Gastrointestinal epidemiology – Jonas Ludvigsson's research group

We study causes and consequences of gastrointestinal diseases (including the liver, gallbladder and pancreas). We do so through linking histopathology data with the Swedish national healthcare registers.

Part of the Department of Medical Epidemiology and Biostatistics
Jonas Ludvigsson's research group

The gastrointestinal (GI) epidemiology group focus on research on GI organs and diseases. Most of that research is based on the ESPRESSO study, which you can read more about on a separate tab on this page. Through histopathology data we are able to examine a range conditions, including cancer precursors, the brain-gut axis, disease phenotypes, etc. Our research has been published in journals such as the New Engl J Medicine, Lancet, JAMA, the BMJ, Annals of Internal Medicine, Gastroenterology and Gut.

Publications

All publications from group members

Staff and contact

Group leader

All members of the group

Other people connected to the group

  • Yuan, Shuai

Visiting address

Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Nobels väg 12A, Stockholm, 171 77, Sweden

Postal address

Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, PO Box 281, Stockholm, 171 77, Sweden

ESPRESSO

A cup of smoking hot espresso
Photo: Pavel Koubek, Icon Photography

Between 2015-17, all pathology departments (n=28) in Sweden were contacted to obtain histopathology record data from the GI tract (pharynx to anus), liver, gallbladder and pancreas. For each individual, local histopathology IT personnel retrieved data on personal identity number, date of histopathology, topography (where the biopsy was taken), morphology (biopsy appearance), and where available free text. In total, histopathology record data were available in 2.1 million individuals between 1965 and 2017, but the number of data entries (since many individuals had been biopsied more than once) was 6.1 million. A subset of records also contain the free text from the histopathology report. Index individuals with histopathology data have since been matched with up to five controls from the general population, and all first-degree relatives and spouses have been identified. In total, the study population consists of 13.0 million individuals. In 2021-2023, we collected new histopathology data from Sweden’s 28 pathology department. An updated version of ESPRESSO is expected in early 2024. We expect the new cohort to be 25% bigger than the current one (covering the years up until 2017).

Data from all study participants have been linked to Swedish National Healthcare Registers allowing research on such aspects as fetal and perinatal conditions and risk of future GI disease, but also risk of comorbidity, complications (including cancer) and death in GI disease. Furthermore, the ESPRESSO study enables researchers to identify diagnoses and disease phenotypes that are not currently indexed in national registers (including disease precursors), but also to increase sensitivity and specificity of already recorded diseases in the National Health Registers.

Combining topography and morphology codes allows researchers to identify specific diseases. ESPRESSO can also be used to identify unspecific findings in a particular location (for instance 893,117 unique individuals have a colorectal histopathology report; 179,110 have a liver histopathology report, and the database contains 492,413 unique individuals with a normal small intestinal mucosa).

If you wish to donate to our research, you are welcome to send your contribution by Swish to 123 202 32 08. Mark your donation with ESPRESSO. For larger donations (over 10,000 SEK) please contact KI Development Office.

Study personnel

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Jonas Ludvigsson

Professor
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David Bergman

Postdoctoral Researcher

Fahim Ebrahimi

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Jiangwei Sun

Postdoctoral Researcher
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Jialu Yao

Phd Student
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Bjorn Roelstraete

Affiliated to Research
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Mariam Lashkariani

System Developer
+46852482316
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Linn Austin

Administrator
+46852482417

Collaborators

Hamed Khalili

Collaborator

Associate Professor at Harvard Medical School and Crohn’s and Colitis Center, Massachusetts General Hospital

Research interest: As a gastroenterologist, I am dedicated to clinical and translational investigations of inflammatory bowel diseases. To date, my research has focused on understanding and defining environmental predictors, such as diet, reproductive, and lifestyle factors, and their interplay with common genetic risk loci and the gut microbial environment, on risk and progression of inflammatory bowel disorders.

Benjamin Lebwohl

Collaborator

Departments of Medicine and Epidemiology, Celiac Disease Center, Columbia University

I am a gastroenterologist and clinical researcher with a primary focus on celiac disease and gluten-related disorders. I have investigated risk factors, long-term outcomes, and practice patterns in celiac disease. I am also investigating the changing mortality risk in this condition over time. My secondary focus is on colorectal cancer prevention, with an emphasis on colonoscopy quality.

Tracey Simon

Collaborator

Department of Epidemiology, Harvard T.H. Chan School of Public Health

I am examining the association between commonly-used medications (aspirin, statins) and clinical outcomes in patients with biopsy-proven nonalcoholic fatty liver disease.

