective study, 38 questions worded by IBD patients were inputted into ChatGPT3.5. The following topics were covered: 1) CD, UC and malignancy, 2) maternal medicine 3) infection and vaccination 4) complementary medicine. Responses given by Chat GPT were assessed for accuracy (1 - completely incorrect to 5 - completely correct) and completeness (3-point Likert scale; range 1 - incomplete to 3 - complete) by 14 expert gastroenterologists, in comparison with relevant ECCO guidelines. RESULTS: In terms of accuracy, most replies (84.2%) had a median score of ≥4 (IQR:2) and a mean score of 3.87 (SD: +/- 0.6). For completeness, 34.2% of the replies had a median score of 3 and 55.3 % had a median score of between 2 and <3. Overall, the mean rating was 2.24 (SD: +/- 0.4, Median:2 IQR :1). Though group 3 and 4 had a higher mean for both accuracy and completeness, there was no significant scoring variation between the 4 question groups (Kruskal-Wallis test p:>0.05). However, statistical analysis for the different individual questions revealed a significant difference both for accuracy (p<0.001) and completeness (p<0.001). The questions which rated the highest for both accuracy and completeness were related to smoking, while the lowest rating was related to screening for malignancy and vaccinations especially in the context of immunosuppression and family planning. CONCLUSION: This is the first study to demonstrate the capability of an AI-based system to provide accurate and comprehensive answers to real-world patient queries in IBD. AI systems may serve as a useful adjunct for patients, in addition to standard of care in clinic and validated patient information resources. However, responses in specialist areas may deviate from evidence-based guidance and the replies need to give more firm advice.

Human Intestinal Dendritic Cells Can Overcome Retinoic Acid Signaling to Generate Proinflammatory CD4 T Cells with Both Gut and Skin Homing Properties.

Retinoic acid, produced by intestinal dendritic cells (DCs), promotes T cell trafficking to the intestinal mucosa by upregulating α4ß7 integrin and inhibiting the generation of cutaneous leukocyte Ag (CLA) required for skin entry. In the present study, we report that activation of human naive CD4 T cells in an APC-free system generates cells expressing α4ß7 alone; in contrast, activation by intestinal DCs that produce retinoic acid and induce high levels of α4ß7 also results in CLA expression, generating CLA+α4ß7+ "dual tropic" cells, with both gut and skin trafficking potential, that also express high levels of α4ß1 integrin. DC generation of CLA+α4ß7+ T cells is associated with upregulation of FUT7, a fucosyltransferase involved in CLA generation; requires cell contact; and is enhanced by IL-12/IL-23. The blood CD4+ T cell population contains CLA+α4ß7+ cells, which are significantly enriched for cells capable of IFN-γ, IL-17, and TNF-α production compared with conventional CLA-α4ß7+ cells. Dual tropic lymphocytes are increased in intestinal tissue from patients with Crohn's disease, and single-cell RNA-sequencing analysis identifies a transcriptionally distinct cluster of FUT7-expressing cells present only in inflamed tissue; expression of genes associated with cell proliferation suggests that these cells are undergoing local activation. The expression of multiple trafficking molecules by CLA+α4ß7+ T cells can enable their recruitment by alternative pathways to both skin and gut; they may contribute to both intestinal and cutaneous manifestations of inflammatory bowel disease.

Epigenetic and metabolic reprogramming of fibroblasts in Crohn's disease strictures reveals histone deacetylases as therapeutic targets.

BACKGROUND & AIMS: No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterised fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies. METHODS: We undertook immunohistochemistry, metabolic, signalling pathway and Epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/ NSCD fibroblasts were cultured with TGFß and valproic acid [VPA]. RESULTS: Stricturing CD was characterised by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1, HDAC2, and HDAC7. As a proxy for HDAC activity, reduced numbers of H3K27ac+ cells were found in SCD compared to NSCD sections. Primary fibroblasts had increased extracellular lactate [increased glycolytic activity] and intracellular hydroxyproline [increased collagen production] in SCD compared to NSCD cultures. The metabolic effect of TGFß-stimulation was reversed by the HDAC inhibitor VPA. SCD fibroblasts appear "metabolically primed" and responded more strongly to both TGFß and VPA. Treatment with VPA revealed TGFß-dependent and independent Collagen-I production in CCD-18Co cells and primary fibroblasts. VPA altered the epigenetic landscape with reduced chromatin accessibility at the COL1A1 and COL1A2 promoters. CONCLUSIONS: Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype, and metabolic priming, characterise SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFß-mediated CD fibrosis. HDAC inhibitor therapy may 'reset' the epigenetic changes associated with fibrosis.

