Full publications

8. Magnusson et al. Inflamm Bowel Dis Volume 0, Number 0, Month 2017; The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis

Abstract

Background:

The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host’s immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course.

Methods:

Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44).

Results:

At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R = 0.395, P < 0.0001).

Conclusions:

In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.

 

7. Bennet, Sean MP, et al. Gut 2017;0:1–10. Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs

Abstract

Objective

The effects of dietary interventions on gut bacteria are ambiguous. Following a previous intervention study, we aimed to determine how differing diets impact gut bacteria and if bacterial profiles predict intervention response.

Design

Sixty-seven patients with IBS were randomised to traditional IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4 days during screening and intervention. Faecal samples and IBS Symptom Severity Score (IBS-SSS) reports were collected before (baseline) and after intervention. A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial composition. Per protocol analysis was performed on 61 patients from whom microbiome data were available.

Results

Responders (reduced IBS-SSS by ≥50) to low FODMAP, but not traditional, dietary intervention were discriminated from non-responders before and after intervention based on faecal bacterial profiles. Bacterial abundance tended to be higher in non-responders to a low FODMAP diet compared with responders before and after intervention. A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional IBS diet had higher DI scores than responders at baseline. Finally, while a traditional IBS diet was not associated with significant reduction of investigated bacteria, a low FODMAP diet was associated with reduced Bifidobacterium and Actinobacteria in patients, correlating with lactose consumption.

Conclusions

A low FODMAP, but not a traditional IBS diet may have significant impact on faecal bacteria. Responsiveness to a low FODMAP diet intervention may be predicted by faecal bacterial profiles.

 

6. Andréasson et al. Arthritis Research & Therapy (2016) 18:278; Intestinal dysbiosis is common in systemic sclerosis and associated with gastrointestinal and extraintestinal features of disease

Abstract

Background

Recent evidence suggests a link between autoimmunity and the intestinal microbial composition in several rheumatic diseases including systemic sclerosis (SSc). The objective of this study was to investigate the prevalence of intestinal dysbiosis in SSc and to characterise patients suffering from this potentially immunomodulatory deviation.

Methods

This study consisted of 98 consecutive patients subject to in-hospital care. Stool samples were analysed for intestinal microbiota composition using a validated genome-based microbiota test (GA-map™ Dysbiosis Test, Genetic Analysis, Oslo, Norway). Gut microbiota dysbiosis was found present as per this standardised test. Patients were examined regarding gastrointestinal and extraintestinal manifestations of SSc by clinical, laboratory, and radiological measures including esophageal cineradiography, the Malnutrition Universal Screening Tool (MUST), levels of plasma transthyretin (a marker of malnutrition) and faecal (F-) calprotectin (a marker of intestinal inflammation).

Results

A majority (75.5%) of the patients exhibited dysbiosis. Dysbiosis was more severe (rs = 0.31, p = 0.001) and more common (p = 0.013) in patients with esophageal dysmotility. Dysbiosis was also more pronounced in patients with abnormal plasma levels of transthyretin (p = 0.045) or micronutrient deficiency (p = 0.009). In 19 patients at risk for malnutrition according to the MUST, 18 exhibited dysbiosis. Conversely, of the 24 patients with a negative dysbiosis test, only one was at risk for malnutrition. The mean ± SEM levels of F-calprotectin were 112 ± 14 and 45 ± 8 μg/g in patients with a positive and negative dysbiosis test, respectively. Dysbiosis was more severe in patients with skin telangiectasias (p = 0.020), pitting scars (p = 0.023), pulmonary fibrosis (p = 0.009), and elevated serum markers of inflammation (p < 0.001). However, dysbiosis did not correlate with age, disease duration, disease subtype, or extent of skin fibrosis.

Conclusions

In this cross-sectional study, intestinal dysbiosis was common in patients with SSc and was associated with gastrointestinal dysfunction, malnutrition and with some inflammatory, fibrotic and vascular extraintestinal features of SSc. Further studies are needed to elucidate the potential causal relationship of intestinal microbe-host interaction in this autoimmune disease.

 

5. Magnusson et al. J Crohns Colitis. 2016 Aug;10(8):943-52; Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition

Abstract

Background and Aims:

Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome.

Methods:

Serum and biopsies were obtained from UC patients naïve to biological therapy [ n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12–14 weeks after baseline.

Results:

At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitziiincreased during induction therapy in responders.

Conclusions:

Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

 

4. Vebø et al. Journal of Microbiological Methods 129 (2016) 78–80; Bead-beating artefacts in the Bacteroidetes to Firmicutes ratio of the human stool metagenome

Abstract

We evaluated bead-beating cell-lysis in analyzing the human stool metagenome, since this is a key step. We observed that two different bead-beating instruments from the same producer gave a three-fold difference in the Bacteroidetes to Firmicutes ratio. This illustrates that bead-beating can have a major impact on downstream metagenome analyses.

