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227 results on '"Walter, Susanna"'

1. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author

Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I, Raygoza Garay, Juan Antonio, Finnicum, Casey T, Liu, Xingrong, Zhernakova, Daria V, Bonder, Marc Jan, Hansen, Tue H, Frost, Fabian, Rühlemann, Malte C, Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A, Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D, Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T, Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I, Burk, Robert D, Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E, van Duijn, Cornelia M, Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A, Ijzerman, Richard G, Jackson, Matthew A, Jaddoe, Vincent WV, Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J, Lieb, Wolfgang, Lusis, Aldons J, Masclee, Ad AM, Moll, Henriette A, Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J, Steves, Claire J, Thorsen, Jonathan, Timpson, Nicholas J, Tito, Raul Y, Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H, Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U, Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy MAE, Arias Vasquez, Alejandro, de Geus, Eco JC, Meyer, Katie A, Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C, Spector, Tim D, Uitterlinden, Andre G, Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M, Franke, Lude, Sanna, Serena, D’Amato, Mauro, and Pedersen, Oluf

Subjects
Microbiology, Biological Sciences, Genetics, Human Genome, Biotechnology, Clinical Research, Digestive Diseases, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Adolescent, Adult, Bifidobacterium, Child, Child, Preschool, Cohort Studies, Female, Gastrointestinal Microbiome, Genetic Variation, Genome-Wide Association Study, Humans, Lactase, Linkage Disequilibrium, Male, Mendelian Randomization Analysis, Metabolism, Quantitative Trait Loci, RNA, Ribosomal, 16S, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P

Published
2021

3. Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome.

Author

Witt, Suzanne, Bednarska, Olga, Keita, Åsa, Icenhour, Adriane, Jones, Michael, Elsenbruch, Sigrid, Söderholm, Johan, Engström, Maria, Mayer, Emeran, and Walter, Susanna

Subjects
Brain-gut interactions, Coping skills, Default mode network, Gut epithelial permeability, Irritable bowel syndrome, Resting state fMRI, Adult, Brain, Female, Humans, Irritable Bowel Syndrome, Magnetic Resonance Imaging, Middle Aged, Pain, Permeability, Visceral Pain, Young Adult
Abstract

Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

Published
2019

4. Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients

Author

Garcia-Etxebarria, Koldo, Zheng, Tenghao, Bonfiglio, Ferdinando, Bujanda, Luis, Dlugosz, Aldona, Lindberg, Greger, Schmidt, Peter T, Karling, Pontus, Ohlsson, Bodil, Simren, Magnus, Walter, Susanna, Nardone, Gerardo, Cuomo, Rosario, Usai-Satta, Paolo, Galeazzi, Francesca, Neri, Matteo, Portincasa, Piero, Bellini, Massimo, Barbara, Giovanni, Jonkers, Daisy, Eswaran, Shanti, Chey, William D, Kashyap, Purna, Chang, Lin, Mayer, Emeran A, Wouters, Mira M, Boeckxstaens, Guy, Camilleri, Michael, Franke, Andre, and D’Amato, Mauro

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Chronic Pain, Digestive Diseases, Genetics, Pain Research, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Gene Frequency, Genotype, Humans, Irritable Bowel Syndrome, Prevalence, Sucrase-Isomaltase Complex, Gastroenterology & Hepatology, Clinical sciences
Abstract

Patients with irritable bowel syndrome (IBS) often associate their symptoms to certain foods. In congenital sucrase-isomaltase deficiency (CSID), recessive mutations in the SI gene (coding for the disaccharidase digesting sucrose and 60% of dietary starch)1 cause clinical features of IBS through colonic accumulation of undigested carbohydrates, triggering bowel symptoms.2 Hence, in a previous study,3 we hypothesized that CSID variants reducing SI enzymatic activity may contribute to development of IBS symptoms. We detected association with increased risk of IBS for 4 rare loss-of-function variants typically found in (homozygous) CSID patients, because carriers (heterozygous) of these rare variants were more common in patients than in controls.1,4 Through a 2-step computational and experimental strategy, the present study aimed to determine whether other (dys-)functional SI variants are associated with risk of IBS in addition to known CSID mutations. We first aimed to identify all SI rare pathogenic variants (SI-RPVs) on the basis of integrated Mendelian Clinically Applicable Pathogenicity (M-CAP) and Combined Annotation Dependent Depletion (CADD) predictive (clinically relevant) scores; next, we inspected genotype data currently available for 2207 IBS patients from a large ongoing project to compare SI-RPV case frequencies with ethnically matched population frequencies from the Exome Aggregation Consortium (ExAC).

