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CTMR research in gastroenterology

The gastrointestinal tract harbors a divers and host-specific gut microbial community that significantly contributes to the maintenance of GI health but also to disease development. CTMR research examines the possible role of the gut microbiome in inflammatory diseases and also neoplastic GI diseases with the goal to understand the biology and to identify future diagnostic and therapeutic targets.

Research questions:

  • What composition of the gastrointestinal microbiome is normal in healthy individuals?
  • Does providing maternal vaginal and gut microbiota to neonates delivered by elective caesarian sections restore the microbiota development during infancy and reduces allergy development in children?
  • To what extent is the composition of the microbiome altered by invading pathogens, and altered environmental conditions in the gut.
  • Is the microenvironment of the gut mucosa in tissues with IBD, diverticulosis and polyps/tumours colonized with different microbes compared to healthy mucosa?
  • What is the composition of the gut microbiome in children with IBD compared to healthy children?
  • Can we identify microbial biomarkers to improve the diagnosis of IBD?
  • Can we change a dysbiotic gut microbial profile to a healthy profile to cure IBD?
  • How do commonly prescribed drugs, diet and other factors affect the gut microbiome composition and function, and how does this affect health?

Projects

A large number of well-defined clinical cohorts and basic research projects are used to answer our research questions. Four examples are briefly described her.

PopCol

Clinical collaborator: Prof Lars Agreus, Karolinska Institutet

 

The PopCol (Population based Colonoscopy) study was performed in Stockholm, Sweden and recruited a random sample of 3,556 adults. Colonoscopy with biopsy sampling from 5 locations in the large bowel was performed in 745 subjects. In addition, fecal samples were obtained from 520 subjects with a follow-up sample from 285 subjects four years later. All biopsies were analysed and scored for inflammation by one pathologist. In addition to the microbial samples, volunteers in the PopCol study filled extensive questionnaires on their health, lifestyle and bowel habits. The colonoscopic investigation also provided information on the state of the subjects colonic health, including the presence of polyps, diverticula, inflammation and adenomas. The mucosal associated microbiome and fecal samples were analysed using 16S rRNA gene sequencing. The data provide a definition of the normal microbiome in the lower GI tract of healthy individuals and will be used as baseline for other studies, e.g. with patients diagnosed with inflammatory bowel disease.

RoMaNs - Restoration of Microbiota in Newborns

Cesarean section (CS) born babies do not have the same exposure to maternal vaginal and fecal contents and the bacteria colonizing multiple body sites at birth as vaginally born babies. In this study we aim to investigate whether providing maternal vaginal and gut microbiota to neonates delivered by elective CS restores the microbiota development during infancy and reduces allergy development in children. To do this, we will compare the community structure of microbes from mothers and their babies in multiple body sites during the first 2 years of life of infants born vaginally or via scheduled CS with or without exposure to the vaginal and fecal environment. We aim for 100 babies in each group and recruitment is currently ongoing at several hospitals around Sweden.

Paediatric IBD: Importance of microbiome for remission after enteral nutrition treatment in children with IBD

Clinical collaborator: Niklas Nyström, Uppsala Akademiska Sjukuset/Uppsala University

 

Exclusive enteral nutrition therapy (EEN) has similar anti-inflammatory effect as systemic steroids and is free from the infamous steroid induced adverse effects and has been found an effective treatment in paediatric Crohn’s disease (CD) albeit the mechanism is unclear. CD is characterized by an abnormal intestinal microbiome. It is also well known that diet is one of the decisive factors for the intestinal microbiome composition so that a radical change in diet can bring a prompt and radical change in the intestinal microbiome. There are some indications that EEN can change the intestinal microbiome in patients with CD but further evidence is warranted. In an observational study on 50 children with IBD treated with enteral nutrition, intestinal biopsies were collected before and after treatment for analyses of microbiota composition. In addition, samples were analysed from 150 treatment-naïve children diagnosed with IBD and non-IBD controls. The goal of the study is to define the microbiome in paediatric IBD patients and to study the effect of the nutritional intervention.

KOLBIBAKT: A study on the association of the microbiome of the large intestine to colorectal diseases

Clinical collaborator: Ulf Gustafsson, Danderyds Sjukhus/Karolinska Institutet

 

The aetiology of colorectal diseases such as IBD, diverticular disease, metaplasia/colorectal cancer and IBS needs further investigation. To enable comparisons of intestinal microbiota between different diseases a biobank with patients undergoing a colonoscopy at Danderyd’s hospital was set up. As controls both patients undergoing screening without symptomatology and colonoscopy findings and healthy participants from the PopCol study are used. Danderyds Sjukhus performs 2500 colonoscopies per year and patients are invited to fill in the comprehensive study questionnaire and donate blood samples, fecal samples and biopsies. For each participant, 2 biopsies are taken from caecum, one for DNA/RNA and one for cultivation and 2 additional biospies are taken from the diseased areas. So far, approximately 1000 patients have been recruited to the study with the following frequencies: colorectal cancer 5%, polyps 30%, IBD 15%, diverticulosis 30%, healthy 15%. Patient recruitment will be ongoing until the number of 1500 is reached.