Research group Charlotte Hedin

We are “the Karolinska Gut Group”. Our research deals with all things within luminal gastroenterology. We have a broad portfolio of projects and group members with clinical work at both the Karolinska, Ersta Hospital and Gastromottagning City. Within the group is associate professor Peter Thelin Schmidt, two adjunct lectors, five PhD students and four affiliated members.

Luminal gastroenterology

Our research covers a range of areas within gastroenterology including inflammatory bowel disease (IBD), diverticular disease, endoscopic techniques, nutrition in chronic fatigue syndrome and colon cancer – including hereditary cancers such as Lynch syndrome.

Within the area of IBD we drive translational and register based studies. A major goal for our IBD research programme is to delineate the molecular and nutritional pathways that underpin mucosal healing. Furthermore, we aim to determine pathogenic factors including the role of genetics, environmental factors, luminal microbiota and gut permeability in the the pathogenesis of Crohn’s disease by studying a cohort of patients and their healthy siblings.

In endoscopy, we investigate whether patients with IBD have a greater risk of complications during colonoscopy. In another endoscopy-based project we evaluate a newly developed method for examination, treatment and screening of pre-stages of anal cancer. Many patients develop IBD as children. Together with implementation experts, we are carrying out a research project on improved transfer from a paediatric clinic to an adult clinic.

Within the field of hereditary cancer our goal is to shed light on a relatively new branch within the field of gastroenterology, i.e. oncogastroenterology, and to establish evidence based clinical routines regarding preventive treatment and surveillance of the patients with hereditary risk genes for colorectal cancer.

“The Karolinska Gut Group” is also a key centre for several national IBD projects, with me (Charlotte Hedin) on the steering committee for projects within the Swedish Organisation for the Study of IBD (SOIBD). We are also actively participating in international projects including the Health Outcomes Observatories and the GEM Project.

Ongoing projects

One of our central IBD studies is aimed to answer the question “how does the gut heal?” with longitudinal RNA sequencing in patients with acute severe ulcerative colitis – documenting the molecular pathways that lead them into remission.

Most treatments for IBD (as with most immune-mediated diseases) are based on immunosuppression, with consequent side effects of neoplasia and infection. Delineating and harnessing the healing power of the gut will open the possibility to treat IBD without immunosuppression – a concept we laid out in our article “Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression?” published in Nature Reviews in Gastroenterology and Hepatology. This project represents a significant collaboration with Eduardo Villablanca’s research group Immunology and allergy (“the Villablanca lab”).

Our clinical studies form a large part of our work and we are currently driving a study into the optimal use of patient reported outcome measures (PROM). PROMs are standardised validated questionnaire surveys assess the quality of care delivered to patients from the patient perspective. PROM are gaining increasing acceptance as a key outcome measure in clinical trials. However, their optimal implementation (how often, which patient groups, what kind of questions) has yet to be determined. As the Swedish IBD register has included PROM measures for many years, we in Sweden have an excellent resource to make this contribution to IBD knowledge.

Within the field of oncogastroenterology our capacity to identify individuals with hereditary risk genes for colorectal cancer has improved, and there is now a need to elucidate and study strategies of how to prevent colorectal cancer CRC in the most efficient way in this young group. Within the group we run both academic pharmaceutical phase II trials and industry sponsored phase I trials to evaluate new treatments and we have initiated health economic studies of different endoscopic surveillance strategies.

Group members

Charlotte Hedin

Adjunct lecturer/Research group leader.

Cooperation

National:

Swedish Inception Cohort (SIC) and Biologic treated IBD patients (BIO-IBD): The purpose of the study is to identify new biomarkers for diagnosis, response to therapy and prediction of the course of the disease within IBD. We have recruited a large cohort of both newly diagnosed patients and patients starting with new biological drugs from several hospitals throughout Sweden. From these patients we have collected an extensive biobank of biological material. Recruitment of "discovery" cohorts is complete, and the final phase of analysis has begun. We aim at utilization and implementation of these new biomarkers in collaboration with the Swedish biomedical industry sector. https://www.soibd.se/

International:

GEM study in Sweden. GEM (Genetics, Environment and Microbiota) is a study in which healthy siblings of IBD patients are recruited and biomarkers of risk for IBD are studied. Siblings are then followed for up to 6 years to detect newly debuted IBD. The comparison of siblings who later develop IBD with those who remain healthy isexpected to generate disease risk biomarkers that can be used to treat disease before intestinal injuries have occurred, or even prevent disease progression. Completed recruitment in 2019, ongoing follow-up of study participants. http://www.gemproject.ca/

Health Outcomes Observatories (H2O): This EU-funded initiative seeks to define patient reported outcome measures (PROM) that allow patients to report their experience of their disease in a standardised way. This project will also develop technological solutions including an App to facilitate implementation of the PROM in clinical practice. Uniquely, this project is a collaboration across several chronic diseases including IBD, cancer and diabetes, facilitating future research that will provide cross-fertilisation between these disease areas. https://health-outcomes-observatory.eu/