Published
2018

9. Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome

Author

Bonfiglio, Ferdinando, Zheng, Tenghao, Garcia-Etxebarria, Koldo, Hadizadeh, Fatemeh, Bujanda, Luis, Bresso, Francesca, Agreus, Lars, Andreasson, Anna, Dlugosz, Aldona, Lindberg, Greger, Schmidt, Peter T, Karling, Pontus, Ohlsson, Bodil, Simren, Magnus, Walter, Susanna, Nardone, Gerardo, Cuomo, Rosario, Usai-Satta, Paolo, Galeazzi, Francesca, Neri, Matteo, Portincasa, Piero, Bellini, Massimo, Barbara, Giovanni, Latiano, Anna, Hübenthal, Matthias, Thijs, Vincent, Netea, Mihai G, Jonkers, Daisy, Chang, Lin, Mayer, Emeran A, Wouters, Mira M, Boeckxstaens, Guy, Camilleri, Michael, Franke, Andre, Zhernakova, Alexandra, and D'Amato, Mauro

Subjects
Genetics, Prevention, Digestive Diseases, Pain Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Chromosomes, Human, Pair 9, Constipation, Europe, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Irritable Bowel Syndrome, Male, Menarche, Middle Aged, Polymorphism, Single Nucleotide, Self Report, Sex Factors, Sweden, United States, SNP, Biobank Research, Bowel Symptoms, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Background & aimsGenetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants.MethodsWe studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations.ResultsWe identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 × 10-8) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0×10-6). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 × 10-10 in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKBKAP), which is mutated in patients with familial dysautonomia.ConclusionsIn a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

Published
2018

11. Visual Analysis for Understanding Irritable Bowel Syndrome

Author

Jönsson, Daniel, Bergström, Albin, Algström, Isac, Simon, Rozalyn, Engström, Maria, Walter, Susanna, Hotz, Ingrid, COHEN, IRUN R., Editorial Board Member, LAJTHA, ABEL, Editorial Board Member, LAMBRIS, JOHN D., Editorial Board Member, PAOLETTI, RODOLFO, Editorial Board Member, REZAEI, NIMA, Editorial Board Member, and Rea, Paul M., editor

Published
2019
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15. Defecation symptoms in primary health care patients with irritable bowel syndrome.

Author

Sjödahl, Jenny, Ingemansson, Anna, Bureychak, Tetyana, Norlin, Anna-Karin, Jones, Michael P., Faresjö, Åshild, and Walter, Susanna

Subjects
PRIMARY health care, DEFECATION, IRRITABLE colon, PATIENT experience, PATIENT care, QUALITY of life
Abstract

The objectives of the present study were to (a) measure the prevalence of defecation symptoms in IBS, (b) investigate the relationship between stool consistency and defecation symptoms in IBS, and (c) investigate the association of defecation symptoms with health-related quality of life (HRQL) and self-reported stress in patients with IBS cared for in a primary health care setting. Ten primary health care centres joined the study. 282 patients with IBS as well as 372 non-IBS controls filled in gastrointestinal symptom diaries prospectively for two weeks as well as the Perceived Stress Scale-14 (PSS14) and the EuroQol barometer to measure perceived stress and HRQL, respectively. Incomplete evacuation was present in 51% vs. 21% of the stools among the IBS patients and the non-IBS controls, respectively. The need to strain during defecation was existing in 41% vs. 33% of the stools for the IBS patients and the non-IBS controls, respectively. Urgency was experienced in 37% of the stools in the IBS patients compared with 18% of the stools in the non-IBS controls. Patients with IBS experienced in a significant higher degree of overlapping symptoms per stool (p < 0.001 to p = 0.007). The occurrence of all defecation symptoms in the same patient was related to decreased HRQL, and increased stress (p = 0.001 to p < 0.001). An overlap between IBS and symptoms from the anorectal region related to defecation was found in a primary health care population. Defecation symptoms are very common in primary care IBS-patients, it co-occurs with increased self-perceived stress, and decreased HRQL. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Author

