Background: Obesity affects hormone metabolisms and contributes to gallstone disease more strongly in women than in men. This study assessed the sex-specific associations between serum levels of sex hormone-binding globulin (SHBG) and testosterone and risk of cholecystectomy, and their mediation role in the obesity-cholecystectomy association. Methods: Included were 176,909 men and 160,147 women from the UK Biobank. Serum SHBG and total testosterone were measured by immunoassay. Incident cases of cholecystectomy for gallstone disease were identified using hospital inpatient records. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) of cholecystectomy associated with the serum hormones. A mediation analysis was performed to estimate the proportion of the obesity-cholecystectomy association potentially mediated by the two sex hormones. Results: A total of 2877 men and 4607 women underwent cholecystectomies during the follow-up. Regardless of sex, higher levels of SHBG were associated with a lower risk of cholecystectomy. The HRs of cholecystectomy comparing the highest with the lowest quartiles of SHBG were 0.68 (95% CI: 0.59-0.77) in men (P-trend <0.001) and 0.39 (95% CI: 0.36-0.53) in women (P-trend <0.001). Higher levels of testosterone were associated with a higher risk of cholecystectomy in women (HRQ4 vs. Q1 = 1.28; 95% CI: 1.18-1.39; P-trend <0.001) but not in men (P-trend = 0.12). In women, it was estimated that 14.71% and 2.74% of the association between obesity and cholecystectomy was significantly medicated by SHBG and testosterone, respectively. Conclusions: SHBG levels are inversely associated with risk of cholecystectomy in both sexes, whereas higher testosterone levels are associated with a higher risk of cholecystectomy only in women. Both hormones mediate the obesity-cholecystectomy association in women.
{"title":"Sex hormones, obesity, and risk of cholecystectomy in men and women: a population-based prospective study and mediation analysis","authors":"Jie-Qiong Lyu, Wei Jiang, Yi-Ping Jia, Meng-Yuan Miao, Jia-Min Wang, Hao-Wei Tao, Miao Zhao, Yong-Fei Hua, Guo-Chong Chen","doi":"10.1101/2024.02.19.24303068","DOIUrl":"https://doi.org/10.1101/2024.02.19.24303068","url":null,"abstract":"Background: Obesity affects hormone metabolisms and contributes to gallstone disease more strongly in women than in men. This study assessed the sex-specific associations between serum levels of sex hormone-binding globulin (SHBG) and testosterone and risk of cholecystectomy, and their mediation role in the obesity-cholecystectomy association. Methods: Included were 176,909 men and 160,147 women from the UK Biobank. Serum SHBG and total testosterone were measured by immunoassay. Incident cases of cholecystectomy for gallstone disease were identified using hospital inpatient records. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) of cholecystectomy associated with the serum hormones. A mediation analysis was performed to estimate the proportion of the obesity-cholecystectomy association potentially mediated by the two sex hormones. Results: A total of 2877 men and 4607 women underwent cholecystectomies during the follow-up. Regardless of sex, higher levels of SHBG were associated with a lower risk of cholecystectomy. The HRs of cholecystectomy comparing the highest with the lowest quartiles of SHBG were 0.68 (95% CI: 0.59-0.77) in men (P-trend <0.001) and 0.39 (95% CI: 0.36-0.53) in women (P-trend <0.001). Higher levels of testosterone were associated with a higher risk of cholecystectomy in women (HRQ4 vs. Q1 = 1.28; 95% CI: 1.18-1.39; P-trend <0.001) but not in men (P-trend = 0.12). In women, it was estimated that 14.71% and 2.74% of the association between obesity and cholecystectomy was significantly medicated by SHBG and testosterone, respectively. Conclusions: SHBG levels are inversely associated with risk of cholecystectomy in both sexes, whereas higher testosterone levels are associated with a higher risk of cholecystectomy only in women. Both hormones mediate the obesity-cholecystectomy association in women.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"124 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139910915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-20DOI: 10.1101/2024.02.17.23300358
Lianne Lewis, Callum Michie, Alexander Sheppard, Millicent Stone, George Macfaul, Joe Harrison
