Creating and characterizing communities of human gut microbes in gnotobiotic mice

Abstract

Microbiology labs are laden with flasks, plates, and freezer stocks containing axenic cultures and their products. In contrast, virtually every other habitat on Earth is filled with microbial communities of varying degrees of complexity. In this context, microorganisms are interdependent components of ecosystems; deciphering this dynamic requires a move from microbial organisms studied in isolation to model microbial communities studied under conditions that mimic those encountered by their members in their native habitats. Here we focus on model communities consisting of microbes that inhabit the human body habitat containing our largest collection of organisms – the gut. The adult human gastrointestinal tract is a microbial bioreactor, containing all three domains of life. This ecosystem is teeming with microorganisms at its distal end (1011-1012 cells/ml luminal contents in the colon) and less so at its proximal end (an estimated 103-104/ml luminal contents in the duodenum). The gut microbiota affects myriad aspects of our systems physiology, ranging from processing and harvesting of macro- and micronutrients (and xenobiotics!) from our diets, to shaping the features of our innate and adaptive immune system. Recently, deep sampling of the fecal microbial community has revealed that each of us harbors a collection of a several hundred bacterial phylotypes (Qin et al., 2010; Turnbaugh et al., 2010). The exact set of microbes differs from person to person although there is a greater degree of similarity between family members (Turnbaugh et al., 2009a; Turnbaugh et al., 2010). A catalogue of several million genes present in the fecal microbiome has been assembled (Qin et al., 2010) from analysis of a 577 Gbp dataset obtained from shotgun sequencing of fecal community DNA prepared from 124 Europeans and a 10.1 Gbp dataset generated from a set of deeply sampled obese monozygotic co-twins living in the USA. These datasets provide a starting point for making in silico predictions about functions that can be attributed to the gut microbiota. Measurements of expressed mRNAs (Turnbaugh et al., 2010), proteins (Verberkmoes et al., 2009) and metabolites (Hoverstad et al., 1984; Li et al., 2008; Martin et al., 2008) in fecal samples represent a first step towards testing these predictions.