Research Unit Microbial Diseases Prevention - Deng Lab
The Deng lab uses an integrative approach combining single-cell technologies, culture-independent techniques, multi-omics, and machine learning to understand the underlying mechanisms of phage-host interactions and their impact on the human host. Ultimately, we aim to develop personalized phage-based treatments against multiple human diseases and conditions.
About our research
The Research Unit Microbial Diseases Prevention focuses on using integrative approaches combining single-cell technologies, culture-independent techniques, multi-omics, and machine learning to understand the underlying mechanisms of phage-host interactions and their impact on the human host.
Gut bacteria are central to human health by regulating multiple functions, producing essential metabolites, and protecting against pathogen invasion. Conversely, changes in their community composition are associated with several diseases and conditions like stunting. Likely, these bacteria are amenable to external perturbations. However, nonspecific changes can cause unpredicted long-term consequences. Bacteriophages or phages' high level of specificity, which reduces the risk of damaging these communities, suggest them as the right tools for safe manipulation of gut bacteria.
We study phage-host interactions to develop novel phage-based therapeutics for i) targeting drug-resistant bacteria and ii) preventing or iii) ameliorating severity in dysbiosis associated diseases and conditions, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), graft versus host disease (GVHD), allergy, and much more by manipulating the human microbiota.
To facilitate the acceptance of phage therapy, which uses phages to target pathogenic bacteria, in Germany, we have developed highly efficient phage cocktails against multiple critical multiresistant bacteria, such as Acinetobacter baumanii, Pseudomonas aeroginosa, Klebsiella pneumonia, and Staphylococcus aureus. In addition, we promote increasing collaborations between scientists and physicians toward defining a roadmap for future translational phage research in Germany.
Most important publications
Thiele Orberg E, Meedt E, Hiergeist A, Xue J, Heinrich P, Ghimire S, Miltiadous O, Lindner S, Schwarz A, Janssen K-P, Herhaus P, Verbeek M, van den Brink MRM, Weber D, Edinger M, Wolff D, Kleigrewe K, Herr W, Bassermann F, Gessner A, Deng L*, Holler E*, Poeck H*
Bacterial and Bacteriophage Consortia are Associated with Protective Intestinal Immuno-modulatory Meta-bolites in Allogeneic Stem Cell Transplantation Patients (5) 187–208. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many blood cancers and disorders. However, its success can be limited by serious complications like graft-versus-host disease (GvHD), where the donor's immune cells attack the patient's body. We know that the gut microbiome—the community of bacteria, fungi, and viruses in our intestines—plays a crucial role in patient outcomes. Gut microbiota produce metabolites that can regulate the immune system and protect the intestinal lining. Yet, exactly how the different members of the microbiome- especially gut bacteriophages- work together to produce these protective compounds has remained unclear. Our latest study aimed to unravel these complex interactions to identify specific microbial signatures linked to better patient health.Key Findings and Impact
In a collaborative study between the Technical University of Munich and the University Hospital Regensburg, our team analyzed the gut bacteriome, virome, and metabolites in 78 patients undergoing allo-SCT. We discovered a specific consortium of bacteria (from the Lachnospiraceae and Oscillospiraceae families) and their associated bacteriophages that was linked to a healthy gut metabolome and better clinical outcomes, including improved survival and lower rates of relapse.
Perhaps the most exciting and novel discovery was the direct contribution of bacteriophages to this protective environment. We identified two temperate bacteriophages that carry a gene called butyryl-CoA: acetate CoA-transferase (BCoAT) as an auxiliary metabolic gene. This gene is essential for producing butyrate, a key short-chain fatty acid known to fuel intestinal cells and reduce inflammation. This finding provides some of the first evidence in humans that bacteriophages can carry metabolic genes to directly augment their bacterial host's functions, a process that benefits the entire ecosystem (Figure 1).
Luo S, Ru J, Khan Mirzaei M, Xue J, Peng X, Ralser A, Hadi JL, Mejías-Luque R, Gerhard M and Deng L*
Helicobacter pylori infection alters gut virome by expanding temperate phages linked to increased risk of colorectal cancer gutjnl-2023-330362. (IF: 31.795)Luo S, Ru J, Khan Mirzaei M, Xue J, Peng X, Ralser A, Mejías-Luque R, Gerhard M and Deng L*
Gut virome profiling identifies an association between temperate phages and colorectal cancer promoted by Helicobacter pylori infection 15(2): 2257291. (IF: 14.4)Ru J, Khan Mirzaei M, Xue J, Peng X and Peng X, and Deng L*
ViroProfiler: a containerized bioinformatics pipeline for viral metagenomic data analysis 15(1): p. 2192522. doi: 10.1080/19490976.2023.2192522.Unterer, M., M.K. Mirzaei, and Deng L*
Targeted Single-Phage Isolation Reveals Phage-Dependent Heterogeneous Infection Dynamics 0(0): p. e05149-22.Tiamani K, Luo S, Schulz S, Xue J, Costa R, Khan Mirzaei M & Deng L*
The role of virome in the gastrointestinal tract and beyond doi:10.1093/femsre/fuac027Khan Mirzaei M, Deng L*
New technologies for developing phage-based tools to manipulate the human microbiome 18:S0966-842X(21)00118-9. doi: 10.1016/j.tim.2021.04.007.Unterer M, Khan Mirzaei M, Deng L*
Gut Phage Database: phage mining in the cave of wonders 17;6(1):193. doi: 10.1038/s41392-021-00615-2.Dzunkova M, Low SJ, Daly JN, Deng L, RinkeC, Hugenholtz P
Defining the human gut host-phage network through single-cell viral tagging 4(12):2192-2203. doi: 10.1038/s41564-019-0526-2Deng L, Ignacio-Espinoza JS, Gregory A, Poulos PT, Weitz JS, Hugenholtz P, Sullivan MB
Viral tagging reveals discrete populations in Synechococcus viral genome sequence space 513, 242-245. doi: 10.1038/nature13459.Publications
Xue, J. ; Ru, J. ; Deng, L.
Phagentherapie durch Hochdurchsatz-Tagging beschleunigen.Wang, X. ; Tian, S. ; Zhang, Y. ; Yang, L. ; Hu, D. ; Wang, Z. ; Yang, X. ; Li, S. ; Wei, J. ; Zhou, W. ; Wang, S. ; Deng, L. ; Li, F. ; Hou, S. ; Li, P. ; Ru, J.
Bacteria and phage consortia modulate cecal SCFA production and host metabolism to enhance feed efficiency in ducks.Yang, L. ; Ru, J. ; Guo, S. ; Yang, X. ; Li, P. ; Deng, L. ; Wang, X.
Research note: The chicken gut virome: Spatiotemporal dynamics and divergent responses to antibiotic versus phytogenic supplementation.