Ecophysiological insights into the human intestinal microbiota: from single strains to defined consortia

Understanding the role of the microbiome in defining and tipping the balance between health and disease can greatly benefit from studies such as those described in this thesis that approach the intestinal microbiome at three levels of complexity, ranging from ecosystems to defined mixed consortia and individual bacterial species. At ecosystem level, we reviewed and identified adult intestinal core microbiota, and discussed the key concepts of the human intestinal microbiome landscape. We further investigated the property of hyperdominance in a broad range of different microbiomes, and hypothesized that niche-neutral processes likely explain the hyperdominance and dynamics of a few well-adapted species in the human intestinal microbiome. We developed an R based software tool package to facilitate open and reproducible data analysis in particular of marker gene sequencing for novice users. Moving further from ecosystem-level to ecophysiological level, we integrated data obtained using multiple complementary techniques to have a better understanding of two key intestinal bacteria, namely Intestinimonas butyricproducens and Eubacterium hallii. We reclassified the two strains of Eubacterium as members of a new genus, Anaerobutyricum, with the strain DSM3353T as the type species A. hallii, and strain L2-7 as novel species named Anaerobutyricum soehngenii. We further carried out a detailed ecophysiological study of A. soehngenii using genomics, proteomics and in-vitro testing of substrate preferences. This led to identification of a unique gene cluster involved in DL- lactate utilization unique to Anaerobutyricum species among the butyrate producers in the human intestinal tract. Next, we used an ecophysiology guided design of a representative human intestinal minimal microbiome. When grown in mixed cultures, the diet based minimal microbiome (Db-MM) community assembly and structure was shaped by the combination of available dietary carbohydrates. The Db-MM designed here is a crucial step towards developing a functionally and phylogenetically diverse and experimentally accessible representation of the human intestinal tract microbiome. Finally, I discuss the observations presented in this thesis and provide potential implications of these findings for human intestinal microbiome research and how they advance our quest for improving the quality of life.