Host-microbe crosstalk
Host-microbiome interaction plays an important role in health and diseases. We believe deciphering this complex crosstalk can open a new window to better understand and treat human diseases. We are interested in the following questions:
(1) What are the molecular mechanisms contributing to the abnormal host-microbiome-immune interactions in inflammatory diseases?
(2) To what extent the obtained mechanistic insights can be translated into human body?
(3) How to steer diseased host-microbiome interactions toward a healthier state?
Miniature gut system
Advanced in vitro gut models are critical for understanding the molecular mechanisms underpinning the gastrointestinal disorders in a humanized and controlled manner. Using a mesofluidic microphysiological system GuMI, we are establishing a multi-cellular co-culture of gut microbes (in isolation or in consortia), intestinal epithelium, and immune cells. The co-culture system aims to recapitulate the complex multi-cellular, inter-species interactions at the mucosal barrier interface, serving as an useful tool for deciphering the molecular crosstalk of microbiota, host, and their environment.
Microbiome engineering
There are increasing evidence on the causal relationship between microbial changes and human diseases. Unlike human genome, human microbiota is much more versatile to modulate. We aims to use microbiome engineering strategies to modify the microbial composition toward designed beneficial functions such as production of specific metabolites, reducing endotoxin levels, and training immune cells. We apply a combination of microbial culture-dependent and independent approaches, together with organoids culture and miniature gut models to design and test the effects of bacterial species in isolation and in consortia. We hope to find the optimal bacterial strains and consortia that have potential to treat diseases and understand the mechanism of actions.
Scientists involved in this project
Jianbo Zhang
Stanley Brul
Hilde Herrema (Amsterdam UMC)
Max Nieuwdorp (Amsterdam UMC)
Wouter de Jonge (Amsterdam UMC)
Aniko Korosi
Publications
- An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii.
Zhang J, Huang YJ, Trapecar M, Wright C, Schneider K, Kemmitt J, Hernandez-Gordillo V, Yoon JY, Poyet M, Alm EJ, Breault DT, Trumper DL, Griffith LG.NPJ Biofilms Microbiomes. 2024 Mar 29;10(1):31. doi: 10.1038/s41522-024-00501-z.PMID: 38553449 Free PMC article.
- Impact of manipulation of glycerol/diol dehydratase activity on intestinal microbiota ecology and metabolism
Ramirez Garcia, A., Zhang, J., Greppi, A., Constancias, F., Wortmann, E., Wandres, M., Hurley, K., Pascual-García, A., Ruscheweyh, H. J., Sturla, S. J., Lacroix, C., & Schwab, C. (2021). Environmental Microbiology, 23(3), 1765-1779. https://doi.org/10.1111/1462-2920.15431
- Coculture of primary human colon monolayer with human gut bacteria.
Zhang, J., Hernandez-Gordillo, V., Trapecar, M., Wright, C., Taketani, M., Schneider, K., Chen, W. L. K., Stas, E., Breault, D. T., Carrier, R. L., Voigt, C. A., & Griffith, L. G. (2021). Nature Protocols, 16(8), 3874-3900. https://doi.org/10.1038/s41596-021-00562-w
- Primary Human Colonic Mucosal Barrier Crosstalk with Super Oxygen-Sensitive Faecalibacterium prausnitzii in Continuous Culture.
Zhang, J., Huang, Y. J., Yoon, J. Y., Kemmitt, J., Wright, C., Schneider, K., Sphabmixay, P., Hernandez-Gordillo, V., Holcomb, S. J., Bhushan, B., Rohatgi, G., Benton, K., Carpenter, D., Kester, J. C., Eng, G., Breault, D. T., Yilmaz, O., Taketani, M., Voigt, C. A., Griffith, L. G. (2021). Med, 2(1), 74-98.e9. https://doi.org/10.1016/j.medj.2020.07.001