Objective This audit examines the impact of a recently-commissioned clinician and patient support tool, on care pathways for Inflammatory Bowel Disease patients at Milton Keynes University Hospital, on follow up appointments (including PIFUs), associated cost savings and patient and clinician engagement and experience. Design The audit was conducted using a retrospective, consecutive case review of appointment records of patients enrolled onto the iOWNA platform during a 9-month audit period. Patient-clinician interactions were categorised depending on whether an appointment was saved and an appropriate nursing time saving logged. Data on both cost savings and PIFU numbers were also collected from the trust. Quantitative and qualitative feedback of clinician and patient experience were captured. Results The deployment of iOWNA resulted in a total time saving of 14,735 minutes across the audit period, of which 9,280 minutes comprised savings on in-person appointments, representing 232 appointments saved. The cost savings for these 232 replaced appointments totalled 16,704 GBP. The audit period also saw a statistically significant (p<0.01) increase in the number of Patient-Initiated Follow Ups (PIFUs). Patient and clinician surveys reflected positive experiences of the new care pathway among all service users. Conclusion The results of the audit demonstrate the important role digital tools can play in transforming existing care pathways to deal with the widespread challenges facing the NHS following the COVID-19 pandemic, with annual savings of over 345 million GBP for the NHS if the appointment cost savings demonstrated in this audit were replicated alongside a 5% reduction nationally in outpatient attendances.
{"title":"Audit of Impact of a Clinician & Patient Support Tool in a Nurse-led Clinic for Inflammatory Bowel Disease Service at Milton Keynes University Hospital","authors":"Lianne Lewis, Callum Michie, Alexander Sheppard, Millicent Stone, George Macfaul, Joe Harrison","doi":"10.1101/2024.02.17.23300358","DOIUrl":"https://doi.org/10.1101/2024.02.17.23300358","url":null,"abstract":"Objective\u0000This audit examines the impact of a recently-commissioned clinician and patient support tool, on care pathways for Inflammatory Bowel Disease patients at Milton Keynes University Hospital, on follow up appointments (including PIFUs), associated cost savings and patient and clinician engagement and experience. Design\u0000The audit was conducted using a retrospective, consecutive case review of appointment records of patients enrolled onto the iOWNA platform during a 9-month audit period. Patient-clinician interactions were categorised depending on whether an appointment was saved and an appropriate nursing time saving logged. Data on both cost savings and PIFU numbers were also collected from the trust. Quantitative and qualitative feedback of clinician and patient experience were captured. Results\u0000The deployment of iOWNA resulted in a total time saving of 14,735 minutes across the audit period, of which 9,280 minutes comprised savings on in-person appointments, representing 232 appointments saved. The cost savings for these 232 replaced appointments totalled 16,704 GBP. The audit period also saw a statistically significant (p<0.01) increase in the number of Patient-Initiated Follow Ups (PIFUs). Patient and clinician surveys reflected positive experiences of the new care pathway among all service users. Conclusion\u0000The results of the audit demonstrate the important role digital tools can play in transforming existing care pathways to deal with the widespread challenges facing the NHS following the COVID-19 pandemic, with annual savings of over 345 million GBP for the NHS if the appointment cost savings demonstrated in this audit were replicated alongside a 5% reduction nationally in outpatient attendances.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139910725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-13DOI: 10.1101/2024.02.11.24302644
Kevin Liu, Moniyka Sachar, Violeta Popov, Zhiheng Pei, Giulio Quarta
Sessile serrated lesions (SSLs) are a class of colon polyps which are challenging to detect through current screening methods but are highly associated with colon cancer. We reasoned that a biomarker sensitive for SSLs would be clinically useful to improve detection. Recent endoscopic and histopathologic studies suggest that SSLs are associated with alterations in intestinal mucin expression but the frequency with which this occurs is not known. We performed a meta-analysis of available pathologic studies comparing mucin expression on SSLs to normal colonic mucosa, tubular adenomas (TAs), villous adenomas (VAs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). We searched Medline, Pubmed, and Embase and found 440 publications in this topic, and 18 total studies met inclusion. We found that MUC5AC expression was more common in SSLs compared to normal colonic mucosa (OR=82.9, p<0.01), TAs (OR=11, p<0.01), and TSAs (OR=3.6, p=0.04). We found no difference in MUC5AC expression between SSLs versus HPs (OR=2.1, p=0.09) and no difference in MUC5AC expression between left colon and right colon HPs, with an OR=1.8, p=0.23. We found that MUC5AC expression was found commonly on VAs, SSLs, and TSAs while the frequency on colon cancers declined. MUC5AC is also upregulated in inflammatory bowel disease and in response to intestinal infections. MUC5AC expression highlights the potential of mucins as sensitive biomarkers, though not specific to SSLs. Further research into the clinical utilization of MUC5AC could enhance SSL detection.