Prevalence of Perinatal Anxiety and Related Disorders in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Importance: Anxiety disorders are associated with poor maternal and neonatal outcomes. Women in low- and middle-income countries (LMICs) are thought to be disproportionally burdened by these disorders, yet their prevalence is unclear. Objective: To conduct a systematic review and meta-analysis to determine the prevalence of 6 anxiety and related disorders among perinatal women in LMICs. Data Sources: Embase, MEDLINE, PsycINFO, Cochrane Library, CINAHL, and Web of Science databases were searched from inception until September 7, 2023. Study Selection: Studies conducted in World Bank-defined LMICs and reporting prevalence of generalized anxiety disorder, obsessive-compulsive disorder, social anxiety disorder, posttraumatic stress disorder, panic disorder, or adjustment disorder during the perinatal period (conception to 12 months post partum) using a validated method were included. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Study eligibility, extracted data, and risk of bias of included studies were assessed by 2 independent reviewers. Random-effects meta-analysis was used to estimate pooled point prevalence. Subgroup analyses were performed by specific anxiety disorder. Main Outcomes and Measures: Main outcomes were prevalence estimates of each anxiety disorder, measured as percentage point estimates and corresponding 95% CIs. Results: At total of 10 617 studies were identified, 203 of which met the inclusion criteria and reported the outcomes of 212 318 women from 33 LMICs. Generalized anxiety disorder was the most reported (184 studies [90.6%]) and most prevalent disorder at 22.2% (95% CI, 19.4%-25.0%; n = 173 553). Posttraumatic stress disorder was the second most prevalent (8.3%; 95% CI, 5.0%-12.2%; 33 studies; n = 22 452). Adjustment disorder was least prevalent (2.9%; 95% CI, 0.0%-14.1%; 2 studies; n = 475). The prevalence of generalized anxiety varied by country income status, with the highest prevalence among lower-middle-income countries (27.6%; 95% CI, 21.6%-33.9%; 59 studies; n = 25 109), followed by low-income (24.0%; 95% CI, 15.3%-33.8%; 11 studies; n = 4961) and upper-middle-income (19.1%; 95% CI, 16.0%-22.4%; 110 studies; n = 138 496) countries. Conclusions and Relevance: These findings suggest that 1 in 5 women living in LMICs experience anxiety disorders during pregnancy and post partum. Targeted action is needed to reduce this high burden.

Methods matter: the influence of method on infection estimates of the bumblebee parasite Crithidia bombi.

The bumblebee gut parasite, Crithidia bombi, is widespread and prevalent in the field. Its interaction with Bombus spp. is a well-established epidemiological model. It is spread faecal-orally between colonies via the shared use of flowers when foraging. Accurately measuring the level of infection in bumblebees is important for assessing its distribution in the field, and also when conducting epidemiological experiments. Studies generally use 1 of 2 methods for measuring infection. One approach measures infection in faeces whereas the other method measures infection in guts. We tested whether the method of measuring infection affected the estimation of infection. Bumblebees were inoculated with a standardized inoculum and infection was measured 1 week later using either the faecal or gut method. We found that when the gut method was used to measure infection intensity estimates were significantly different to and approximately double those from the faecal method. These results have implications for the interpretation of previous study results and for the planning of future studies. Given the importance of bumblebees as pollinators, the impact of C. bombi on bumblebee health, and its use as an epidemiological model, we call on researchers to move towards consistent quantification of infections to enable future comparisons and meta-analyses of studies.

Transmission of a bumblebee parasite is robust despite parasite exposure to extreme temperatures.