Eijsbouts, Chris, Zheng, Tenghao, Kennedy, Nicholas A., Bonfiglio, Ferdinando, Anderson, Carl A., Moutsianas, Loukas, Holliday, Joanne, Shi, Jingchunzi, Shringarpure, Suyash, Voda, Alexandru-Ioan, Farrugia, Gianrico, Franke, Andre, H��benthal, Matthias, Abecasis, Gon��alo, Zawistowski, Matthew, Skogholt, Anne Heidi, Ness-Jensen, Eivind, Hveem, Kristian, Esko, T��nu, Teder-Laving, Maris, Zhernakova, Alexandra, Camilleri, Michael, Boeckxstaens, Guy, Whorwell, Peter J., Spiller, Robin, McVean, Gil, D���Amato, Mauro, Jostins, Luke, Parkes, Miles, Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Clark, Sarah K., Elson, Sarah L., Fletez-Brant, Kipper, Fontanillas, Pierre, Furlotte, Nicholas A., Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K., Luff, Marie K., McCreight, Jey C., McIntyre, Matthew H., McManus, Kimberly F., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., Northover, Carrie A. M., O���Connell, Jared, Petrakovitz, Aaron A., Pitts, Steven J., Poznik, G. David, Sathirapongsasuti, J. Fah, Shastri, Anjali J., Shelton, Janie F., Tian, Chao, Tung, Joyce Y., Tunney, Robert J., Vacic, Vladimir, Wang, Xin, Zare, Amir S., Kashyap, Purna, Chang, Lin, Mayer, Emeran, Heitkemper, Margaret, Sayuk, Gregory S., Ringel-Kulka, Tamar, Ringel, Yehuda, Chey, William D., Eswaran, Shanti, Merchant, Juanita L., Shulman, Robert J., Bujanda, Luis, Garcia-Etxebarria, Koldo, Dlugosz, Aldona, Lindberg, Greger, Schmidt, Peter T., Karling, Pontus, Ohlsson, Bodil, Walter, Susanna, Faresj��, ��shild O., Simren, Magnus, Halfvarson, Jonas, Portincasa, Piero, Barbara, Giovanni, Usai-Satta, Paolo, Neri, Matteo, Nardone, Gerardo, Cuomo, Rosario, Galeazzi, Francesca, Bellini, Massimo, Latiano, Anna, Houghton, Lesley, Jonkers, Daisy, Kurilshikov, Alexander, Weersma, Rinse K., Netea, Mihai, Tesarz, Jonas, Gauss, Annika, Goebel-Stengel, Miriam, Andresen, Viola, Frieling, Thomas, Pehl, Christian, Schaefert, Rainer, Niesler, Beate, Lieb, Wolfgang, Hanevik, Kurt, Langeland, Nina, Wensaas, Knut-Arne, Litleskare, Sverre, Gabrielsen, Maiken E., Thomas, Laurent, Thijs, Vincent, Lemmens, Robin, Van Oudenhove, Lukas, Wouters, Mira, Eijsbouts C., Zheng T., Kennedy N.A., Bonfiglio F., Anderson C.A., Moutsianas L., Holliday J., Shi J., Shringarpure S., Agee M., Aslibekyan S., Auton A., Bell R.K., Bryc K., Clark S.K., Elson S.L., Fletez-Brant K., Fontanillas P., Furlotte N.A., Gandhi P.M., Heilbron K., Hicks B., Hinds D.A., Huber K.E., Jewett E.M., Jiang Y., Kleinman A., Lin K.-H., Litterman N.K., Luff M.K., McCreight J.C., McIntyre M.H., McManus K.F., Mountain J.L., Mozaffari S.V., Nandakumar P., Noblin E.S., Northover C.A.M., O'Connell J., Petrakovitz A.A., Pitts S.J., Poznik G.D., Sathirapongsasuti J.F., Shastri A.J., Shelton J.F., Tian C., Tung J.Y., Tunney R.J., Vacic V., Wang X., Zare A.S., Voda A.-I., Kashyap P., Chang L., Mayer E., Heitkemper M., Sayuk G.S., Ringel-Kulka T., Ringel Y., Chey W.D., Eswaran S., Merchant J.L., Shulman R.J., Bujanda L., Garcia-Etxebarria K., Dlugosz A., Lindberg G., Schmidt P.T., Karling P., Ohlsson B., Walter S., Faresjo A.O., Simren M., Halfvarson J., Portincasa P., Barbara G., Usai-Satta P., Neri M., Nardone G., Cuomo R., Galeazzi F., Bellini M., Latiano A., Houghton L., Jonkers D., Kurilshikov A., Weersma R.K., Netea M., Tesarz J., Gauss A., Goebel-Stengel M., Andresen V., Frieling T., Pehl C., Schaefert R., Niesler B., Lieb W., Hanevik K., Langeland N., Wensaas K.