Wednesday, May 15, 2013

Wrap-Up of Cell Symposium on Microbiome and Host Health

For a parasitologist with a major interest in novel technology like me the Cell Symposium on Microbiome and Host Health (#CMHH) was a challenging, yet stimulating tour de force in bacteriology and immunology, and I realise that gut fungi and protists still fly below the radar of intestinal microbiome research.

The announced line-up of speakers was impressive, and although we missed e.g. Drs Peter Turnbaugh and Fergus Shanahan, we were still spoiled with brilliant talks.

Most of the projects and results presented on the meeting were based on studies on bacterial diversity and structure by either targeted 16S 454 sequencing or metagenomics, while studies of gene function and the 'super-organism' that is the complete microbiome (including the  fungome and protistome I should say, since these genomes are much larger than bacterial ones) were still scarce if represented at all.

Since my focus is on intestinal parasites, my main interest in the vast universe of the human microbiome naturally orbits around the intestinal microbiome. Although there is still a long way to go - due to e.g. significant differences in methodologies and lack of consensus on the analytical basis for 'enterotypes'  - we are slowly but steadily building up a picture of the effect that the human microbiome has on health and disease. Hundreds of species live and have important functions in our gut, to cite Dr Peer Bork, but these species have also been associated with more than 30 human diseases, even neurological ones. Shifts in the composition of the microbiome are associated with an expanding list of chronic diseases that includes obesity, inflammatory bowel disease, and diabetes (Dr Ruth Ley).

Many things may influence our susceptibility to intestinal pathogens, including competition between species (colonisation resistance), the ability of some bacteria to synthesise antimicrobial compounds or stimulate innate immune defenses. Differences in susceptibility to infection may boil down to differences in antimicrobial compounds secreted by our individual microbiota (Dr Michael Fischbach). Bacteroides fragilis is a commensal immunoregulatory microbe mediating major effects through a single molecule, polysaccharide A (Dr Dennis Kasper); polysaccharide A mediates immunoregulation via innate and cognate immune system collaboration.

The list of buzz words was endless, and patterns of cause and effect in this fascinating hubbub of cutting edge science difficult to keep apart - but then again, - many pathways and interactions leading to alterations in gut flora and thereby alteration in host clinical phenotype may result from the complex interplay of any type of intervention (diet, antibiotics, surgery (gastric bypass), microbe exposure, etc.) and host genetics. Dr Wendy Garrett used some of her time to address the fact that antibiotic treatment may lead to more significant perturbation of the intestinal microbiota than e.g. diets and immunoregulation, and she also encouraged thoughts on how to approach causality in studies of microbial communities.

Other things that are interesting include how bacteria "talk" together by quorum sensing to control gene expression and crosstalk between beneficial bacteria (e.g. probiotics) and the intestinal ecosystem, and how these systems can be influenced altogether.

Computer technology - the Creed of today: The Barcelona Supercomputing Centre (with 'Mare Nostrum') located in a former chapel. Source.

So, while focus is still on the trillions of bacteria we have in our gut, we hope that it won't be long before common eukaryotic components of the intestinal microbiome will be studied and analysed alongside with bacterial communities. It says on Wikipedia that targeted studies of eukaryotic and viral communities are limited and subject to the challenge of excluding host DNA from amplification and the reduced eukaryotic and viral biomass in the human microbiome. Excluding host DNA is challenging, but not impossible, and who has actually documented that eukaryotic biomass in the human microbiome is 'reduced'?

The meeting was very well organised and took place at the Sheraton Hotel in Lisbon. I've storified a list of the #CMHH tweets here in case you are interested in more 'headlines'. I apologise for any misquotes.

Further reading:

Koren O, Knights D, Gonzalez A, Waldron L, Segata N, Knight R, Huttenhower C, & Ley RE (2013). A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets. PLoS Computational Biology, 9 (1) PMID: 23326225

Andersen LO, Vedel Nielsen H, & Stensvold CR (2013). Waiting for the human intestinal Eukaryotome. The ISME Journal PMID: 23407309

Ivanov II, & Honda K (2012). Intestinal commensal microbes as immune modulators. Cell Host & Microbe, 12 (4), 496-508 PMID: 23084918

Brown J, de Vos WM, Distefano PS, Doré J, Huttenhower C, Knight R, Lawley TD, Raes J, & Turnbaugh P (2013). Translating the human microbiome. Nature Biotechnology, 31 (4), 304-8 PMID: 23563424

Blaser M, Bork P, Fraser C, Knight R, & Wang J (2013). The microbiome explored: recent insights and future challenges. Nature Reviews. Microbiology, 11 (3), 213-7 PMID: 23377500

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