Kyle Staller

Collaborator

Department of Epidemiology, Harvard T.H. Chan School of Public Health

I am examining the relationship between irritable bowel syndrome (IBS) and outcomes more traditionally associated with non-functional GI disorders such as mortality.

Yin Cao, ScD, MPH

Collaborator

Associate Professor of Surgery and Medicine, Washington University School of Medicine in St Louis

I am a molecular cancer epidemiologist. My lab incorporates high-throughput technologies (genomics, proteomics, microbiome, accelerometers) into large-scale collaborative epidemiologic and clinical studies to identify emerging risk factors and novel biomarkers for early-onset cancers. 

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Anders Forss

Affiliated to Research
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Louise Emilsson

Associate Professor University of Oslo & Docent MEB, KI

PhD students

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Soran Rabin Bozorg

Funding

The ESPRESSO study is supported by:

  • The Swedish Research Council
  • Mag-Tarmfonden (the Gastrointestinal fund)
  • European Crohn's and Colitis Organization
  • Stiftelsen Professor Nanna Svartz Fond
  • The Swedish Society for Medical Research
  • Ruth and Richard Julin Foundation
  • The Swedish Society of Medicine (in general, through the Gastroenterologisk fond and Ihre Fonden). 

Publications

Progression of non-alcoholic fatty liver disease and long-term outcomes: A nationwide paired liver biopsy cohort study.
Simon TG, Roelstraete B, Hagström H, Loomba R, Ludvigsson JF
J Hepatol 2023 Dec;79(6):1366-1373

Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study.
Ebrahimi F, Hagström H, Sun J, Bergman D, Shang Y, Yang W, Roelstraete B, Ludvigsson JF
J Hepatol 2023 Dec;79(6):1374-1384

Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study.
Mårild K, Söderling J, Stephansson O, Axelrad J, Halfvarson J, , Bröms G, Marsal J, Olén O, Ludvigsson JF
Gastroenterology 2024 May;166(5):802-814.e18

Coeliac disease and type 2 diabetes risk: a nationwide matched cohort and Mendelian randomisation study.
Yuan S, Leffler D, Lebwohl B, Green PHR, Sun J, Carlsson S, Larsson SC, Ludvigsson JF
Diabetologia 2024 Aug;67(8):1630-1641

Psychiatric Disorders Among 5,800 Patients With Microscopic Colitis: A Nationwide Population-Based Matched Cohort Study.
Bergman D, Roelstraete B, Sun J, Ebrahimi F, Butwicka A, Pardi DS, Ludvigsson JF
Am J Gastroenterol 2024 Jul;():

Birth Weight, Gestational Age, and Risk of Pediatric-Onset MASLD.
Ebrahimi F, Yao J, Hagström H, Stephansson O, Sun J, Bergman D, Söderling J, Ludvigsson JF
JAMA Netw Open 2024 Sep;7(9):e2432420

Bidirectional association between inflammatory bowel disease and type 1 diabetes: a nationwide matched cohort and case-control study.
Sun J, Yao J, Olén O, Halfvarsson J, Bergman D, Ebrahimi F, Carlsson S, Ludvigsson J, Ludvigsson JF
Lancet Reg Health Eur 2024 Nov;46():101056

Target trial emulation of aspirin after diagnosis of colorectal polyps.
Emilsson L, Song M, Ludvigsson JF
Eur J Epidemiol 2023 Oct;38(10):1105-1114

Risk of Severe Infection in Patients With Biopsy-proven Nonalcoholic Fatty Liver Disease - A Population-based Cohort Study.
Ebrahimi F, Simon TG, Hagström H, Söderling J, Wester A, Roelstraete B, Ludvigsson JF
Clin Gastroenterol Hepatol 2023 Dec;21(13):3346-3355.e19

Pregnancy and neonatal outcomes among women with early-onset colorectal cancer: a nationwide case-control study.
Cao Y, Zhao S, Bexelius TS, Söderling J, Shi M, Roelstraete B, Warner BB, Stephansson O, Ludvigsson JF
EClinicalMedicine 2023 May;59():101963

Pregnancy Outcomes in Women With Autoimmune Hepatitis - A Nationwide Population-based Cohort Study With Histopathology.
Sharma R, Simon TG, Stephansson O, Verna EC, Emond J, Söderling J, Roelstraete B, Hagström H, Ludvigsson JF
Clin Gastroenterol Hepatol 2023 Jan;21(1):103-114.e10

A nationwide cohort study of the incidence of inflammatory bowel disease in Sweden from 1990 to 2014.
Forss A, Clements M, Bergman D, Roelstraete B, Kaplan GG, Myrelid P, Halfvarson J, Olén O, Ludvigsson JF
Aliment Pharmacol Ther 2022 Mar;55(6):691-699

