Saturday, June 2, 2012

Blastocystis and Microbiomology

Speaking of metagenomics: The July 2012 issue of one of the most prestigious journals in the field of clinical microbiology, Clinical Microbiology and Infection (CMI – published by European Society of Clinical Microbiology and Infectious Diseases), focuses entirely on recent advances in metagenomics, including its implications on clinical microbiology. Several of the keynote speakers from the MetaHIT conference in Paris (March, 2012) have contributed with papers, including Rob Knight, Willem M. de Vos and Paul W. O’Toole. In his editorial, Didier Raoult, puts emphasis on mainly two things: 1) that we need to be patient with data obtained from studies using metagenomics, since currently some conclusions are pointing in different directions and data are still scarce, and 2) that metagenomic studies should be independent of financial support from commercial sources, such as the industry of antibiotics and probiotics.

Although it may be too early to make b/w inferences from data already published, I think that the pioneers in metagenomics teach us to re-think or at least modify several hypotheses about the role of intestinal microbes in gastrointestinal health and disease and pursue new and exciting trajectories. In this blog post I would like to highlight a few things that may be interesting to people who are not familiar with metagenomics, but who are interested in our gut flora and how it may impact our lives.

So, what is metagenomics? Well, only a few years ago, microbiologists were used to looking at one single organism at a time, when exploring the potential role of an organism in health and disease. They were dependent on isolating the organism, for instance by culture, in order to have sufficient material for molecular studies, and in order to avoid mix-up of data from contaminating organisms. However, the human intestinal microbiome (gut flora) is made up by a plethora of organisms, mainly prokaryotes (bacteria), but also to some extent eukaryotes (parasites and fungi), archaea and viruses. Metagenomics, facilitated by massive high-throughput parallel sequencing of nucleic acids extracted from human faecal samples, allows us to get a holistic picture of the entire gut flora of a person. I.e.: We move from examining one single species or organism at a time, to be analysing entire eco-systems. We get to know not only the composition of microbic species inhabiting our gut, but also how they impact our body physiology: Interestingly, Gosalbes et al. (2012) describe how the composition of the intestinal flora may differ significantly from person to person, but later shows that the active intestinal flora is fairly similar among healthy individuals. So, what’s the active flora? Briefly: while metagenomics analyses the DNA (16s rDNA) from the microbiome and hence provides us with data on the mere composition of microbes, including a quantification, metatranscriptomics looks at RNA communities by looking at 16S rRNA and mRNA transcripts. In this way, we get to know the function of the intestinal microbiota and can temporarily ignore the part of the microbial community that is in “stand-by” mode only. The collective genome of the intestinal microbes vastly surpasses the coding capacity of the human genome with more than 3 million genes - in comparison the human genome comprises 20,000-25,000 protein-coding genes.

So far, metagenomic studies have focused mainly on bacteria, and hence we know very little about how intestinal parasites directly or indirectly impact the remaining gut flora and the host, and, importantly, how the bacterial flora influences the presence and activity of parasites. This is due in part to methodological limitations, but mainly to the fact that the bacterial microbiome can be viewed as an organ of the human body (Baquero et al., 2012) taking care of vital and irreplaceable functions that the host is not otherwise capable of, ranging from energy and vitamin metabolism to epithelial barrier integrity and immune modulation (Salonen et al., 2012). Like any other organ, the microbiome has physiology and pathology, and the individual (and collective?) health might be damaged when its collective population structure is altered (Baquero et al, 2012). This is one of the reasons why studies of host-gut flora interactions have focused on bacteria.

One of the striking findings in metagenomic studies is that humans can be more or less successfully stratified into three enterotypes based on their intestinal flora (Arumugam et al., 2011):

We see that the three enterotypes are dominated by mainly three different types of bacteria (Bacteroides, Prevotelia and Ruminocoocus, respectively). However, as mentioned earlier, functional analysis (and probably a lot more sampling) is required to understand microbial communities. One of the interesting topics in this respect is how enterotypes correlate to different health/disease phenotypes; i.e. whether people with a certain gut flora are more prone to (a) certain type(s) of disease(s).There is preliminary evidence that variations in the microbiota are linked to diseases including bowel dysfunction and obesity.

In terms of parasites, I believe that in the near future we will see data revealing to which extent - if any - common intestinal micro-eukaryotes such as Blastocystis and Dientamoeba correlate with these enterotypes or other subsets of bacteria which will enable us to generate hypotheses on the interaction of micro-eukaryotes and the bacterial flora, which in turn may impact host physiology. I will expand a little more on this in an upcoming letter in Trends in Parasitology (article in press).

Interested in more: Why not have a look at Carl Zimmer's article in The New York Times about gut flora transplantation, or read about modulating the intestinal microbiota of older people to promote enhanced nutrition utilisation and to improve general health (O'Toole et al., 2012)... Also, have a look at my most recent blog post.


O’Toole, P. (2012). Changes in the intestinal microbiota from adulthood through to old age Clinical Microbiology and Infection, 18, 44-46 DOI: 10.1111/j.1469-0691.2012.03867.x  

Gosalbes, M., Abellan, J., Durbán, A., Pérez-Cobas, A., Latorre, A., & Moya, A. (2012). Metagenomics of human microbiome: beyond 16s rDNA Clinical Microbiology and Infection, 18, 47-49 DOI: 10.1111/j.1469-0691.2012.03865.x  

Baquero, F., & Nombela, C. (2012). The microbiome as a human organ Clinical Microbiology and Infection, 18, 2-4 DOI: 10.1111/j.1469-0691.2012.03916.x  

Salonen, A., Salojärvi, J., Lahti, L., & de Vos, W. (2012). The adult intestinal core microbiota is determined by analysis depth and health status Clinical Microbiology and Infection, 18, 16-20 DOI: 10.1111/j.1469-0691.2012.03855.x

Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D., Fernandes, G., Tap, J., Bruls, T., Batto, J., Bertalan, M., Borruel, N., Casellas, F., Fernandez, L., Gautier, L., Hansen, T., Hattori, M., Hayashi, T., Kleerebezem, M., Kurokawa, K., Leclerc, M., Levenez, F., Manichanh, C., Nielsen, H., Nielsen, T., Pons, N., Poulain, J., Qin, J., Sicheritz-Ponten, T., Tims, S., Torrents, D., Ugarte, E., Zoetendal, E., JunWang, ., Guarner, F., Pedersen, O., de Vos, W., Brunak, S., Doré, J., Consortium, M., Weissenbach, J., Ehrlich, S., & Bork, P. (2011). Enterotypes of the human gut microbiome Nature, 474 (7353), 666-666 DOI: 10.1038/nature10187

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