{"title":"Mucin 5AC is a sensitive surface marker for sessile serrated lesions: results from a systematic review and meta-analysis","authors":"Kevin Liu, Moniyka Sachar, Violeta Popov, Zhiheng Pei, Giulio Quarta","doi":"10.1101/2024.02.11.24302644","DOIUrl":"https://doi.org/10.1101/2024.02.11.24302644","url":null,"abstract":"Sessile serrated lesions (SSLs) are a class of colon polyps which are challenging to detect through current screening methods but are highly associated with colon cancer. We reasoned that a biomarker sensitive for SSLs would be clinically useful to improve detection. Recent endoscopic and histopathologic studies suggest that SSLs are associated with alterations in intestinal mucin expression but the frequency with which this occurs is not known. We performed a meta-analysis of available pathologic studies comparing mucin expression on SSLs to normal colonic mucosa, tubular adenomas (TAs), villous adenomas (VAs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). We searched Medline, Pubmed, and Embase and found 440 publications in this topic, and 18 total studies met inclusion. We found that MUC5AC expression was more common in SSLs compared to normal colonic mucosa (OR=82.9, p<0.01), TAs (OR=11, p<0.01), and TSAs (OR=3.6, p=0.04). We found no difference in MUC5AC expression between SSLs versus HPs (OR=2.1, p=0.09) and no difference in MUC5AC expression between left colon and right colon HPs, with an OR=1.8, p=0.23. We found that MUC5AC expression was found commonly on VAs, SSLs, and TSAs while the frequency on colon cancers declined. MUC5AC is also upregulated in inflammatory bowel disease and in response to intestinal infections. MUC5AC expression highlights the potential of mucins as sensitive biomarkers, though not specific to SSLs. Further research into the clinical utilization of MUC5AC could enhance SSL detection.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.1101/2024.02.05.24302343
Daniel S. Levic, Donna Niedzwiecki, Apoorva Kandakatla, Norah S. Karlovich, Arjun Juneja, Jieun Park, Christina Stolarchuk, Shanté Adams, Jason R. Willer, Matthew R. Schaner, Grace Lian, Caroline Beasley, Lindsay Marjoram, Ann D. Flynn, John F. Valentine, Jane E. Onken, Shehzad Z. Sheikh, Erica E. Davis, Kimberley J. Evason, Katherine S. Garman, Michel Bagnat
Background and aims Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions influenced heavily by environmental factors. DNA methylation is a form of epigenetic regulation linking environmental stimuli to gene expression changes and inflammation. Here, we investigated how DNA methylation of the TNF promoter differs between inflamed and uninflamed mucosa of IBD patients, including anti-TNF responders and non-responders.