-A., Litleskare S., Gabrielsen M.E., Thomas L., Thijs V., Lemmens R., Van Oudenhove L., Wouters M., Farrugia G., Franke A., Hubenthal M., Abecasis G., Zawistowski M., Skogholt A.H., Ness-Jensen E., Hveem K., Esko T., Teder-Laving M., Zhernakova A., Camilleri M., Boeckxstaens G., Whorwell P.J., Spiller R., McVean G., D'Amato M., Jostins L., Parkes M., Eijsbouts, Chris [0000-0001-5179-0653], Anderson, Carl A. [0000-0003-1719-7009], Moutsianas, Loukas [0000-0001-5453-345X], Holliday, Joanne [0000-0003-4568-7320], Shringarpure, Suyash [0000-0001-6464-2668], Voda, Alexandru-Ioan [0000-0003-2974-6992], Farrugia, Gianrico [0000-0003-3473-5235], Hübenthal, Matthias [0000-0002-5956-3006], Abecasis, Gonçalo [0000-0003-1509-1825], Zawistowski, Matthew [0000-0002-3005-083X], Ness-Jensen, Eivind [0000-0001-6005-0729], Teder-Laving, Maris [0000-0002-5872-1850], Camilleri, Michael [0000-0001-6472-7514], Whorwell, Peter J. [0000-0002-5220-8474], Spiller, Robin [0000-0001-6371-4500], McVean, Gil [0000-0002-5012-4162], D’Amato, Mauro [0000-0003-2743-5197], Jostins, Luke [0000-0002-2475-3969], Parkes, Miles [0000-0002-6467-0631], Apollo - University of Cambridge Repository, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Eijsbouts, C., Zheng, T., Kennedy, N. A., Bonfiglio, F., Anderson, C. A., Moutsianas, L., Holliday, J., Shi, J., Shringarpure, S., Agee, M., Aslibekyan, S., Auton, A., Bell, R. K., Bryc, K., Clark, S. K., Elson, S. L., Fletez-Brant, K., Fontanillas, P., Furlotte, N. A., Gandhi, P. M., Heilbron, K., Hicks, B., Hinds, D. A., Huber, K. E., Jewett, E. M., Jiang, Y., Kleinman, A., Lin, K. -H., Litterman, N. K., Luff, M. K., Mccreight, J. C., Mcintyre, M. H., Mcmanus, K. F., Mountain, J. L., Mozaffari, S. V., Nandakumar, P., Noblin, E. S., Northover, C. A. M., O'Connell, J., Petrakovitz, A. A., Pitts, S. J., Poznik, G. D., Sathirapongsasuti, J. F., Shastri, A. J., Shelton, J. F., Tian, C., Tung, J. Y., Tunney, R. J., Vacic, V., Wang, X., Zare, A. S., Voda, A. -I., Kashyap, P., Chang, L., Mayer, E., Heitkemper, M., Sayuk, G. S., Ringel-Kulka, T., Ringel, Y., Chey, W. D., Eswaran, S., Merchant, J. L., Shulman, R. J., Bujanda, L., Garcia-Etxebarria, K., Dlugosz, A., Lindberg, G., Schmidt, P. T., Karling, P., Ohlsson, B., Walter, S., Faresjo, A. O., Simren, M., Halfvarson, J., Portincasa, P., Barbara, G., Usai-Satta, P., Neri, M., Nardone, G., Cuomo, R., Galeazzi, F., Bellini, M., Latiano, A., Houghton, L., Jonkers, D., Kurilshikov, A., Weersma, R. K., Netea, M., Tesarz, J., Gauss, A., Goebel-Stengel, M., Andresen, V., Frieling, T., Pehl, C., Schaefert, R., Niesler, B., Lieb, W., Hanevik, K., Langeland, N., Wensaas, K. -A., Litleskare, S., Gabrielsen, M. E., Thomas, L., Thijs, V., Lemmens, R., Van Oudenhove, L., Wouters, M., Farrugia, G., Franke, A., Hubenthal, M., Abecasis, G., Zawistowski, M., Skogholt, A. H., Ness-Jensen, E., Hveem, K., Esko, T., Teder-Laving, M., Zhernakova, A., Camilleri, M., Boeckxstaens, G., Whorwell, P. J., Spiller, R., Mcvean, G., D'Amato, M., Jostins, L., and Parkes, M.

