High dimensional microbiome interactions shape the host fitness landscape

Koch’s postulates established the field of infectious disease on the concept of one pathogen, one disease. Here we show that interactions between gut bacteria are as important as the bacteria themselves in determining fly physiology. We performed a complete combinatorial dissection of the fly gut microbiome using germ free flies colonized with each possible combination of the 5 core species of bacteria, forming a 5 dimensional cube. We then measured the microbial community abundances and fly fitness traits, including (i) development, (ii) reproduction, and (iii) aging. Notably, microbial diversity accelerates development, reproduction, and aging. From these measurements we calculated the impact of microbial interactions on fly fitness as the triangulations of the 5-cube, following the combinatorial geometry approach of Beerenwinkel-Pachter-Sturmfels. Single species cannot predict pairs, contradicting Koch’s postulates, and higher order interactions are widely prevalent. Important for evolution, we find a positive feedback between the microbial community and host fitness that poises a population for divergence of hosts and the emergence of host-specific microbiomes.