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MRC Toxicology Unit

 

Unit Programme: Microbiome mediated toxicity of drugs and other xenobiotics

Director of Research: Dr Kiran Patil

An adult individual typically harbours a few hundred grams of bacteria in their digestive tract. Recent findings have brought forward the fundamental role of this microbiota in determining drug efficacy, mode of action and side effects. Yet, such interactions at the microbiome level remain unknown for the vast majority of the drugs and for other xenobiotics that we are exposed to (e.g. food contaminants like pesticides). The overarching goal of Kiran’s research programme is to discover and model complex (xeno-) metabolic networks emerging in the gut microbiota and thereby gain mechanistic insights into microbiome-mediated toxicity. To this end, this interdisciplinary programme brings together computational (metabolic modelling, bioinformatics, chemo-informatics and machine learning) and experimental (in vitro microbiomics, metabolomics and chemical genomics) approaches.

Key publications:

1. Machado D, Andrejev S, Tramontano M, Patil KR. Fast automated reconstruction of genome-scale metabolic models for microbial species and communities. Nucleic Acids Research. doi: 10.1093/nar/gky537 (2018)

2. Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, Brochado AR, Fernandez KC, Dose H, Mori H, Patil KR, Bork P, Typas A. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. doi: 10.1038/nature25979 (2018)

3. Tramontano M, Andrejev S, Pruteanu M, Klünemann M, Kuhn M, Galardini M, Jouhten P, Zelezniak A, Zeller G, Bork P, Typas A, Patil KR. Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies. Nature Microbiol. doi: 10.1038/s41564-018-0123-9 (2018)

4. Ponomarova O, Gabrielli N, Sévin DC, Mülleder M, Zirngibl K, Bulyha K, Andrejev S, Kafkia E, Typas A, Sauer U, Ralser M, Patil KR. Yeast Creates a Niche for Symbiotic Lactic Acid Bacteria through Nitrogen Overflow. Cell Systems. DOI: 10.1016/j.cels.2017.09.002 (2017)

5. Zelezniak A, Andrejev S, Ponomarova O, Mende DR, Bork P & Patil KR. Metabolic dependencies drive species co-occurrence in diverse microbial communities. Proc. Natl. Acad. Sci. U.S.A. 112 (20), 6449-6454 (2015).