Lars Engstrand Group

The human intestinal microbiome, Helicobacter pylori and gastrointestinal disease development


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 to promote interdepartmental and interdisciplinary collaboration. The project combines population-based epidemiology for which the conditions in Sweden are uniquely favorable with clinical and basic microbiological science, including molecular biology and genomics.

Given the genetic diversity of humans and microorganisms, arguably the ideal epidemiologic study of the association between infection and disease outcome, is a prospective case-control study, restricted to a defined catchment area that is representative of a homogenous indigenous population. We have performed a number of such studies and achieved representative material (fecal, whole blood, serum and tissue samples) from cases and controls. We are also involved in several prospective ongoing studies aimed to study inflammatory bowel disease, early establishment of the gut microbiota in children and colonization resistance. The projects aim at defining molecular determinants for microbial pathology and are based on three components, each illustrating how host, microbial and environmental factors, respectively, may alter the outcome of infection. Genetically well defined and manipulable animal models, employing extensively genotyped clinical isolates of single microorganisms or well characterized microbiomes, are used and provide an attractive in vivo test tube for describing the molecular details of an evolving infection, from both the host and microbial perspective.

Project Groups within the Lars Engstrand Group

Sven Hoffner Project


The Centre for Translational Microbiome Research (CTMR)

The Centre for Translational Microbiome Research (CTMR) website

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

Clinical Genomics facility in Stockholm was established in 2013 as a spin out from the NGI facility due to the increased demand of services from the health care setting and the need to establish at SciLifeLab a service profile specifically addressing the needs of translational research and the health care setting. MTC/Karolinska Institutet is the host department for Clinical Genomics since 2014.

Lars Engstrand is Director for this facility and overall responsible for the activities at the facility, communications within SciLifeLab and KI (including the Board and Director), communication and outreach activities and strategic discussions with clinical collaborators.

The activities within the Clinical Genomics facility are centered around applying and validating high-throughput genomic technologies for future implementation into clinical diagnostics within the health-care system. In detail, we cover the following three types of projects: i) direct transfer of high-throughput technology into routine diagnostics, ii) development of a high-throughput analysis with an expected utility in routine diagnostics, and iii) high profile translational research with a future potential application in clinical diagnostics.

Clinical Genomics in Stockholm has during the first year of operations focused on establishing the infrastructure for operations and a quality assurance system following the ISO/IEC 17025 standard, as well as setting up experimental and analytical capability for inherited diseases and microbial genomics. On the experimental side we are now delivering exomes at a pace and quality required for this type of translational and diagnostic sequencing (>99.5% coverage, turn-around time in 3-4 days if needed), and we are preparing for a switch to whole genome sequencing. On the analytical side we have developed an in-house data processing capability starting with the raw data from the sequence run and processing the data all the way to ranked variants ready for clinical interpretation and decision making. A key challenge has been the development of an analytical pipeline that provides results quickly enough, also for whole genome data. Current estimates indicate that it will be possible to reduce the processing time to ca 6 hours for exome level data, and 24-30 hours for whole genome data. We have also developed a set of support tools for clinical decision making, enabling clinical collaborators to view the results without requirement of in-depth bioinformatic knowledge. Further, we have established the principle of acute setting whole genome sequencing providing clinical answers starting at 15 hours after sample has been received. This provides a foundation for a new strategy for diagnostics and treatment choices for acute setting metabolic medicine.   

We have also established a basic capability for microbial diversity characterisation and monitoring of transmission and outbreak routes in epidemiological and hospital settings.

The facility is currently also engaged in several cancer projects and aiming for identification of personalised treatment and prognosis strategies. These projects are expected to be carried out during 2015 and focus on five different cancers; breast, colon, lung, pancreas and pediatric neuroblastoma. Finally, the facility will also start providing non-invasive prenatal testing together with Klinisk Genetik at Karolinska university hospital.

Further development of the technology used by the facility is a central aspect of the work carried out. There are numerous ways how this is done.

  1. We carry out internal development to both establish new assays and to further develop the quality of the existing assays.
  2. We are also continuously testing new technologies available at other SciLifeLab facilities for different types of applications within our platform.
  3. We work together with the other SciLifeLab facilities and make a joint effort to develop technology and adapt this for diagnostic testing. Collaborative work has been carried out with all three NGI facilities in Stockholm and Uppsala.
  4. We also carry out development work in joint collaborative projects with researches at other research organisations.
  5. We work with commercial entities (both global leaders in their respective fields and small-scale startups) to test in early access mode and possibly implement new products. Examples of such activities include work carried out with Illumina, Agilent technologies, Genalice and others. We are also in active dialogue regarding software and analysis based collaborations with several leading analysis solution providers such as Molecular Health, IBM and others.