 

3. Casén et al. Aliment Pharmacol Ther 2015. 42: 71–83; Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD

Abstract

Background

Dysbiosis is associated with many diseases, including irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD), obesity and diabetes. Potential clinical impact of imbalance in the intestinal microbiota suggests need for new standardized diagnostic methods to facilitate microbiome profiling.

Aim

To develop and validate a novel diagnostic test using faecal samples to profile the intestinal microbiota and identify and characterize dysbiosis.

Methods

Fifty‐four DNA probes targeting ≥300 bacteria on different taxonomic levels were selected based on ability to distinguish between healthy controls and IBS patients in faecal samples. Overall, 165 healthy controls (normobiotic reference collection) were used to develop a dysbiosis model with a bacterial profile and Dysbiosis Index score output. The model algorithmically assesses faecal bacterial abundance and profile, and potential clinically relevant deviation in the microbiome from normobiosis. This model was tested in different samples from healthy volunteers and IBS and IBD patients (n = 330) to determine the ability to detect dysbiosis.

Results

Validation confirms dysbiosis was detected in 73% of IBS patients, 70% of treatment‐naïve IBD patients and 80% of IBD patients in remission, vs. 16% of healthy individuals. Comparison of deep sequencing and the GA‐map Dysbiosis Test, (Genetic Analysis AS, Oslo, Norway) illustrated good agreement in bacterial capture; the latter showing higher resolution by targeting pre‐determined highly relevant bacteria.

Conclusions

The GA‐map Dysbiosis Test identifies and characterises dysbiosis in IBS and IBD patients, and provides insight into a patient’s intestinal microbiota. Evaluating microbiota as a diagnostic strategy may allow monitoring of prescribed treatment regimens and improvement in new therapeutic approaches.

 

2. Thorkildsen et al. Gastroenterology Research and Practice Volume 2013, Article ID 636785, 13 pages Dominant Fecal Microbiota in Newly Diagnosed Untreated Inflammatory Bowel Disease Patients

Abstract

Our knowledge about the microbiota associated with the onset of IBD is limited. The aim of our study was to investigate the correlation between IBD and the fecal microbiota for early diagnosed untreated patients. The fecal samples used were a part of the Inflammatory Bowel South-Eastern Norway II (IBSEN II) study and were collected from CD patients (), UC patients (), unclassified IBD (IBDU) patients (), and from a control group (). The bacteria associated with the fecal samples were analyzed using a direct 16S rRNA gene-sequencing approach combined with a multivariate curve resolution (MCR) analysis. In addition, a 16S rRNA gene clone library was prepared for the construction of bacteria-specific gene-targeted single nucleotide primer extension (SNuPE) probes. The MCR analysis resulted in the recovery of five pure components of the dominant bacteria present: Escherichia/Shigella, Faecalibacterium, Bacteroides, and two components of unclassified Clostridiales. Escherichia/Shigella was found to be significantly increased in CD patients compared to control subjects, and Faecalibacterium was found to be significantly reduced in CD patients compared to both UC patients and control subjects. Furthermore, a SNuPE probe specific for Escherichia/Shigella showed a significant overrepresentation of Escherichia/Shigella in CD patients compared to control subjects. In conclusion, samples from CD patients exhibited an increase in Escherichia/Shigella and a decrease in Faecalibacterium indicating that the onset of the disease is associated with an increase in proinflammatory and a decrease in anti-inflammatory bacteria.

 

1. Vebø et al. Clinical Vaccine Immunology. Aug. 2011, p. 1326–1335; Temporal Development of the Infant Gut Microbiota in Immunoglobulin E-Sensitized and Nonsensitized Children Determined by the GA-Map Infant Array

Abstract

At birth, the human infant gut is sterile, but it becomes fully colonized within a few days. This initial colonization process has a major impact on immune development. Our knowledge about the correlations between aberrant colonization patterns and immunological diseases, however, is limited. The aim of the present work was to develop the GA-map (Genetic Analysis microbiota array platform) infant array and to use this array to compare the temporal development of the gut microbiota in IgE-sensitized and nonsensitized children during the first 2 years of life. The GA-map infant array is composed of highly specific 16S rRNA gene-targeted single nucleotide primer extension (SNuPE) probes, which were designed based on extensive infant 16S rRNA gene sequence libraries. For the clinical screening, we analyzed 216 fecal samples collected from a cohort of 47 infants (16 sensitized and 31 nonsensitized) from 1 day to 2 years of age. The results showed that at a high taxonomic level, Actinobacteria was significantly overrepresented at 4 months while Firmicutes was significantly overrepresented at 1 year for the sensitized children. At a lower taxonomic level, for the sensitized group, we found that Bifidobacterium longum was significantly overrepresented at the age of 1 year and Enterococcus at the age of 4 months. For most phyla, however, there were consistent differences in composition between age groups, irrespective of the sensitization state. The main age patterns were a rapid decrease in staphylococci from 10 days to 4 months and a peak of bifidobacteria and bacteroides at 4 months. In conclusion, our analyses showed consistent microbiota colonization and IgE sensitization patterns that can be important for understanding both normal and diseased immunological development in infants.