背景和目的 炎症性肠病（IBD）是受环境因素严重影响的慢性炎症性疾病。DNA 甲基化是一种表观遗传调控形式，它将环境刺激与基因表达变化和炎症联系在一起。在此，我们研究了 IBD 患者（包括抗肿瘤坏死因子应答者和非应答者）有炎症和无炎症粘膜之间 TNF 启动子 DNA 甲基化的差异。
{"title":"TNF promoter hypomethylation is associated with mucosal inflammation in IBD and anti-TNF response","authors":"Daniel S. Levic, Donna Niedzwiecki, Apoorva Kandakatla, Norah S. Karlovich, Arjun Juneja, Jieun Park, Christina Stolarchuk, Shanté Adams, Jason R. Willer, Matthew R. Schaner, Grace Lian, Caroline Beasley, Lindsay Marjoram, Ann D. Flynn, John F. Valentine, Jane E. Onken, Shehzad Z. Sheikh, Erica E. Davis, Kimberley J. Evason, Katherine S. Garman, Michel Bagnat","doi":"10.1101/2024.02.05.24302343","DOIUrl":"https://doi.org/10.1101/2024.02.05.24302343","url":null,"abstract":"<strong>Background and aims</strong> Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions influenced heavily by environmental factors. DNA methylation is a form of epigenetic regulation linking environmental stimuli to gene expression changes and inflammation. Here, we investigated how DNA methylation of the <em>TNF</em> promoter differs between inflamed and uninflamed mucosa of IBD patients, including anti-TNF responders and non-responders.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-04DOI: 10.1101/2024.02.03.24302160
Matthew K Schroeder, Suha Abushamma, Alvin T George, Ravella Balakrishna, John Hickman, Anusha Elumalai, Paul Wise, Maria Zulfiqar, Daniel R Ludwig, Anup Shetty, Satish E Viswanath, Chongliang Luo, Shaji Sebastian, David Ballard, Parakkal Deepak
Background and Aims: Perianal fistulizing Crohn's disease (CD-PAF) is an aggressive phenotype of Crohn's disease (CD) defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by Geldof et al. that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. Methods: We identified all patients with CD-PAF and at least one baseline and one follow-up pelvic (pMRI). Geldof Classification, disease characteristics, and imaging indices were collected retrospectively at time-periods corresponding with respective MRIs. Results: We identified 100 patients with CD-PAF of which 96 were assigned Geldof Classes 1-2c at baseline. Most patients (78.1%) started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex (72.0%, 46.6%, 40.0%, p = 0.03) and prior perianal surgery (52.0% vs 44.6% vs 40.0%, p = 0.02) were more frequently observed in those with improved. Baseline pMRI indices were not associated with changes in classification, however, greater improvements in mVAI, MAGNIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modeling identified only male sex (-0.31, 95% CI -0.60 to -0.02) with improvement in class. Conclusion: Geldof classification highlights the dynamic nature of CDPAF over time, however, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower Geldof classification. Keywords: Crohn's disease; perianal fistula; classification system; pelvic MRI
{"title":"Geldof Expert Consensus Classification of Perianal Fistulizing Crohn's Disease: A Real-World Application in a Serial Fistula MRI Cohort","authors":"Matthew K Schroeder, Suha Abushamma, Alvin T George, Ravella Balakrishna, John Hickman, Anusha Elumalai, Paul Wise, Maria Zulfiqar, Daniel R Ludwig, Anup Shetty, Satish E Viswanath, Chongliang Luo, Shaji Sebastian, David Ballard, Parakkal Deepak","doi":"10.1101/2024.02.03.24302160","DOIUrl":"https://doi.org/10.1101/2024.02.03.24302160","url":null,"abstract":"Background and Aims: Perianal fistulizing Crohn's disease (CD-PAF) is an aggressive phenotype of Crohn's disease (CD) defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by Geldof et al. that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. Methods: We identified all patients with CD-PAF and at least one baseline and one follow-up pelvic (pMRI). Geldof Classification, disease characteristics, and imaging indices were collected retrospectively at time-periods corresponding with respective MRIs. Results: We identified 100 patients with CD-PAF of which 96 were assigned Geldof Classes 1-2c at baseline. Most patients (78.1%) started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex (72.0%, 46.6%, 40.0%, p = 0.03) and prior perianal surgery (52.0% vs 44.6% vs 40.0%, p = 0.02) were more frequently observed in those with improved. Baseline pMRI indices were not associated with changes in classification, however, greater improvements in mVAI, MAGNIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modeling identified only male sex (-0.31, 95% CI -0.60 to -0.02) with improvement in class. Conclusion: Geldof classification highlights the dynamic nature of CDPAF over time, however, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower Geldof classification. Keywords: Crohn's disease; perianal fistula; classification system; pelvic MRI","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139678811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1101/2024.02.01.24301982