Subjects
Male, Molecular Chaperone, Mood Disorder, 631/208/205/2138, Biology, 692/699/1503/1502/2071, Bioinformatics, Polymorphism, Single Nucleotide, Genetic pathways, 38/43, Irritable Bowel Syndrome, Cytoskeletal Protein, Genetics, medicine, Genetic predisposition, Aged, Anxiety Disorders, CD56 Antigen, Cell Adhesion Molecules, Cytoskeletal Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Guanine Nucleotide Exchange Factors, Homeodomain Proteins, Humans, Middle Aged, Molecular Chaperones, Mood Disorders, United Kingdom, Polymorphism, 692/699/476, Irritable bowel syndrome, Depression (differential diagnoses), article, Homeodomain Protein, Single Nucleotide, Guanine Nucleotide Exchange Factor, medicine.disease, Neuroticism, Biobank, Mood, Cell Adhesion Molecule, Anxiety, medicine.symptom, Anxiety Disorder, Human
Abstract

Funder: Kennedy Trust Rheumatology Research Prize Studentship, Funder: DFG Cluster of Excellence ���Precision Medicine in Chronic In-flammation��� (PMI; ID: EXC2167), Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: ���Ideas��� Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772, Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL, Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421, Irritable bowel syndrome (IBS) results from disordered brain���gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain���gut interactions underlying IBS.

Published
2021

26. Functional variants in the sucrase–isomaltase gene associate with increased risk of irritable bowel syndrome

Author

Henström, Maria, Diekmann, Lena, Bonfiglio, Ferdinando, Hadizadeh, Fatemeh, Kuech, Eva-Maria, von Köckritz-Blickwede, Maren, Thingholm, Louise B, Zheng, Tenghao, Assadi, Ghazaleh, Dierks, Claudia, Heine, Martin, Philipp, Ute, Distl, Ottmar, Money, Mary E, Belheouane, Meriem, Heinsen, Femke-Anouska, Rafter, Joseph, Nardone, Gerardo, Cuomo, Rosario, Usai-Satta, Paolo, Galeazzi, Francesca, Neri, Matteo, Walter, Susanna, Simrén, Magnus, Karling, Pontus, Ohlsson, Bodil, Schmidt, Peter T, Lindberg, Greger, Dlugosz, Aldona, Agreus, Lars, Andreasson, Anna, Mayer, Emeran, Baines, John F, Engstrand, Lars, Portincasa, Piero, Bellini, Massimo, Stanghellini, Vincenzo, Barbara, Giovanni, Chang, Lin, Camilleri, Michael, Franke, Andre, Naim, Hassan Y, and DʼAmato, Mauro

Published
2018
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27. TRPM8 polymorphisms associated with increased risk of IBS-C and IBS-M

Author

Henström, Maria, Hadizadeh, Fatemeh, Beyder, Arthur, Bonfiglio, Ferdinando, Zheng, Tenghao, Assadi, Ghazaleh, Rafter, Joseph, Bujanda, Luis, Agreus, Lars, Andreasson, Anna, Dlugosz, Aldona, Lindberg, Greger, Schmidt, Peter T, Karling, Pontus, Ohlsson, Bodil, Talley, Nicholas J, Simren, Magnus, Walter, Susanna, Wouters, Mira, Farrugia, Gianrico, and DʼAmato, Mauro

Published
2017
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31. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome

Author

Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A., Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A., Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, and D’Amato, Mauro

Published
2021
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32. Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts

Author

Ek, Weronica E, Reznichenko, Anna, Ripke, Stephan, Niesler, Beate, Zucchelli, Marco, Rivera, Natalia V, Schmidt, Peter T, Pedersen, Nancy L, Magnusson, Patrik, Talley, Nicholas J, Holliday, Elizabeth G, Houghton, Lesley, Gazouli, Maria, Karamanolis, George, Rappold, Gudrun, Burwinkel, Barbara, Surowy, Harald, Rafter, Joseph, Assadi, Ghazaleh, Li, Ling, Papadaki, Evangelia, Gambaccini, Dario, Marchi, Santino, Colucci, Rocchina, Blandizzi, Corrado, Barbaro, Raffaella, Karling, Pontus, Walter, Susanna, Ohlsson, Bodil, Tornblom, Hans, Bresso, Francesca, Andreasson, Anna, Dlugosz, Aldona, Simren, Magnus, Agreus, Lars, Lindberg, Greger, Boeckxstaens, Guy, Bellini, Massimo, Stanghellini, Vincenzo, Barbara, Giovanni, Daly, Mark J, Camilleri, Michael, Wouters, Mira M, and DʼAmato, Mauro

Published
2015
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34. Acute psychological stress increases paracellular permeability and modulates immune activity in rectal mucosa of healthy volunteers

Author

Gerdin, Linda, González‐Castro, Ana M., Ericson, Ann‐Charlott, Persborn, Mats, Santos, Javier, Walter, Susanna A., Keita, Åsa V., Vicario, Maria, and Söderholm, Johan D.