The NORDTREAT project will build on the progress of recent major European initiatives that include interdisciplinary collaborations between academia, hospitals, biomedical companies and patient organizations. The overall goal is to improve the patient's prognosis for IBD and quality of life by introducing a new personalized medical algorithm based on newly generated “-omics” data. Patients with newly discovered IBD at centers in the Nordic countries will be offered individualized treatment based on a protein profile in the blood. Patients at risk of serious illness receive so-called "top-down" treatment, with an anti-tumor necrosis factor drug. The outcome after 1 year is compared with the current treatment where medication is gradually stepped up. In the long term, we intend to seek to develop a simple test based on the markers in order to implement this in healthcare and improve patients' quality of life. https://www.oru.se/NORDTREAT

Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome (MesaCAPP) Sponsor: Ann-Sofie Backman.
Collaborator: The Swedish Research Council. This is a multicenter, multinational, randomized, 2-arm, double-blind, phase II clinical study with 2000mg mesalamine (5-ASA) or placebo in LS patients for a 2-year treatment. 260 tumor free carriers of a known genetic mutation in a major MMR gene (including patients in which the polyps are endoscopically removed) will be randomized 1:1 to receive 2000mg mesalamine or placebo. Patients will be identified through local or national registries and through collaboration with sites. Tumor free patients, assessed by white light high resolution colonoscopy, will be randomized to the study. Blood and stool samples will be collected for analysis of microbiota, ctDNA and potential biomarkers. Biopsies of the normal tissue of ascending colon and rectum will be taken at the first and the last colonoscopy.

The aim of the study is to investigate the effect of regular treatment with mesalamine (5-ASA) on the occurrence of any colorectal neoplasia, tumor multiplicity (the number of detected adenomas/carcinomas) and tumor progression in LS patients. Tumor multiplicity and tumor progression (severity of the neoplastic lesions) will be investigated. https://clinicaltrials.gov/ct2/show/NCT04920149

Research support

  • Donald Grant and Ann Martin Calder Foundation.
  • Bengt Ihre Fonden.
  • ECCO Grant.
  • Gastrofonden.
  • Mag-Tarmfonden.
  • Nanna Svartz Fond.
  • Ruth och Richard Julins Stiftelse.

Selected publications

Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression?
Villablanca EJ, Selin K, Hedin CRH
Nat Rev Gastroenterol Hepatol 2022 Apr;():

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

Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial.
Forsberg A, Westerberg M, Metcalfe C, Steele R, Blom J, Engstrand L, Fritzell K, Hellström M, Levin LÅ, Löwbeer C, Pischel A, Strömberg U, Törnberg S, Wengström Y, Ekbom A, Holmberg L, Hultcrantz R
Lancet Gastroenterol Hepatol 2022 Mar;():

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 05;31(5):554-568

Measuring the impact of gastrointestinal inconvenience and symptoms on perceived health in the general population - validation of the Short Health Scale for gastrointestinal symptoms (SHS-GI).
Walter S, Jones MP, Sjödahl J, Stjernman H, Hjortswang H, Andreasson A
Scand J Gastroenterol 2021 Dec;56(12):1406-1413

Older age is a risk factor for inadequate energy intake during acute, severe IBD and is associated with shorter time to relapse.
Kulmala KA, Björk J, Andersson S, Backman AS, Eberhardson M, Bresso F, Hedin CRH
Scand J Gastroenterol 2020 Oct;55(10):1185-1192

Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis.
Hedin CRH, Sado G, Ndegwa N, Lytvyak E, Mason A, Montano-Loza A, Gerussi A, Saffioti F, Thorburn D, Nilsson E, Larsson G, Moum BA, van Munster KN, Ponsioen CY, Levy C, Nogueira NF, Bowlus CL, Gotlieb N, Shibolet O, Lynch KD, Chapman RW, Rupp C, Vesterhus M, Jørgensen KK, Rorsman F, Schramm C, Sabino J, Vermeire S, Zago A, Cazzagon N, Marschall HU, Ytting H, Ben Belkacem K, Chazouilleres O, Almer S, , Bergquist A
Clin Gastroenterol Hepatol 2020 09;18(10):2295-2304.e2

Gender, having a positive FIT and type of hospital are important factors for colonoscopy experience in colorectal cancer screening - findings from the SCREESCO study.
Fritzell K, Forsberg A, Wangmar J, Wengström Y, Bottai M, Hultcrantz R
Scand J Gastroenterol 2020 Nov;55(11):1354-1362

Detailed transcriptional landscape of peripheral blood points to increased neutrophil activation in treatment-naïve inflammatory bowel disease.
Juzenas S, Hübenthal M, Lindqvist CM, Kruse R, Steiert TA, Degenhardt F, Schulte D, Nikolaus S, Zeissig S, Bergemalm D, Almer S, Hjortswang H, Bresso F, , Strüning N, Kupcinskas J, Keller A, Lieb W, Rosenstiel P, Schreiber S, D'Amato M, Halfvarson J, Hemmrich-Stanisak G, Franke A
J Crohns Colitis 2022 Jan;():

High-Definition Chromoendoscopy Superior to High-Definition White-Light Endoscopy in Surveillance of Inflammatory Bowel Diseases in a Randomized Trial.
Alexandersson B, Hamad Y, Andreasson A, Rubio CA, Ando Y, Tanaka K, Ichiya T, Rezaie R, Schmidt PT
Clin Gastroenterol Hepatol 2020 08;18(9):2101-2107