All organisms are exposed to fluctuating environmental conditions, such as temperature. How individuals respond to temperature affects their interactions with one another. Changes to the interaction between parasites and their hosts can have a large effect on disease dynamics. The gut parasite, Crithidia bombi, can be highly prevalent in the bumblebee, Bombus terrestris, and is an established epidemiological model. The parasite is transmitted between bumblebees via flowers, exposing it to a range of environmental temperatures prior to infection. We investigated whether incubation duration and temperature exposure, prior to infection, affects parasite infectivity. Prior to inoculation in B. terrestris, C. bombi was incubated at 10, 20, 30, 40 or 50°C for either 10 or 60 min. These times were chosen to reflect the length of time that the parasite remains infective when outside the host and the rate of floral visitation in bumblebees. Prevalence and infection intensity were measured in bees 1 week later. Incubation duration and the interaction between incubation temperature and duration affected the prevalence of C. bombi at 50°C, resulting in no infections after 60 min. Below 50°C, C. bombi prevalence was not affected by incubation temperature or duration. Extreme temperatures induced morphological changes in C. bombi cells; however, infection intensity was not affected by incubation duration or temperature. These results highlight that this parasite is robust to a wide range of temperatures. The parasite was not infective after being exposed to 50°C for 60 min, such temperatures likely exceed the flight abilities of bumblebees, and thus the potential for transmission. This study shows the importance of understanding the effects of environmental conditions on both hosts and parasites, which is needed to predict transmission under different environmental conditions.

A paradox promoted by microglia cannibalism shortens the lifespan of developmental microglia.

The overproduction of cells and subsequent production of debris is a universal principle of neurodevelopment. Here we show an additional feature of the developing nervous system that causes neural debris - promoted by the sacrificial nature of embryonic microglia that irreversibly become phagocytic after clearing other neural debris. Described as long-lived, microglia colonize the embryonic brain and persist into adulthood. Using transgenic zebrafish to investigate the microglia debris during brain construction, we identified that unlike other neural cell-types that die in developmental stages after they have expanded, necroptotic-dependent microglial debris is prevalent when microglia are expanding in the zebrafish brain. Time-lapse imaging of microglia demonstrates that this debris is cannibalized by other microglia. To investigate features that promote microglia death and cannibalism, we used time-lapse imaging and fate-mapping strategies to track the lifespan of individual developmental microglia. These approaches revealed that instead of embryonic microglia being long-lived cells that completely digest their phagocytic debris, once most developmental microglia in zebrafish become phagocytic they eventually die, including ones that are cannibalistic. These results establish a paradox -- which we tested by increasing neural debris and manipulating phagocytosis -- that once most microglia in the embryo become phagocytic, they die, create debris and then are cannibalized by other microglia, resulting in more phagocytic microglia that are destined to die.

Prevalence of Perinatal Depression in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