Abstract

Psychological stress and increased permeability are implicated as contributing factors in the initiation and worsening of gastrointestinal diseases. A link between stress and intestinal permeability has been shown in animal models as well as in human small intestine, but stress effects on the human colorectal mucosal barrier has not been reported. To investigate the potential effects of acute psychological stress on colorectal mucosal barrier function and to explore stress‐induced molecular events in the rectal mucosa under healthy conditions. Endoscopic biopsies were taken from the rectosigmoid region of healthy volunteers, who had been subjected to dichotomous listening stress and after a control session, respectively. Paracellular and transcellular permeability were assessed in modified Ussing chambers. RNA expression (microarray technology confirmed by quantitative real‐time polymerase chain reaction) and biological pathway analysis were used to investigate the local mucosal response to acute stress. Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability. We also identified a stress‐induced reduction in RNA expression of genes related to immune cell activation and maturation (CR2, CD20, TCLA1, BANK1, CD22, FDCSP), signaling molecules of homing of immune cells to the gut (chemokines: CCL21, CXCL13, and CCL19, and receptors: CCR7, CXCR5), and innate immunity (DUOX2). Eight of the 10 top down‐regulated genes are directly involved in B cell activation, signaling and migration. The systemic stress response correlated positively with paracellular permeability and negatively with DUOX2expression. Dichotomous listening stress increases paracellular permeability and modulates immune cell activity in the rectal mucosa. Further studies are warranted to identify the primary mechanisms of stress‐mediated reduction of mucosal defensive activity and barrier dysfunction, and their potential implications for gastrointestinal disorders.

Published
2023
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35. Gastrointestinal symptoms - an illness burden that affects daily work in patients with IBS

Author

Olsen Faresjö, Åshild, Walter, Susanna, Norlin, Anna-Karin, Faresjö, Tomas, and Jones, Michael P.

Subjects
Hälso- och sjukvårdsorganisation, hälsopolitik och hälsoekonomi, Adult, Employment, Male, Efficiency, lcsh:Computer applications to medicine. Medical informatics, Irritable Bowel Syndrome, Cost of Illness, Surveys and Questionnaires, IBS, Adaptation, Psychological, Humans, Confidence in public health, Sweden, Research, Health Care Service and Management, Health Policy and Services and Health Economy, Disease burden, Middle Aged, Abdominal Pain, Case-Control Studies, Sense of coherence, Quality of Life, lcsh:R858-859.7, Female, Attitude to Health
Abstract

BackgroundIrritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder characterised by recurrent abdominal pain and disturbed bowel habits and unclear aetiology. IBS is also associated with psychosocial factors, impaired quality of life and lost work productivity. This study sought to determine whether the association between IBS and lost work productivity might be accounted for by poor coping strategies and loss of confidence in the healthcare system.MethodsCase-control design was employed sampling IBS and non-gastrointestinal (non-GI) primary healthcare seekers in a defined region in Sweden. Non-GI patients were of similar age and sex distribution to the IBS patients. Questionnaires applied in this study included instruments designed to measure confidence in the social security system and in the community, as well as questions about whether gastrointestinal problems might affect working life and Sense of coherence (SOC) questionnaire. The studys primary hypothesis was evaluated via an a priori path model.ResultsStatistically significant differences were found between IBS cases (n=305) and controls (n=369) concerning abdominal pain or discomfort affecting everyday performance at work (pamp;lt;0.0001). IBS cases also showed significantly lower (p=0.001) confidence in public healthcare. The studys hypothesis was supported with the finding of a statistically significant indirect association via poor coping strategies, although the indirect associations were lesser in magnitude than the direct association.ConclusionsThis study found a clear association between clinically diagnosed IBS status and interference in work by gastrointestinal symptoms in which sense of coherence might be of importance. Funding Agencies|FORSS - the Research Council of Southeast Sweden

Published
2019

36. Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS—A possible association with microbiota?

