Dr. Melanie Schirmer (Broad Institute of MIT and Harvard)
Biological Colloquium of the Christian-Albrechts-University Kiel
Monday, 2nd September 2019, 4:30 pm
Center for Molecular Biosciences (ZMB)
Seminar room 4th floor
Am Botanischen Garten 11
As guest of the CRC 1182
Computational Scientist at the Broad Institute of MIT and Harvard working in the groups of Ramnik Xavier and Curtis Huttenhower
The intestinal microbiome: Integrated multi’omics analyses elucidate host-microbial interactions
The gut microbiome plays a critical role in human health and immune-related diseases. However, the underlying mechanism of host-microbial interactions remain largely unknown. In order to understand the role of the microbiome in disease, we need to identify changes in the gut microbiome at disease onset and monitor patients longitudinally. Using baseline and longitudinal follow-up samples from 405 pediatric, new-onset, treatment-naive ulcerative colitis patients, we showed that compositional and temporal changes in the gut microbiome are linked to disease course, including disease severity and progression. Furthermore, integrated multi-omics approaches allow us to understand the functional consequences of disease-related taxonomic changes and enable us to investigate how these microbial changes potentially affect the host. Using paired metagenomic and metatranscriptomic data from the integrative Human Microbiome Project (iHMP) we identified species-specific biases in transcriptional activity and showed that disease-specific microbial characteristics can be more pronounced or only detectable at the transcript level, such as pathways predominantly expressed by different organisms in IBD patients (e.g. Bacteroides vulgatus and Alistipes putredinis). In order to understand how microbial changes can affect the host, we further linked microbial factors to aberrant immune responses in healthy individuals and identified microbially derived mediators that influence immune phenotypes in response to common microorganisms. Overall, these studies highlight that moving from census to function can provide important insights into the role of the microbiome in human health.
Schirmer M, Denson L, Vlamakis H, Franzosa EA, Thomas S, Gotman NM, Rufo P, Baker SS, Sauer C, Markowitz J, Pfefferkorn M, Oliva-Hemker M, Rosh J, Otley A, Boyle B, Mack D, Baldassano R, Keljo D, LeLeiko N, Heyman M, Griffiths A, Patel AS, Noe J, Kugathasan S, Walters T, Huttenhower C, Hyams J, Xavier RJ.
Cell Host Microbe. 2018 Oct 10;24(4):600-610.e4. doi: 10.1016/j.chom.2018.09.009. PMID: 30308161
Schirmer M, Franzosa EA, Lloyd-Price J, McIver LJ, Schwager R, Poon TW, Ananthakrishnan AN, Andrews E, Barron G, Lake K, Prasad M, Sauk J, Stevens B, Wilson RG, Braun J, Denson LA, Kugathasan S, McGovern DPB, Vlamakis H, Xavier RJ, Huttenhower C.
Nat Microbiol. 2018 Mar;3(3):337-346. doi: 10.1038/s41564-017-0089-z. Epub 2018 Jan 8. PMID: 29311644
Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, Horst RT, Jansen T, Jacobs L, Bonder MJ, Kurilshikov A, Fu J, Joosten LAB, Zhernakova A, Huttenhower C, Wijmenga C, Netea MG, Xavier RJ.
Cell. 2016 Dec 15;167(7):1897. doi: 10.1016/j.cell.2016.11.046. No abstract available. PMID: 27984736