 

Books and book chapters

1. Casén C. Textbook “Microbiology: an Evolving Science”. Chapter 28 opening research highlight and interview; ‘Clinical Microbiology and Epidemiology’, 2016;

Prof John W. Foster, Dept of Microbiology and Immunology College of Medicine, University of South Alabama

 

Posters and Presentations

25. Accepted abstract (oral) PIBD Sept 2017; Dr Christine Olbjørn, NO; Faecal microbiota dysbiosis in paediatric inflammatory bowel disease persists after therapy

24. Poster DDW May 2017; Dr Christine Olbjørn, NO; Microbial characterization of pediatric inflammatory bowel disease and stratification into disease severity groups

23. Oral presentation DDW May 2017; Dr Jørgen Valeur, NO; Microbial DNA markers associated with response to a low FODMAP diet in patients with irritable bowel syndrome

22. Poster ECCO Feb 2017; Dr Petr Ricanek, NO; Microbiota related disease activity and distribution in subgroups of IBD

21. Poster ECCO Feb 2017; Dr Christine Olbjørn, NO Microbial characterization of paediatric inflammatory bowel disease and stratification into disease severity groups

20. Oral presentation UEGW Oct 2016; Sean Bennet, SE (Awarded one of top 5 abstracts) Multivariate modelling of gut microbial profiles predicts responsiveness to a diet low in FODMAPs

19. Poster UEGW Oct 2016; German multicenter study, Prof Wolfgang Kruis, Köln, GE; Performance Evaluation of Dysbiosis Status as A Tool For Clinical Investigation In Patients With Functional Gastrointestinal Disorders

18. Oral Presentation UEGW Oct 2016; Dr Petr Ricanek, NO; Microbiota Alterations In Treatment Naïve IBD and Non-IBD Patients – The EU IBD-Character Project

17. Oral Presentation UEGW Oct 2016; Rebiotix, Courtney Jones, USA; Rebiotix – Consistent and Reproducible Production of a Microbiota-based Drug for Recurrent C . difficile Infection: Application of a Novel Diagnostic for Dysbiosis

16. Poster UEGW Oct 2016; Dr Jostein Sauar, NO; Dysbiosis and stability over 2 years in patients with irritable bowel syndrome

15. Poster UEGW Amsterdam Oct 2012; Caroline Frøyland, NO; Development of a new, rapid gut microbiota test for analysis of IBD (GA)

14. Poster UEGW Oct 2016; Tonje Hustoft, NO; IBS patients on 3 weeks Low FODMAP Diet followed by 3 weeks High FODMAP Diet

13. Oral Presentation UEGW Oct 2016; Dr Tarek Mazzawi, NO; IBS and Fecal Microbiota Transplant (FMT)

12. Presentation ECCO Amsterdam March 2016, Christina Casen, NO; A novel diagnostic test for determining microbial dysbiosis

11. Oral present ECCO Amsterdam March 2016, Petr Ricanek, NO; Microbiota profiles in treatment naïve Norwegian IBD and non IBD patients.

10. Poster ICMI Seattle 2015; Prof Lena Öhman, Gothenburg, SE; The importance of the mucosal antimicrobial peptide expression and gut microbiota in anti-TNF therapy response in ulcerative colitis

9. Poster Targeting Microbiota, Paris Oct 2015; Caroline J Frøyland (GA); Stability of repeated fecal DNA preparation using the GA-map™ Dysbiosis Test

8. Poster UEGW Vienna Oct 2014; Dr Jorgen Valeur, Oslo, NO; Influence of a low-FODMAP diet on symptoms and gut microbiota in patients with irritable bowel syndrome

7. Poster UEGW Vienna 2014; Dr Kristoffer Kofod Vinding, DK; Gut Microbiota alterations in IBS patients before and after 6 weeks of low FODMAP diet versus Lactobacillus Rhamnosus GG

6. Poster DDW Chicago 2014; Dr Natalia Pedersen, DK; Gut microbiota in IBD patients with IBS before and after 6 weeks of low FODMAP diet

5. Poster ECCO Copenhagen Feb 2014; Dr Finn T. Hegge, NO; Microbiota stability in vivo and in vitro (GA)

4. Poster ECCO Copenhagen Feb 2014; Dr Natalia Pedersen, DK; Gut microbiota alterations in IBD patients with IBS symptoms before and after 6 weeks of low FODMAP diet

3. Poster UEGW Berlin Oct 2013; Dr Heidi Vebø, NO; Microbiota analysis in IBS and IBD/non-IBD patients and normal subjects (GA)

2. Poster DDW Orlando May 2013; Dr Heidi Vebø, NO; New test for profiling of the gut microbiota in IBS, non-IBD and IBD patients (GA)

1. Poster ECCO Vienna Feb 2013; Dr Heidi Vebø, NO; New test for profiling of the gut microbiota in non-IBD and IBD patients (GA)

# Last update May 2017