Author

Casado-Bedmar, Maite, primary, de-Faria, Felipe Meira, additional, Biskou, Olga, additional, Lindqvist, Carl Mårten, additional, Ranasinghe, Purnika Damindi, additional, Bednarska, Olga, additional, Peterson, Christer, additional, Walter, Susanna A, additional, Carlson, Marie, additional, and Keita, Åsa V, additional

Published
2021
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41. Elevated F‐EDN correlates with mucosal eosinophil degranulation in patients with IBS—A possible association with microbiota?

Author

Casado‐Bedmar, Maite, de‐Faria, Felipe Meira, Biskou, Olga, Lindqvist, Carl Mårten, Ranasinghe, Purnika Damindi, Bednarska, Olga, Peterson, Christer, Walter, Susanna A., Carlson, Marie, and Keita, Åsa V.

Subjects
EOSINOPHILS, IRRITABLE colon, BASIC proteins, YERSINIA enterocolitica, SALMONELLA typhimurium
Abstract

Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil‐derived neurotoxin (F‐EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F‐EDN and microbiota analysis. Differentiated 15HL‐60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o‐phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F‐EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL‐60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F‐EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota. [ABSTRACT FROM AUTHOR]

Published
2022
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42. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author

Kurilshikov, Alexander, primary, Medina-Gomez, Carolina, additional, Bacigalupe, Rodrigo, additional, Radjabzadeh, Djawad, additional, Wang, Jun, additional, Demirkan, Ayse, additional, Roy, Caroline I. Le, additional, Raygoza Garay, Juan Antonio, additional, Finnicum, Casey T., additional, Liu, Xingrong, additional, Zhernakova, Daria V., additional, Bonder, Marc Jan, additional, Hansen, Tue H., additional, Frost, Fabian, additional, Rühlemann, Malte C., additional, Turpin, Williams, additional, Moon, Jee-Young, additional, Kim, Han-Na, additional, Lüll, Kreete, additional, Barkan, Elad, additional, Shah, Shiraz A., additional, Fornage, Myriam, additional, Szopinska-Tokov, Joanna, additional, Wallen, Zachary D., additional, Borisevich, Dmitrii, additional, Agreus, Lars, additional, Andreasson, Anna, additional, Bang, Corinna, additional, Bedrani, Larbi, additional, Bell, Jordana T., additional, Bisgaard, Hans, additional, Boehnke, Michael, additional, Boomsma, Dorret I., additional, Burk, Robert D., additional, Claringbould, Annique, additional, Croitoru, Kenneth, additional, Davies, Gareth E., additional, van Duijn, Cornelia M., additional, Duijts, Liesbeth, additional, Falony, Gwen, additional, Fu, Jingyuan, additional, van der Graaf, Adriaan, additional, Hansen, Torben, additional, Homuth, Georg, additional, Hughes, David A., additional, Ijzerman, Richard G., additional, Jackson, Matthew A., additional, Jaddoe, Vincent W.V., additional, Joossens, Marie, additional, Jørgensen, Torben, additional, Keszthelyi, Daniel, additional, Knight, Rob, additional, Laakso, Markku, additional, Laudes, Matthias, additional, Launer, Lenore J., additional, Lieb, Wolfgang, additional, Lusis, Aldons J., additional, Masclee, Ad A.M., additional, Moll, Henriette A., additional, Mujagic, Zlatan, additional, Qibin, Qi, additional, Rothschild, Daphna, additional, Shin, Hocheol, additional, Sørensen, Søren J., additional, Steves, Claire J., additional, Thorsen, Jonathan, additional, Timpson, Nicholas J., additional, Tito, Raul Y., additional, Vieira-Silva, Sara, additional, Völker, Uwe, additional, Völzke, Henry, additional, Võsa, Urmo, additional, Wade, Kaitlin H., additional, Walter, Susanna, additional, Watanabe, Kyoko, additional, Weiss, Stefan, additional, Weiss, Frank U., additional, Weissbrod, Omer, additional, Westra, Harm-Jan, additional, Willemsen, Gonneke, additional, Payami, Haydeh, additional, Jonkers, Daisy M.A.E., additional, Vasquez, Alejandro Arias, additional, de Geus, Eco J.C., additional, Meyer, Katie A., additional, Stokholm, Jakob, additional, Segal, Eran, additional, Org, Elin, additional, Wijmenga, Cisca, additional, Kim, Hyung-Lae, additional, Kaplan, Robert C., additional, Spector, Tim D., additional, Uitterlinden, Andre G., additional, Rivadeneira, Fernando, additional, Franke, Andre, additional, Lerch, Markus M., additional, Franke, Lude, additional, Sanna, Serena, additional, D’Amato, Mauro, additional, Pedersen, Oluf, additional, Paterson, Andrew D., additional, Kraaij, Robert, additional, Raes, Jeroen, additional, and Zhernakova, Alexandra, additional