Ryan Marsh, Claudio Dos Santos, Alexander Yule, Neele S Dellschaft, Caroline L Hoad, Christabella Ng, Giles Major, Alan R Smyth, Damian Rivett, Christopher van der Gast
Background: There is a paucity of knowledge on the longer-term effects of CF transmembrane conductance regulator (CFTR) modulator therapies upon the gut microbiome and associated outcomes. In a pilot study, we investigated longitudinal Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy on the gut microbiota, metabolomic functioning, and clinical outcomes in people with CF (pwCF). Study design: Faecal samples from 20 pwCF were acquired before and then following 3, 6, and 17+ months of ETI therapy. Samples were subjected to microbiota sequencing and targeted metabolomics to profile and quantify short-chain fatty acid composition. Ten healthy matched controls were included for comparison. Clinical data, including markers of intestinal function were integrated to investigate relationships. Results: Extended ETI therapy increased core microbiota diversity and composition, which translated to gradual shifts in whole microbiota composition towards that observed in healthy controls. Despite becoming more similar over time, CF microbiota and functional metabolite compositions remained significantly different to healthy controls. Antibiotic treatment for pulmonary infection significantly explained a relatively large degree of variation within the whole microbiota and rarer satellite taxa. Clinical outcomes were not significantly different following ETI. Conclusions: A positive trajectory towards the microbiota observed in healthy controls was found. However, we posit that progression was predominately impeded by pulmonary antibiotics administration. We recommend future studies use integrated omics approaches within a combination of long-term longitudinal patient studies and model experimental systems. This will deepen our understanding of the impacts of CFTR modulator therapy and respiratory antibiotic interventions upon the gut microbiome and gastrointestinal pathophysiology in CF.
{"title":"Impact of extended Elexacaftor/Tezacaftor/Ivacaftor therapy on the gut microbiome in cystic fibrosis","authors":"Ryan Marsh, Claudio Dos Santos, Alexander Yule, Neele S Dellschaft, Caroline L Hoad, Christabella Ng, Giles Major, Alan R Smyth, Damian Rivett, Christopher van der Gast","doi":"10.1101/2024.02.01.24301982","DOIUrl":"https://doi.org/10.1101/2024.02.01.24301982","url":null,"abstract":"Background: There is a paucity of knowledge on the longer-term effects of CF transmembrane conductance regulator (CFTR) modulator therapies upon the gut microbiome and associated outcomes. In a pilot study, we investigated longitudinal Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy on the gut microbiota, metabolomic functioning, and clinical outcomes in people with CF (pwCF). Study design: Faecal samples from 20 pwCF were acquired before and then following 3, 6, and 17+ months of ETI therapy. Samples were subjected to microbiota sequencing and targeted metabolomics to profile and quantify short-chain fatty acid composition. Ten healthy matched controls were included for comparison. Clinical data, including markers of intestinal function were integrated to investigate relationships. Results: Extended ETI therapy increased core microbiota diversity and composition, which translated to gradual shifts in whole microbiota composition towards that observed in healthy controls. Despite becoming more similar over time, CF microbiota and functional metabolite compositions remained significantly different to healthy controls. Antibiotic treatment for pulmonary infection significantly explained a relatively large degree of variation within the whole microbiota and rarer satellite taxa. Clinical outcomes were not significantly different following ETI. Conclusions: A positive trajectory towards the microbiota observed in healthy controls was found. However, we posit that progression was predominately impeded by pulmonary antibiotics administration. We recommend future studies use integrated omics approaches within a combination of long-term longitudinal patient studies and model experimental systems. This will deepen our understanding of the impacts of CFTR modulator therapy and respiratory antibiotic interventions upon the gut microbiome and gastrointestinal pathophysiology in CF.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1101/2024.01.31.24302084
Andrea Shin, Yue Xing, Mohammed Rayyan Waseem, Robert Siwiec, Toyia James-Stevenson, Nicholas Rogers, Matthew Bohm, John Wo, Carolyn Lockett, Anita Gupta, Jhalka Kadariya, Evelyn Toh, Rachel Anderson, Huiping Xu, Xiang Gao
Objective: Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes. Design: We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM). Results: Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including Dorea sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM. Conclusion: Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers.
