Lars Engstrand Group
The work of our group aims at creating a scientific translational environment with a broad interdisciplinary approach to the interface between epidemiology and the microbiological, immunological and genetic aspects of chronic diseases in the gastrointestinal tract to clarify the pathogenic mechanisms and to improve the prospects for primary prevention.
The long-term objective is to identify and characterize factors (both microbial and host related) that determine or modify the excess risk of disease outcome observed in people infected with various pathogenic microorganisms in the gut. Identification and characterization of determinants of Helicobacter pylori -associated gastro-duodenal disease has been the main focus for > 20 years and the set-up of this project is an example how we promote interdepartmental and interdisciplinary collaborations. The projects combine population-based epidemiology for which the conditions in Sweden are uniquely favorable with clinical and basic microbiological science, including molecular biology and genomics.
Next generation sequencing, NGS-based microbial community analysis
PCR amplification, cloning and sequencing of 16S rRNA genes directly from the environment has revolutionized our understanding of microbial diversity. We have implemented the 16S sequencing approach in a high-throughput NGS format using the Illumina platform, enabling detailed analysis of a large amount of samples in parallel. We collaborate with a number of research groups in Sweden and abroad and a partly automated pipeline for microbiome profiling is now up-and-running at MTC and Science for Life Laboratory in Solna. Optimization of DNA-preparation, sequencing protocols and bioinformatics tools for analyses are ongoing and our goal is to establish a bioinformatic team dedicated to microbiology and microbiome projects at KI and SciLifeLab.
Dynamics and development of the human gut microbiota and its impact on health and disease
While the sequencing of the human genome has provided invaluable knowledge, it is difficult to change our own genetic makeup. The human microbiome, in contrast, is much more easily changed through simple means such as healthful probiotic cultures, bacteriotherapy and other lifestyle interventions. Up to 20 percent of the small molecules in our bloodstream appear to be synthesized by microbes. The microbiome thus may provide some of the most important medical breakthroughs of our era e.g. the human microbiome may be as important to our health as the human genome.
The long-term objective is to identify and characterize factors (both microbial and host related) that determine or modify the excess risk of disease outcome e.g. to determine the relationship between human health and changes in our gut microbiome. The projects combine population-based epidemiology, for which the conditions in Sweden are uniquely favorable, with clinical and basic microbiological science, including molecular biology and genomics. We have applied next generation sequencing platforms for large-scale studies of the human gut microbiome in health and disease (see above).
The establishment of the gut microbiome in early life is critical and microbiota disruption during this time-period could lead to metabolic consequences later in life. Factors such as antibiotic treatment and delivery by Caesarian section that could alter the intestinal microbiota have been investigated and long-term consequences of a disturbed microbiota i.e. dysbiosis are monitored in ongoing studies.
Characterization of the human gastric microbiota and lactobacilli involvement in gastrointestinal diseases
The discovery of Helicobacter pylori and the introduction of molecular-based methods to determine the microbiota have also increased the interest in studies of the gastric microbiota. The possible impact of the non-H. pylori microbiota in the stomach needs to be defined as well as options to manipulate the gastric microbiota to prevent gastro-duodenal diseases. There are still many questions to be answered. We do not know whether a majority of the non-H. pylori microbiota in the stomach colonizes or just pass the gastric niche and how acid suppressive drugs open up for bacterial overgrowth in the stomach. The aim is to narrow in on the true colonizers of the stomach e.g. the bacteria that interacts and may be involved in pathogenesis of atrophic gastritis and gastric cancer. We will also determine the lactobacilli population present in the human stomach and if lactobacilli co-exist with H. pylori and adhere to human gastric mucus. If this is the case we will investigate if these lactobacilli have antagonistic effects on H. pylori. Thus, administration of lactobacilli to H. pylori-infected individuals may become an alternative treatment option for these patients.
Evolution of Helicobacter pylori and its significance in the development of gastric cancer
H. pylori infection has been estimated to contribute to about 65% and 80% of non-cardia gastric cancers in developed and less developed countries, respectively. H. pylori colonize approximately 3 billions people, whereas only 1 million incident gastric cancers occur each year nowadays. The genetic determinants, from both the bacterial and the host, that have an impact on the gastric cancer outcome of H. pylori infection have been less studied compared to the peptic ulcer disease link. The dynamic picture of bacterial-host interaction that usually lasts for decades raises obstacle in exploring the etiology of H. pylori-associated gastric cancer. Using archived formalin-fixed paraffin-embedded biopsies, and the unique Swedish national registers together with unique long-term follow up samples we aim to identify the genetic determinants for gastric cancer at the whole-bacterial-genome level, as well as important host-genetic factors from the host.
Project Leaders in the Lars Engstrand Group
The Centre for Translational Microbiome Research (CTMR)
CTMR aims to better understand the contribution of the human microbiome to physiology and pathophysiology with the goal to open opportunities for development of novel therapies in the area of gastroenterology, reproductive health and neonatology.
The Clinical Genomics facility
The Clinical Genomics facility provides a dedicated research infrastructure for projects utilising massively parallel sequencing technologies. All projects are carried out in close collaboration with the Swedish healthcare system. The facility serves as a competence center assisting the translation of genomics-based tools to routine clinical care. All work is carried out in close collaboration with medical expertise provided by the clinical diagnostic laboratories and patients’ managing physicians. Also, the facility aims to improve the capacity of the public health microbiology for national surveillance of infectious diseases and for epidemic preparedness.
Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden.
Brusselaers N, Wahlin K, Engstrand L, Lagergren J
BMJ Open 2017 Oct;7(10):e017739
Lars EngstrandAvdelningschef, Professor/överläkare
Ina Schuppe KoistinenDirektör
Johanna SiminDoktorand, Forskarstuderande
Jing WangForskningsassistent, UF
Luisa Warchavchik HugerthPostdoc
- Adam Carstens, Associated PhD student
Collaborations and Group Funding
Cross-departmental collaborations have been developed with a number research centers, including the Dept. of Medicine, Baylor College of Medicine (David Graham), Houston, Tx, Center for Genome Sciences and Systems Biology (Jeffrey Gordon), Washington University School of Medicine, St. Louis, and Dept. of Medicine, New York University School of Medicine (Martin Blaser), NY, USA. Lars Engstrand has faculty positions (adjunct professor) at these three universities with co-PI positions in collaboration projects. We have also collaborations with a number of research groups in Sweden including translational research projects within the Clinical Genomics facility organization. Some Swedish collaborators in the microbiology field are Weimin Ye, Olof Nyren, Lars Agreus and Mauro DAmato (KI), Jonas Halvarsson (Örebro), Andreas Matussek (Jönköping), Mathias Uhlén, Anders Andersson (KTH, Stockholm), Hilpi Rautelin, Dan Andersson, Åke Gustavsson (Uppsala), Jens Nielsen (Chalmers, Gothenburg), Håkan Hanberger (Linköping), Thomas Borén (Umeå), Helena Enroth (Skövde) and Karin Tegmark-Wisell (Public Healt Agency, Stockholm). Lars Engstrand was appointed Director of Center for Translational Microbiome Research, CTMR - an open academic research collaboration between Ferring Pharmaceuticals and Lars Engstrands group at KI
Projects in Lars Engstrand´s group receive funding from the following sources:
- Karolinska Institutet
- Ferring Pharmaceuticals
- Vetenskapsrådet - The Swedish Research Council
- Söderbergs stiftelse