Importance: Women who experience depression during or within a year of pregnancy are at increased risk of morbidity and mortality. Although those living in low- and middle-income countries are thought to be at increased risk of perinatal depression, the true prevalence remains unclear. Objective: To determine the prevalence of depression among individuals living in low- and middle-income countries during pregnancy and up 1 year post partum. Data Sources: MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and the Cochrane Library were searched from database inception until April 15, 2021. Study Selection: Studies were included that reported the prevalence of depression using a validated method during pregnancy or up to 12 months post partum in countries defined by the World Bank as low, lower-middle, and upper-middle income. Data Extraction and Synthesis: This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Two reviewers independently assessed study eligibility, extracted data, and assessed studies for bias. Prevalence estimates were calculated using a random-effects meta-analysis model. Subgroup analyses were performed among women who were considered at increased risk of developing perinatal depression. Main Outcomes and Measures: Point prevalence of perinatal depression was the main outcome measured as percentage point estimates with corresponding 95% CIs. Results: The search identified 8106 studies, of which data were extracted from 589 eligible studies reporting outcomes of 616 708 women from 51 countries. The pooled prevalence of perinatal depression across all studies was 24.7% (95% CI, 23.7%-25.6%). The prevalence of perinatal depression varied slightly by country income status. The highest prevalence was found in lower-middle-income countries, with a pooled prevalence of 25.5% (95% CI, 23.8%-27.1%; 197 studies from 23 countries including 212 103 individuals). In upper-middle-income countries, the pooled prevalence was 24.7% (95% CI, 23.6%-25.9%; 344 studies from 21 countries including 364 103 individuals) and in low-income countries, the pooled prevalence was 20.7% (95% CI, 18.4%-23.0%; 50 studies from 7 countries including 40 502 individuals). The East Asia and the Pacific region had the lowest prevalence of perinatal depression at 21.4% (95% CI, 19.8%-23.1%) and was significantly increased in the Middle East and North Africa at 31.5% (95% CI, 26.9%-36.2%; between-group comparison: P < .001). In subgroup analyses, the highest prevalence of perinatal depression was found among women who experienced intimate partner violence, at 38.9% (95% CI, 34.1%-43.6%). revalence of depression was also high among women with HIV (35.1% [95% CI, 29.6%-40.6%]) and those who had experienced a natural disaster (34.8% [95% CI, 29.4%-40.2%]). Conclusions and Relevance: This meta-analysis found that depression was common in low- and middle-income countries, affecting 1 in 4 perinatal women. Accurate estimates of the prevalence of perinatal depression in low- and middle-income countries are essential in informing policy, allocating scarce resources, and directing further research to improve outcomes for women, infants, and families.

Recruitment and Residence of Intestinal T Cells - Lessons for Therapy in Inflammatory Bowel Disease.

Targeting leukocyte trafficking in the management of inflammatory bowel disease [IBD] has been a significant therapeutic advance over the past 15 years. However, as with other advanced therapies, phase III clinical trials report response to trafficking inhibitors in only a proportion of patients, with fewer achieving clinical remission or mucosal healing. Additionally, there have been significant side effects, most notably progressive multifocal leukoencephalopathy in association with the α4 inhibitor natalizumab. This article reviews the mechanisms underpinning T cell recruitment and residence, to provide a background from which the strength and limitations of agents that disrupt leukocyte trafficking can be further explored. The therapeutic impact of trafficking inhibitors is underpinned by the complexity and plasticity of the intestinal immune response. Pathways essential for gut homing in health may be bypassed in the inflamed gut, thus providing alternative routes of entry when conventional homing molecules are targeted. Furthermore, there is conservation of trafficking architecture between proinflammatory and regulatory T cells. The persistence of resident memory cells within the gut gives rise to local established pro-inflammatory populations, uninfluenced by inhibition of trafficking. Finally, trafficking inhibitors may give rise to effects beyond the intended response, such as the impact of vedolizumab on innate immunity, as well as on target side effects. With significant research efforts into predictive biomarkers already underway, it is ultimately hoped that a better understanding of trafficking and residence will help us predict which patients are most likely to respond to inhibition of leukocyte trafficking, and how best to combine therapies.

Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease.

Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity and costs. The present study investigates the contribution of Wingless-Int-1 (Wnt) signalling to intestinal fibrogenesis, considers potential cross-talk between Wnt and transforming growth factor ß1 (TGFß) signalling pathways, and assesses the therapeutic potential of small-molecule Wnt inhibitors. ß-catenin expression was explored by immunohistochemistry (IHC) in formalin-fixed paraffin embedded (FFPE) tissue from patient-matched nonstrictured (NSCD) and strictured (SCD) intestine (n=6 pairs). Functional interactions between Wnt activation, TGFß signalling, and type I collagen (Collagen-I) expression were explored in CCD-18Co cells and primary CD myofibroblast cultures established from surgical resection specimens (n=16) using small-molecule Wnt inhibitors and molecular techniques, including siRNA-mediated gene knockdown, immunofluorescence (IF), Wnt gene expression arrays, and western blotting. Fibrotic SCD tissue was marked by an increase in ß-catenin-positive cells. In vitro, activation of Wnt-ß-catenin signalling increased Collagen-I expression in CCD-18Co cells. Conversely, ICG-001, an inhibitor of ß-catenin signalling, reduced Collagen-I expression in cell lines and primary CD myofibroblasts. TGFß increased ß-catenin protein levels but did not activate canonical Wnt signalling. Rather, TGFß up-regulated WNT5B, a noncanonical Wnt ligand, and the Wnt receptor FZD8, which contributed directly to the up-regulation of Collagen-I through a ß-catenin-independent mechanism. Treatment of CCD-18Co fibroblasts and patient-derived myofibroblasts with the FZD8 inhibitor 3235-0367 reduced extracellular matrix (ECM) expression. Our data highlight small-molecule Wnt inhibitors of both canonical and noncanonical Wnt signalling, as potential antifibrotic drugs to treat SCD intestinal fibrosis. They also highlight the importance of the cross-talk between Wnt and TGFß signalling pathways in CD intestinal fibrosis.