Work Loss in Patients With Celiac Disease: A Population-based Longitudinal Study.
Bozorg SR, Söderling J, Everhov ÅH, Lebwohl B, Green PHR, Neovius M, Ludvigsson JF, Mårild K
Clin Gastroenterol Hepatol 2022 May;20(5):1068-1076.e6

Maternal obesity increases the risk and severity of NAFLD in offspring.
Hagström H, Simon TG, Roelstraete B, Stephansson O, Söderling J, Ludvigsson JF
J Hepatol 2021 11;75(5):1042-1048

Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality.
Simon TG, Roelstraete B, Hartjes K, Shah U, Khalili H, Arnell H, Ludvigsson JF
J Hepatol 2021 11;75(5):1034-1041

Two waves of coeliac disease incidence in Sweden: a nationwide population-based cohort study from 1990 to 2015.
Bergman D, King J, Lebwohl B, Clements MS, Roelstraete B, Kaplan GG, Green PH, Murray JA, Ludvigsson JF
Gut 2022 Jun;71(6):1088-1094

Gastrointestinal Infection and Risk of Microscopic Colitis: A Nationwide Case-Control Study in Sweden.
Khalili H, Axelrad JE, Roelstraete B, Olén O, D'Amato M, Ludvigsson JF
Gastroenterology 2021 04;160(5):1599-1607.e5

Risk of colorectal cancer in first degree relatives of patients with colorectal polyps: nationwide case-control study in Sweden.
Song M, Emilsson L, Roelstraete B, Ludvigsson JF
BMJ 2021 05;373():n877

Cohort profile: ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden).
Ludvigsson JF, Lashkariani M
Clin Epidemiol 2019 ;11():101-114

Please go to "documents" for the pdf version of the publication.

Documents

IBD Alliance

Inflammatory bowel disease (IBD) affects about 1% of the Swedish population. It is generally divided into ulcerative colitis (UC), Crohn’s disease (CD), and unspecified IBD (IBD-U). IBD has undergone major changes over time. While the mortality in the 1950s was 30-40%, new treatment has meant that death is now rare in IBD. Initial treatment was restricted to bowel surgery (especially colectomy), until steroids were introduced and later 5-ASA and thiopurines. Today, IBD is one of the most exciting areas for new treatments. TNF-blockers and other biologics have shown great effect. Also the interplay between microbiota and dietary intake yields promises (the NOD2 mutation plays an important role in Crohn’s disease and recognises bacterial peptides). In children enteral nutrition often has a substantial effect on disease activity, and fecal transplantation is a potential treatment.

The increased survival in IBD means that physicians more and more will have to focus on long-term complications such as colorectal cancer, lymphoma and opportunistic infections. Patients are followed by regular visits to physicians, dieticians, dedicated IBD nurses etc, and IBD-specific diagnostics include fecal calprotectin and endoscopy and increasingly ultrasound and magnetic resonance.

Contact person and coordinator for the IBD Alliance network

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Jonas Ludvigsson

Professor

Participants

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Sven Almer

Affiliated to Research
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Henrik Arnell

Affiliated to Research
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Johan Askling

Professor/Senior Physician
+46852483348
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Ann-Sofie Backman

Affiliated to Research
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Annika Bergquist

Professor/Senior Physician

Francesca Bresso

Affiliated to Research

Thomas Casswall

Affiliated to Research
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Charlotte Hedin

Adjunct Lecturer
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Helena Jonsson Rolandsdotter

Affiliated to Research

Marjo Kapraali

Affiliated to Research

Annika Karlsson

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Ulrik Lindforss

Affiliated to Teaching/Tutoring

Fredrik Lindgren

Lina Lindström

Mikael Lördal

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Petter Malmborg

Affiliated to Research
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Jenny Mjösberg

Professor
+46852482917

Natalia Mouratidou

Per Nilsson

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Ola Olén

Adjunct Senior Lecturer
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Mattias Svensson

Principal Researcher

Helena Thulin

Assistant Senior Lecturer
+46852483929

Ongoing projects

Ludvigsson, Jonas: network coordinator, KI,Risk of cancer in IBD - a registry-based study. The primary objective is to evaluate the risk of cancer in children and adults with IBD taking disease location, grade of inflammation and treatment into account.

Bresso, Francesca, KI: Role of epigenetic modifications in IBD. To evaluate epigenetic modifications in IBD, causative and regulatory role, related gene-environment interaction and identification of putative biomarkers

Ekbom, Anders, KI. Chronic inflammation - will it be less harmful after anti-inflammatory therapy? Follow-up of different patient groups with chronic inflammation with regards to morbidity, mortality utilization of health care, following different interventions, including surgery.

