Café com Física



14 de outubro de 2015

Michael S. Gilmore
Harvard Medical School

MERDA – the fingerprint of life history: Disentangling a previously incomprehensible multiple particle system (or) Inferring the health of Schrödinger's cat from its litter box

The principle is well established in particle physics that, intrinsic in every particle, is information that is influenced by the physical nature of the particle, as well as its history. In a multi-particle system, every particle represents an information-rich entity that contributes in some definable way to the properties of the entire system. This same lens can be used to view microbes that inhabit the human body. All environmentally exposed surfaces of animals are saturated with microbes. The gut houses the vast majority (about 1014) of microbes associated with humans, because it is rich in the elements that support microbial life - high water and nutritional content. Like physical particles, each microbe in the gut ecosystem possesses information – there is a history as to how it got there, it has specific properties that are allowing it to stay and even proliferate there, etc.. Microbes of the gut are not a random assemblage. There are about 1000 different abundant microbial species in the typical gut, and many more species occurring in low numbers along the very long tail of the decay curve descending from 1014. Many of the most abundant microbes in the gut are initially aquired when the largely sterile baby transits the birth canal. Other usually rarer microbes derive from the diet, transmission between individuals, and the environment. Some may become long time residents of the gut, and others may just pass through. Since bacteria have the ability to replicate in the gut, the relative representation of a particular type of bacterium is defined by properties including metabolic capabilities of that microbe, and their compatibility with the environmental conditions within the gut. Environmental conditions within the gut are determined by such factors as diet, supportive or antagonistic factors produced by other resident microbes, and supportive and antagonistic factors secreted into the gut by the host. Host determinants of the microbial population composition and structure include rate of mucous secretion, rate of secretion of antimicrobial defense factors in the mucous, pH changes along the length of the gut, glucose and other nutrient content of the host secretions into the gut, temperature, water content, and many other factors. Factors that influence what the host secretes into the gut include age and state of development of the host immune system, sex of the host, diseases of the host (e.g., gut inflammation, diabetes, cystic fibrosis, etc.), relative activity of the host, and other factors that affect gut contraction rates and transit time. Other factors that influence the population structure within the gut include the rate of nutrient consumption by the host in relationship to the ability of that host to digest and absorb the nutritional content, such that excess consumption leads to a surplus of nutrients in the gut available to the microbial community. The main point is that the composition of gut microbes is highly unique to each person or animal, and depends on the specific properties of both the microbe as well as the host. Each microbe within the population conveys information about the history of the animal (such as the identity of its mother), about its diet and rate of consumption/over consumption, about its health, about its history of antibiotic use or intestinal disease, and many other traits. That is, gut flora are a highly specific historic and metabolic fingerprint of each animal. With the development of “Next Generation” DNA sequencing, we now have the ability to identify and enumerate about 99.9999% of the microbes in the gut of each animal. Based on a growing body of data, we are just beginning to develop the bioinformatic tools and rules necessary to correlate the microbial content of the gut with health. In the near future, analysis of gut flora (feces) will be a relatively painless and rapid means for comprehensively understanding the health and natural history of humans and animals. The objective is to reach a point where we understand the information content of each of the 1014 particles that constitute the human gut community.