When pain is not the whole story: Presenting symptoms of women with endometriosis.

BACKGROUND: Endometriosis affects one in nine Australian women of reproductive age, and is often associated with pain and infertility. However, many women may be asymptomatic, or present with alternative symptoms. AIM: To identify reasons for initial specialist referral among patients with endometriosis. MATERIAL AND METHODS: Patients were identified as having endometriosis intraoperatively based on International Classification of Diseases coding. Operation reports were reviewed and graded for severity of disease. This cohort was then retrospectively audited to identify reasons for initial referral to the general gynaecology, endosurgery, gynae-oncology, reproductive medicine outpatient departments (OPD) at the Mercy Hospital for Women in Melbourne between 1 February 2015 and 31 December 2016. RESULTS: Three hundred patients were identified as having endometriosis at laparoscopy, including 90 women with Stage IV disease. Patients were a mean (SD) age of 33.1 (7.6) years. While pain remained a common reason for referral (61.7% of referrals), 36.7% of women with Grade IV disease did not have pain included in their referral letter. Severe disease was associated with increased age (regression coefficient 0.05; 95% CI: 0.03-0.07, P < 0.01), but not with pain symptoms. Women referred with ovarian cysts or masses were more likely to be diagnosed with severe disease (regression coefficient 0.69; 95% CI: 0.37-1.01, P < 0.01). CONCLUSION: Although pelvic pain is not a good predictor for a diagnosis of endometriosis, it remains a common symptom among women with the disease. However, more than one in three patients with Grade IV endometriosis presented without mention of pain symptoms, encouraging clinicians to adopt a broader approach to the presenting symptoms of endometriosis.

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.

This is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.

UK IBD Twin Registry: Concordance and Environmental Risk Factors of Twins with IBD.

BACKGROUND AND AIMS: Twin studies have long been used to infer heritability. Within the 'omics era, twin cohorts have even greater research potential. This study describes the formation of the UK IBD Twin Registry and analysis of concordance and environmental factors. METHOD: Twin pairs with IBD were recruited by advertising via IBD charities and social media, re-tracing a dormant IBD database and clinician referral. Details of zygosity, concordance, disease history and environmental factors were assessed. Pair concordance was calculated, and environmental factors were analysed with logistic regression models adjusted for zygosity and concordance. RESULTS: Ninety-one twin pairs were included in the analysis; forty-two with CD and forty-nine with UC. More MZ twin pairs with CD were concordant compared with DZ pairs, thus inferring heritability (Chi-sq. 15.6. P < 0.001). In UC, MZ concordance was also numerically greater. Cigarette smoking was predictive of CD (OR 2.66, 95% CI 1.16 to 6.07 P = 0.02); there may be an independent association with cannabis smoking (OR 2.59 95% CI 0.89 to 7.55 P = 0.08). Breastfeeding was protective against UC (OR 0.48, 95% CI 0.25-0.93, P = 0.03), but not CD. Self-reports of less occurrences of gastroenteritis than peers were protective against future UC onset (OR 0.33 95% CI 0.15 to 0.74, P = 0.01). Method of delivery, parental attitudes towards hygiene and recall of diet did not impact future IBD concordance. CONCLUSIONS: This study supports the heritability of IBD. Twin study analysis was able to elucidate environmental factors associated with IBD.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.