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.


Eradication of Helicobacter pylori and Gastric Cancer: A Systematic Review and Meta-analysis of Cohort Studies.
Doorakkers E, Lagergren J, Engstrand L, Brusselaers N
J. Natl. Cancer Inst. 2016 Sep;108(9):

Draft Genome Sequence of Streptococcus gordonii Type Strain CCUG 33482T.
Salvà-Serra F, Jakobsson H, Thorell K, Gonzales-Siles L, Hallbäck E, Jaén-Luchoro D, et al
Genome Announc 2016 Mar;4(2):

The 5300-year-old Helicobacter pylori genome of the Iceman.
Maixner F, Krause-Kyora B, Turaev D, Herbig A, Hoopmann M, Hallows J, et al
Science 2016 Jan;351(6269):162-5

Dormant phages of Helicobacter pylori reveal distinct populations in Europe.
Vale F, Vadivelu J, Oleastro M, Breurec S, Engstrand L, Perets T, et al
Sci Rep 2015 Sep;5():14333

Composition of human faecal microbiota in resistance to Campylobacter infection.
Kampmann C, Dicksved J, Engstrand L, Rautelin H
Clin. Microbiol. Infect. 2016 Jan;22(1):61.e1-8

Gut microbiome and innate immune response patterns in IgE-associated eczema.
West C, Rydén P, Lundin D, Engstrand L, Tulic M, Prescott S
Clin. Exp. Allergy 2015 Sep;45(9):1419-29

Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD.
Casén C, Vebø H, Sekelja M, Hegge F, Karlsson M, Ciemniejewska E, et al
Aliment. Pharmacol. Ther. 2015 Jul;42(1):71-83

Intestinal dysbiosis in children with short bowel syndrome is associated with impaired outcome.
Engstrand Lilja H, Wefer H, Nyström N, Finkel Y, Engstrand L
Microbiome 2015 ;3():18

Increase in the Prevalence of Atrophic Gastritis Among Adults Age 35 to 44 Years Old in Northern Sweden Between 1990 and 2009.
Song H, Held M, Sandin S, Rautelin H, Eliasson M, Söderberg S, et al
Clin. Gastroenterol. Hepatol. 2015 Sep;13(9):1592-600.e1

Increase in the Prevalence of Atrophic Gastritis Among Adults Age 35 to 44 Years Old in Northern Sweden Between 1990 and 2009.
Song H, Held M, Sandin S, Rautelin H, Eliasson M, Söderberg S, et al
Clin. Gastroenterol. Hepatol. 2015 Sep;13(9):1592-600.e1

Psoriasis is not an autoimmune disease?
Fry L, Baker B, Powles A, Engstrand L
Exp. Dermatol. 2015 Apr;24(4):241-4

No difference in small bowel microbiota between patients with irritable bowel syndrome and healthy controls.
Dlugosz A, Winckler B, Lundin E, Zakikhany K, Sandström G, Ye W, et al
Sci Rep 2015 Feb;5():8508

Impact of lifestyle on the gut microbiota of healthy infants and their mothers—the ALADDIN birth cohort.
Hesla H, Stenius F, Jäderlund L, Nelson R, Engstrand L, Alm J, et al
FEMS Microbiol. Ecol. 2014 Dec;90(3):791-801

Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden.
Walker M, Talley N, Inganäs L, Engstrand L, Jones M, Nyhlin H, et al
Hum. Pathol. 2015 Feb;46(2):277-83

Susceptibility to Campylobacter infection is associated with the species composition of the human fecal microbiota.
Dicksved J, Ellström P, Engstrand L, Rautelin H
MBio 2014 Sep;5(5):e01212-14

A repetitive DNA element regulates expression of the Helicobacter pylori sialic acid binding adhesin by a rheostat-like mechanism.
Åberg A, Gideonsson P, Vallström A, Olofsson A, Öhman C, Rakhimova L, et al
PLoS Pathog. 2014 Jul;10(7):e1004234

DegePrime, a program for degenerate primer design for broad-taxonomic-range PCR in microbial ecology studies.
Hugerth L, Wefer H, Lundin S, Jakobsson H, Lindberg M, Rodin S, et al
Appl. Environ. Microbiol. 2014 Aug;80(16):5116-23

Low gut microbiota diversity in early infancy precedes asthma at school age.
Abrahamsson T, Jakobsson H, Andersson A, Björkstén B, Engstrand L, Jenmalm M
Clin. Exp. Allergy 2014 Jun;44(6):842-50

Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section.
Jakobsson H, Abrahamsson T, Jenmalm M, Harris K, Quince C, Jernberg C, et al
Gut 2014 Apr;63(4):559-66

