Funding from the research council!
I am very happy to share the news that our starting grant application to the Swedish Research Council has been granted 3.3 million SEK of funding for four years! This is fantastic news, as it allows us to further explore the interactions between bacteria in the human microbiome that are important for community stability and resilience to being colonized by pathogens. In the granted project, we will investigate environmental and genetic factors that are important for bacterial invasiveness and community stability in the human gastrointestinal tract.
Within the scope of the project, we will establish model bacterial communities and experimental systems for the human stomach and intestine. We will then investigate how disturbances, such as antibiotic exposure, change the interactions in these microbial communities and their long-term stability. Finally, we aim to identify genes that contribute to successful bacterial colonization or resilience to invasion of established communities in the human microbiome.
Aside from myself, Prof. Sara Lindén and Dr. Kaisa Thorell from the University of Gothenburg as well as Prof. Ed Moore at the university’s Culture Collection will be involved in this project in different ways. We will also collaborate with my former postdoc supervisor Prof. Jo Handelsman as well as Dr. Ophelia Venturelli at the University of Wisconsin-Madison. Finally, we will also collaborate with Dr. Åsa Sjöling at the Karolinska Institute. I look forward to work with you all over the coming four years! A big thanks to the Swedish Research Council for believing in this research and investing in making it happen!
Bug hunting in the Metaxa2 beta
Due to an extremely embarrassing for-loop error in the classifier of the most recent Metaxa2 beta (beta 8), which was released a few weeks ago, the classifier often would (on certain platforms and configurations) enter an endless loop and hang. I apologize for this mistake, which has been corrected in the new beta 9 released today, available from this download link. No other changes have been made since the previous version. Thanks for your patience (and thanks Kaisa Thorell for first bringing my attention the error!)
Published paper: Helicobacter pylori vs. the viable gastric microbiota
I have just returned from a week of vacation in Sicily (almost without internet access), so I am a tad late to this news, but earlier this week Infection and Immunity published our paper on the Helicobacter pylori transcriptome in gastric infection (and early stages of carcinogenesis), and how that relates to the transcriptionally active microbiota in the stomach environment (1). This paper has been long in the making (an earlier version of it was included in Kaisa Thorell’s PhD thesis (2)), but some late additional analyses did substantially strengthen our confidence in the suggestions we got from the original data.
In the paper (1) we use metatranscriptomic RNAseq to investigate the composition of the viable microbial community, and at the same time study H. pylori gene expression in stomach biopsies. The biopsies were sampled from individuals with different degrees of H. pylori infection and/or pre-malignant tissue changes. We found that H. pylori completely dominates the microbiota in infected individuals, but (somewhat surprisingly) also in the majority of individuals classified as H. pylori uninfected using traditional methods. This confirms previous reports that have detected minute quantities of H. pylori also in presumably uninfected individuals (3-6), and raises the question of how large part of the human population (if any) that is truly not infected/colonized by H. pylori. The abundance of H. pylori was correlated with the abundance of Campylobacter, Deinococcus, and Sulfurospirillum. It is unclear, however, if these genera only share the same habitat preferences as Helicobacter, or if they are specifically promoted by the presence of H. pylori (or tissue changes induced by it). We also found that genes involved in pH regulation and nickel transport were highly expressed in H. pylori, regardless of disease stage. As far as we know, this study is the first to use metatranscriptomics to study the viable microbiota of the human stomach, and we think that this is a promising approach for future studies on pathogen-microbiota interactions. The paper (in unedited format) can be read here.
- Thorell K, Bengtsson-Palme J, Liu OH, Gonzales RVP, Nookaew I, Rabeneck L, Paszat L, Graham DY, Nielsen J, Lundin SB, Sjöling Å: In vivo analysis of the viable microbiota and Helicobacter pylori transcriptome in gastric infection and early stages of carcinogenesis. Infection and Immunity, accepted manuscript (2017). doi: 10.1128/IAI.00031-17 [Paper link]
- Thorell K: Multi-level characterization of host and pathogen in Helicobacter pylori-associated gastric carcinogenesis. Doctoral thesis, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg (2014). [Link]
- Bik EM, Eckburg PB, Gill SR, Nelson KE, Purdom EA, Francois F, Perez-Perez G, Blaser MJ, Reman DA: Molecular analysis of the bacterial microbiota in the human stomach. PNAS, 103:732-737 (2006).
- Dicksved J, Lindberg M, Rosenquist M, Enroth H, Jansson JK, Engstrand L: Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls. Journal of Medical Microbiology, 58:509-516 (2009).
- Maldonado-Contreras A, Goldfarb KC, Godoy-Vitorino F, Karaoz U, Contreras M, Blaser MJ, Brodie EL, Dominguez-Bello MG: Structure of the human gastric bacterial community in relation to Helicobacter pylori status. ISME Journal, 5:574-579 (2011).
- Li TH, Qin Y, Sham PC, Lau KS, Chu KM, Leung WK: Alterations in Gastric Microbiota After H. Pylori Eradication and in Different Histological Stages of Gastric Carcinogenesis. Scientific Reports, 7:44935 (2017).