{"title":"Microbiota-Short Chain Fatty Acid Relationships and Microbial Substrate Preferences Vary Across the Spectrum of Irritable Bowel Syndrome (IBS)","authors":"Andrea Shin, Yue Xing, Mohammed Rayyan Waseem, Robert Siwiec, Toyia James-Stevenson, Nicholas Rogers, Matthew Bohm, John Wo, Carolyn Lockett, Anita Gupta, Jhalka Kadariya, Evelyn Toh, Rachel Anderson, Huiping Xu, Xiang Gao","doi":"10.1101/2024.01.31.24302084","DOIUrl":"https://doi.org/10.1101/2024.01.31.24302084","url":null,"abstract":"Objective: Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes. Design: We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM). Results: Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including Dorea sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM. Conclusion: Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139667182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is probable that people who have celiac disease (CD) are more likely to have thyroid disorders. A comprehensive systematic review and meta-analysis were conducted to assess the link between thyroid disorders and CD. Articles were selected from PubMed, Web of Science, Scopus, Ovid, Embase, Cochrane, ProQuest, and Wiley from February 2022 and earlier. A meta-analysis was conducted to evaluate the outcomes, using odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). The meta-analysis comprised 31 articles with 3310256 participants including 101253 individuals with thyroid disorders. Overall, the frequency of thyroid disease was notably higher in patients with CD compared to the control groups (OR: 3.06, 95% CI: 2.51 – 3.72, P<0.001). The findings of our meta-analysis support the notion that patients with CD are more likely to have autoimmune thyroid disease (ATD) and other thyroid disorders than the control group, thus indicating that regular screening for thyroid disease is necessary for CD patients. Further cohort research is required to investigate the relationship between thyroid disorders and CD.
患有乳糜泻（CD）的人更有可能患有甲状腺疾病。为了评估甲状腺疾病与乳糜泻之间的联系，我们进行了一项全面的系统综述和荟萃分析。文章选自2022年2月及以前的PubMed、Web of Science、Scopus、Ovid、Embase、Cochrane、ProQuest和Wiley。采用几率比（OR）和相应的 95% 置信区间（95% CI）进行荟萃分析，以评估结果。荟萃分析包括31篇文章，3310256名参与者，其中101253人患有甲状腺疾病。总体而言，与对照组相比，CD患者患甲状腺疾病的频率明显更高（OR：3.06，95% CI：2.51 - 3.72，P<0.001）。我们的荟萃分析结果支持了这样一种观点，即与对照组相比，CD患者更有可能患有自身免疫性甲状腺疾病（ATD）和其他甲状腺疾病，从而表明有必要对CD患者进行定期的甲状腺疾病筛查。要进一步研究甲状腺疾病与CD之间的关系，还需要进一步的队列研究。
{"title":"A Systematic Review and Meta-analysis for Association of Celiac Disease and Thyroid Disorders","authors":"Fatemeh Hasani, Zahra Norouzi, Sima Besharat, Hesamaddin Shirzad-Aski, Somayeh Ghorbani, Masoud Mohammadi, Anahita Yadegari, Ali Kalhori","doi":"10.1101/2024.01.26.24301845","DOIUrl":"https://doi.org/10.1101/2024.01.26.24301845","url":null,"abstract":"It is probable that people who have celiac disease (CD) are more likely to have thyroid disorders. A comprehensive systematic review and meta-analysis were conducted to assess the link between thyroid disorders and CD. Articles were selected from PubMed, Web of Science, Scopus, Ovid, Embase, Cochrane, ProQuest, and Wiley from February 2022 and earlier. A meta-analysis was conducted to evaluate the outcomes, using odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). The meta-analysis comprised 31 articles with 3310256 participants including 101253 individuals with thyroid disorders. Overall, the frequency of thyroid disease was notably higher in patients with CD compared to the control groups (OR: 3.06, 95% CI: 2.51 – 3.72, P<0.001). The findings of our meta-analysis support the notion that patients with CD are more likely to have autoimmune thyroid disease (ATD) and other thyroid disorders than the control group, thus indicating that regular screening for thyroid disease is necessary for CD patients. Further cohort research is required to investigate the relationship between thyroid disorders and CD.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population. Design: The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n=112) and colonic tissue (n=36) in 112 individuals. Of these had CRC (n=24), premalignant lesions (n=10), healthy individuals (n=50) and in those with diabetes (n=28). Results: Overall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium, were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p< 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes. Conclusion: Despite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, with Prevotella species, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population.