Published
2020
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44. GWAS of stool frequency reveals genes, pathways, and cell types relevant to human gastrointestinal motility and irritable bowel syndrome

Author

Bonfiglio, Ferdinando, primary, Liu, Xingrong, additional, Smillie, Christopher, additional, Pandit, Anita, additional, Kurilshikov, Alexander, additional, Bacigalupe, Rodrigo, additional, Zheng, Tenghao, additional, Nim, Hieu, additional, Garcia-Etxebarria, Koldo, additional, Bujanda, Luis, additional, Andreasson, Anna, additional, Agreus, Lars, additional, Walter, Susanna, additional, Abecasis, Goncalo, additional, Eijsbouts, Chris, additional, Jostins, Luke, additional, Parkes, Miles, additional, Hughes, David A, additional, Timpson, Nicholas, additional, Raes, Jeroen, additional, Franke, Andre, additional, Kennedy, Nicholas A, additional, Regev, Aviv, additional, Zhernakova, Alexandra, additional, Simren, Magnus, additional, Camilleri, Michael, additional, and D’Amato, Mauro, additional

Published
2020
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45. Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome

Author

Witt, Suzanne Tyson, Bednarska, Olga, Keita, Åsa, Icenhour, Adriane, Jones, Michael P., Elsenbruch, Sigrid, Söderholm, Johan D, Engström, Maria, Mayer, Emeran A., and Walter, Susanna

Subjects
digestive, oral, and skin physiology, Neurosciences, Medizin, lcsh:R858-859.7, Irritable bowel syndrome, Gut epithelial permeability, Resting state fMRI, Brain-gut interactions, Default mode network, Coping skills, lcsh:Computer applications to medicine. Medical informatics, Neurovetenskaper, lcsh:Neurology. Diseases of the nervous system, lcsh:RC346-429
Abstract

Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions. Funding Agencies|AFA FOrskning [AFA140417]; County Council of Ostergotland [SLS-693541, SLS-503411]; Region Ostergotland [LIO-700871, LIO-606201, LIO-536281, LIO-514271]; Deutsche Forschungsgemeinschaft [DFG IC 81/1-1]; Bengt-Ihre Fonden

Published
2019

49. Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome

Author

Icenhour, Adriane, Witt, Suzanne T., Elsenbruch-Harnish, Sigrid, Lowén, Mats, Engström, Maria, Tillisch, Kirsten, Mayer, Emeran A., and Walter, Susanna

Subjects
Adult, Male, Medizin, Brain, Regular Article, Visceral Pain, lcsh:Computer applications to medicine. Medical informatics, Magnetic Resonance Imaging, lcsh:RC346-429, Irritable Bowel Syndrome, Functional connectivity, Salience network, Default mode network, lcsh:R858-859.7, Humans, Female, Resting-state fMRI, Nerve Net, Sensorimotor network, lcsh:Neurology. Diseases of the nervous system, Pain Measurement, Visceral hypersensitivity
Abstract

Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N = 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS., Graphical abstract Image 1, Highlights • Functional connectivity (FC) was compared between hyper- and normosensitive IBS. • Hypersensitive IBS showed enhanced salience and sensorimotor network FC. • Normosensitive IBS had decreased amygdala and anterior insula FC within the DMN. • Changes in FC were associated with visceral sensitivity and symptom severity. • Altered FC may play a key role in hypervigilance and hyperalgesia in IBS.

Published
2017

50. Letter: A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency in GUT, vol 66, issue 4, pp 756-758

Author

Jankipersadsing, Soesma A., Hadizadeh, Fatemeh, Jan Bonder, Marc, Tigchelaar, Ettje F., Deelen, Patrick, Fu, Jingyuan, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Wijmenga, Cisca, Hysi, Pirro, DAmato, Mauro, and Zhernakova, Alexandra

Subjects
Klinisk medicin, Clinical Medicine
Abstract

n/a Funding Agencies|Top Institute Food and Nutrition, Wageningen [GH001]; Netherlands Organization for Scientific Research [NWO-VIDI 864.13.013]; Swedish Research Council (VR); University of Groningen

Published
2017

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