Science

1.3 A Dynamic System (3)

As scientists, we know that there is no golden age of health. For every disadvantage that is cited from modern living, there are obvious advantages: more children have asthma, now but more are also living past the age of five years old. Both are products of industrial revolution and modernity. As complex ecosystems, the choices we make as individuals and as a culture come with trade-offs. Some are readily apparent, some we will never know, and some, as in the case of antibiotics, we are only now realizing their full impact on our human holobionts.

Current research into the human ecosystem and specifically that of the gut microbiota is showing just how intricate and individual every human ecosystem is. A whole scientific field of microbial ecology has sprung up to study the human holobiont from The Human Microbiome Project[i]  (HMP) to the crowd-sourced American Gut[ii] study[1].

Currently, for every partial answer we get to these questions, a myriad of new questions sprout, hydra-like, from them as our holobionts assert that they are dynamic systems. Studies of these systems need to take into account the complexity and that we can’t know everything about it.  Often it can get confusing to look at every individual entity in the gut, so scientists sometimes limit themselves to examining a specific aspect of the system (always keeping in mind that this examination is only a partial and fragmented look at the whole). One of these aspects can be what types of microbes live in our gut ecosystems by looking at the bacterial genetic signature: the 16S rRNA[2]. Another aspect can be what active genes are doing. As we will discuss later, organisms are genetic stories that are told about how to best survive in their ecosystem as well as how they’ve changed to survive in the past.  Genes are like the words that make up a narrative about how a single cell functions. A contained narrative in a cell is a book and a collection of books (AKA cells) can be considered a library—sometimes libraries contain diverse books in many languages. Sometimes a library can have a collective focus where each narrative contributes to the others, telling a larger story than in a single book.

The collective genomes or narratives (human, microbial, viral, etc . . .) of a holobiont is called a hologenome; the hologenome is the equivalent of library with a collective focus but instead of the books being static object, each narrative contributes to the structure and function of the library as a whole. Scientists often use metagenomic analysis to study the gut. Metagenomic analysis refers to the study of all genes from various organisms that make up an ecosystem, so it’s like looking at all words in all the books in an entire library at once.  Sometimes that examination can be too broad and we need to narrow our reading of genetic texts. In our case, metagenomics is examination of the total DNA from us as well as the bacteria, yeast, and Archaea (and viruses) that live in and on us, called the microbiome. Through metagenomic analysis of the microbiome, we can look at the aggregate effect of the entire microbial population, not just how one organism functions.  That way we can get an idea of the genetic and metabolic capacity of the community as a whole.  This technique is particularly vital when you realize that microbes (and humans) do not function in a vacuum. Unlike books sitting quietly on shelves[3], cells have a lot of cross-talk among members of their own species, members of other species, and host cells. What we get then, is not the genome of one particular organism, but the genome of the entire community.  This use of “meta-omes” (metagenome—combined gene analysis; metabolome—combined metabolic function analysis; meta-proteome—combined protein analysis) is the acknowledgement that nothing operates in isolation.  Therefore, we can gain more valuable information about function and effect by looking at everything together as best we can rather than looking at something by itself.

Due to advances in metagenomic analysis, we are not only learning more about the ways our human genes work, but also how the myriad of microbes and viruses in our guts contribute to the genetic richness of our human holobiont. Because the goal of every participant in our holobiont is to eat (energy) and have sex (genetic continuance), our holobiont benefits from the metabolic contribution of its parts because every biont in the system has a greater chance to disseminate its genetic material than it would on its own. A holobiont’s metabolism lets each biont participate in a specific niche, consolidating its functional expenditure to a few tasks and letting the larger system provide everything else. Our human holobionts today process nutrient energy the same as other human holobionts have since the dawn of agriculture (with perhaps the notable and very recent advent of the Western diet); and we’ve never changed having sex. The humans who began the agricultural revolution had microbiota that worked in concert with their cells to make the most out of the nutrients available to the ecosystem, therefore, sharing and dividing metabolic role to create a larger system of metabolic functions—the metabolome—that can respond to any stress or change thrust upon it, just as we do today.

[1] The Human Microbiome Project (HMP) maps microbial contributions to the human system’s metabolome.  It looks at types/species of microbes actually present in the human host as well as larger patterns of genes activated for specific metabolic roles. Currently, a worldwide collaboration of researchers is working on the HMP and published its data in multiple journals in 2012, which is the natural progression from the Human Genome Project.  The latter’s purpose was to sequence the entire human genome; the former’s, to sequence and identify functional roles of the entire metagenome within each human that actually constitutes our functional selves.  According to Peter Turnbaugh, the HMP seeks to answer the following questions:
How stable and resilient is an individual’s microbiota throughout one day and during his or her lifespan? How similar are the microbiomes between members of a family or members of a community, or across communities in different environments? Do all humans have an identifiable ‘core’ microbiome, and if so, how is it acquired and transmitted? What affects the genetic diversity of the microbiome, and how does this diversity affect adaptation by the microorganisms and the host to markedly different lifestyles and to various physiological or pathophysiological states? (Turnbaugh 2007)
[2] 16S rRNA is the gene that encodes a component of the ribosomes of microbes, specifically the ribosomal RNA found in the small subunit of the ribosome (our genetic signature is our 18S rRNA).  In the case of the gastrointestinal tract, metagenomics allows us to identify formerly unculturable microbes via sequencing of their 16S rRNA (or in this case rDNA).  From this sequence, we can compare it against a database of known sequences and gain genera/species identification as well as physiology and life processes (some because we assume that physiological traits are conserved among species and others because we can isolate and sequence specific genes and match them up against a database of known genes).
[3] Though we would argue as bibliophiles that books do not sit static: they engage in quite a lot of cross talk.
[i] Peter J. Turnbaugh et al., “The Human Microbiome Project,” Nature 449, no. 7164 (October 18, 2007): 804–10, doi:10.1038/nature06244.
[ii] “American Gut,” Indiegogo, accessed February 17, 2013, http://www.indiegogo.com/projects/322024; “Human Food Project – Anthropology of Microbes,” Human Food Project, accessed February 17, 2013, http://humanfoodproject.com.
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