The impact of Crohn's disease genes on healthy human gut microbiota: a pilot study.
Quince C, Lundin E, Andreasson A, Greco D, Rafter J, Talley N, et al
Gut 2013 Jun;62(6):952-4

Genome sequencing reveals a phage in Helicobacter pylori.
Lehours P, Vale F, Bjursell M, Melefors O, Advani R, Glavas S, et al
MBio 2011 ;2(6):

Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin.
Fahlén A, Engstrand L, Baker B, Powles A, Fry L
Arch. Dermatol. Res. 2012 Jan;304(1):15-22

A method for metagenomics of Helicobacter pylori from archived formalin-fixed gastric biopsies permitting longitudinal studies of carcinogenic risk.
Zheng Z, Andersson A, Ye W, Nyrén O, Normark S, Engstrand L
PLoS ONE 2011 ;6(10):e26442

The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity.
Basmarke-Wehelie R, Sjölinder H, Jurkowski W, Elofsson A, Arnqvist A, Engstrand L, et al
Gastroenterology 2011 Sep;141(3):918-28

Titration-free 454 sequencing using Y adapters.
Zheng Z, Advani A, Melefors , Glavas S, Nordström H, Ye W, et al
Nat Protoc 2011 Aug;6(9):1367-76

Helicobacter pylori defines local immune response through interaction with dendritic cells.
Andres S, Schmidt H, Mitchell H, Rhen M, Maeurer M, Engstrand L
FEMS Immunol. Med. Microbiol. 2011 Mar;61(2):168-78

A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes.
Willing B, Dicksved J, Halfvarson J, Andersson A, Lucio M, Zheng Z, et al
Gastroenterology 2010 Dec;139(6):1844-1854.e1

Titration-free massively parallel pyrosequencing using trace amounts of starting material.
Zheng Z, Advani A, Melefors O, Glavas S, Nordström H, Ye W, et al
Nucleic Acids Res. 2010 Jul;38(13):e137

Type I restriction-modification loci reveal high allelic diversity in clinical Helicobacter pylori isolates.
Andres S, Skoglund A, Nilsson C, Krabbe M, Björkholm B, Engstrand L
Helicobacter 2010 Apr;15(2):114-25

Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome.
Jakobsson H, Jernberg C, Andersson A, Sjölund-Karlsson M, Jansson J, Engstrand L
PLoS ONE 2010 Mar;5(3):e9836

The cag PAI is intact and functional but HP0521 varies significantly in Helicobacter pylori isolates from Malaysia and Singapore.
Schmidt H, Andres S, Nilsson C, Kovach Z, Kaakoush N, Engstrand L, et al
Eur. J. Clin. Microbiol. Infect. Dis. 2010 Apr;29(4):439-51


Group Members

Anna AndreassonAssistant professor
Emma FranssonSenior research specialist
Fredrik BoulundPostdoc
Hugo WeferBioinformatician
Ina Schuppe KoistinenDirector
Jing WangAssociated
Johanna SiminResearch assistant
Juan DuPostdoc
Lars EngstrandProfessor/senior physician, Associated, Head of office
Luisa Warchavchik HugerthPostdoc
Marica HamstenSenior lab manager
Nele BrusselaersAssistant professor
Saeed ShoaieAssociated

Research engineer

Alexandra Pennhag

Organizational unit: CTMR


Paulo Czarnewski

Organizational unit: Research Group E Villablanca


Associated members


Clinical Genomics members

Head of unit

Valtteri Wirta

Phone: 08-524 815 45
Organizational unit: Clinical Genomics Facility


Robin Andeer

Organizational unit: Clinical Genomics Facility


Emma Sernstad

Organizational unit: Clinical Genomics Facility

Laboratory engineer

Sofie Sibia



Hugo Wefer

Organizational unit: Lars Engstrand group

Research engineer

Cecilia Svensson

Organizational unit: Clinical Genomics Facility

Research engineer

Anna Zetterlund

Organizational unit: Clinical Genomics Facility

Research engineer

Daniel Backman

Organizational unit: Clinical Genomics Facility

Research engineer

Keyvan Elhami

Organizational unit: Clinical Genomics Facility


Kenny Billiau

Organizational unit: Clinical Genomics Facility


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). The Lars Engstrands group is a partner in the Centre for Infectious Disease (CID) research consortium at Karolinska Institutet. Furthermore, Lars Engstrands group is partner in the Centre for Infectious Disease (CID) research consortium at Karolinska Institutet and recently 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
  • Cancerfonden
  • EuroNanoMed
  • Söderbergs stiftelse

Useful links

Washington University, School of Medicin
Baylor College of Medicine


Institutionen för Medicinska Vetenskaper, Uppsala Universitet




Infectious Disease Control