Hedin, Charlotte, KS. Altered intestinal microbiota and blood T-cell phenotype are shared by Crohn’s disease patients and their unaffected siblings: This project aimed to delineate the genetic, immune and microbiological profile of CD patients, their siblings and controls and also to determine which factors discriminate groups.

Lindström, Lina, KS. Recurrence of PSC after liver transplantation: The aim of the study is to identify/confirm risk factors for recurrent PSC in a large and well characterized cohort of PSC patients. Emphasis on IBD-related risk factors such as inflammatory activity and colectomy.

Malmborg, Petter, KS. Prognosis of pediatric IBD: Some studies suggest that childhood-onset of disease represents a more aggressive phenotype of IBD. We are studying the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County 1990-2007.

Olén, Ola, KI. Etiology of Inflammatory bowel disease  

-"'--"'- Prognosis of Inflammatory bowel disease

Selected publications

Association of inflammatory bowel disease in first-degree relatives with risk of colorectal cancer: A nationwide case-control study in Sweden.
Wang K, Olén O, Emilsson L, Khalili H, Halfvarson J, Song M, Ludvigsson JF
Int J Cancer 2023 Jun;152(11):2303-2313

Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis: A Scandinavian Cohort Study.
Olén O, Smedby KE, Erichsen R, Pedersen L, Halfvarson J, Hallqvist-Everhov Å, Bryder N, , Askling J, Ekbom A, Sachs MC, Sørensen HT, Ludvigsson JF
Clin Gastroenterol Hepatol 2023 Apr;():

The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis.
Kokkinou E, Soini T, Pandey RV, van Acker A, Theorell J, Czarnewski P, Kvedaraite E, Vandamme N, Lourda M, Sorini C, Weigel W, Carrasco A, Tibbitt CA, Schlums H, Lindforss U, Nordenvall C, Ljunggren M, Ideström M, Svensson M, Henter JI, Villablanca EJ, Bryceson YT, Rolandsdotter H, Mjösberg J
Cell Rep Med 2023 May;4(5):101038

Long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa: A population-based, sibling-controlled cohort study in Sweden.
Sun J, Fang F, Olén O, Song M, Halfvarson J, Roelstraete B, Khalili H, Ludvigsson JF
PLoS Med 2023 Feb;20(2):e1004185

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.
Moraes Holst L, Halfvarson J, Carlson M, Hedin C, Kruse R, Lindqvist CM, Bergemalm D, Almér S, Bresso F, Ling Lundström M, Repsilber D, D'Amato M, Keita Å, Hjortswang H, Söderholm J, Sundin J, Törnblom H, Simrén M, Strid H, Magnusson MK, Öhman L
Clin Exp Gastroenterol 2022 ;15():129-144

Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression?
Villablanca EJ, Selin K, Hedin CRH
Nat Rev Gastroenterol Hepatol 2022 Aug;19(8):493-507

Earnings during adulthood in patients with childhood-onset inflammatory bowel disease: a nationwide population-based cohort study.
Malmborg P, Everhov ÅH, Söderling J, Ludvigsson JF, Bruze G, Olén O
Aliment Pharmacol Ther 2022 Sep;56(6):1007-1017

Prevalence and Implications of Frailty in Older Adults With Incident Inflammatory Bowel Diseases: A Nationwide Cohort Study.
Kochar B, Jylhävä J, Söderling J, Ritchie CS, , Ludvigsson JF, Khalili H, Olén O
Clin Gastroenterol Hepatol 2022 Oct;20(10):2358-2365.e11

CD45RA+CD62L- ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs.
Kokkinou E, Pandey RV, Mazzurana L, Gutierrez-Perez I, Tibbitt CA, Weigel W, Soini T, Carrasco A, Rao A, Nagasawa M, Bal SM, Jangard M, Friberg D, Lindforss U, Nordenvall C, Ljunggren M, Haapaniemi S, Keita ÅV, Söderholm J, Hedin C, Spits H, Bryceson YT, Mjösberg J
Sci Immunol 2022 Apr;7(70):eabj8301

Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing.
Mazzurana L, Czarnewski P, Jonsson V, Wigge L, Ringnér M, Williams TC, Ravindran A, Björklund ÅK, Säfholm J, Nilsson G, Dahlén SE, Orre AC, Al-Ameri M, Höög C, Hedin C, Szczegielniak S, Almer S, Mjösberg J
Cell Res 2021 May;31(5):554-568

Läkemedel vid inflammatorisk tarmsjukdom (IBD) - behandlings­rekommendation

Keywords:
Celiac Disease Colitis, Microscopic Eosinophilia Epidemiology Fatty Liver Show all
JL
Content reviewer:
Jonas Ludvigsson
Gunilla Sonnebring
16-10-2024