{"title":"Metagenomic analysis of colonic tissue and stool microbiome in patients with colorectal cancer in a South Asian population","authors":"Bawantha Gamage, Diyanath Ranasinghe, Promoda Sahankumari, Gathsaurie Neelika Malavige","doi":"10.1101/2024.01.25.24301775","DOIUrl":"https://doi.org/10.1101/2024.01.25.24301775","url":null,"abstract":"Objective: The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population. Design: The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n=112) and colonic tissue (n=36) in 112 individuals. Of these had CRC (n=24), premalignant lesions (n=10), healthy individuals (n=50) and in those with diabetes (n=28). Results: Overall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium, were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p< 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes. Conclusion: Despite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, with Prevotella species, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.1101/2024.01.22.24301559
Xiaoxuan Liu, Thomas Walters, Iram Siddiqui, Oscar Lopez-Nunez, Surya Prasath, Lee A Denson, PROTECT consortium, Jasbir Dhaliwal
Background and Aims: We previously reported clinical features associated with outcomes in pediatric ulcerative colitis (UC). Here we developed a histopathology model to predict corticosteroid-free remission (CSFR) on mesalamine therapy alone. Methods: Pre-treatment rectal biopsy slides were digitized in training and validation groups of 292 and 113 pediatric UC patients, respectively. Whole slide images (WSI) underwent pre-processing. Thirteen machine learning (ML) models were trained using 250 histomic features including texture, color, histogram, and nuclei. Feature importance was determined by the Gini index with the classifier re-trained using the top features. Results: 187571 informative patches from 292 training group patients (Male:53%; Age:13y (IQR:11-15); CSFR:41%) were trained on 13 ML classifiers. The best model was random forest (RF). Eighteen optimal histomic features were identified and trained, and the corresponding WSI AUROC was 0.89 (95%CI:0.71, 0.96), accuracy of 90% for CSFR. Features were re-trained on an independent real-world dataset of 113 patients and the model WSI AUROC was 0.85 (95%CI:0.75, 0.95), accuracy of 85%. Conclusion: Routine histopathology obtained at diagnosis contains histomic features associated with both UC treatment responses and underlying mechanisms of disease.
{"title":"Machine Learning-Based Prediction of Pediatric Ulcerative Colitis Treatment Response using Diagnostic Histopathology","authors":"Xiaoxuan Liu, Thomas Walters, Iram Siddiqui, Oscar Lopez-Nunez, Surya Prasath, Lee A Denson, PROTECT consortium, Jasbir Dhaliwal","doi":"10.1101/2024.01.22.24301559","DOIUrl":"https://doi.org/10.1101/2024.01.22.24301559","url":null,"abstract":"Background and Aims: We previously reported clinical features associated with outcomes in pediatric ulcerative colitis (UC). Here we developed a histopathology model to predict corticosteroid-free remission (CSFR) on mesalamine therapy alone. Methods: Pre-treatment rectal biopsy slides were digitized in training and validation groups of 292 and 113 pediatric UC patients, respectively. Whole slide images (WSI) underwent pre-processing. Thirteen machine learning (ML) models were trained using 250 histomic features including texture, color, histogram, and nuclei. Feature importance was determined by the Gini index with the classifier re-trained using the top features. Results: 187571 informative patches from 292 training group patients (Male:53%; Age:13y (IQR:11-15); CSFR:41%) were trained on 13 ML classifiers. The best model was random forest (RF). Eighteen optimal histomic features were identified and trained, and the corresponding WSI AUROC was 0.89 (95%CI:0.71, 0.96), accuracy of 90% for CSFR. Features were re-trained on an independent real-world dataset of 113 patients and the model WSI AUROC was 0.85 (95%CI:0.75, 0.95), accuracy of 85%. Conclusion: Routine histopathology obtained at diagnosis contains histomic features associated with both UC treatment responses and underlying mechanisms of disease.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139560758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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