associated TP9: The microbiome in disease

Host genome-microbiota interaction and its influence on chronic inflammation in the mouse

Chronic inflammatory diseases result from the interaction of genetic susceptibility factors and environmental factors, broadly defined as infectious, chemical, physical, nutritional, and behavioral factors. While major progress has been made in identifying genetic susceptibility factors, comparatively little is known about environmental risk factors or the forces that lead to variation in genetic susceptibility in nature. Within the body of a healthy individual, microbial cells are estimated to outnumber human cells by a factor of ten to one. Recent advances in the field of metagenomics have begun to define these microbial communities, but knowledge of their influence on immunity, nutrition and susceptibility to disease remains in its infancy. Important questions remain regarding the extent to which the microbiota is influenced by genetic variation in the host genome and whether disease susceptibility may be mediated by the microbiota. Indirect evidence (i.e. cellular fatty acid profiles of the fecal bacteria) suggests a prominent role of host genetic background on the composition of the microbiota, and single gene studies support the notion that the host genome is capable of fostering a communicable, pro-inflammatory microbiota. We hypothesize that naturally occurring variation in the host genome influences the composition of the resident microbiota, and this in turn influences susceptibility to chronic inflammatory diseases. To test this hypothesis we will systematically describe and manipulate the microbiota of genetically distinct mouse inbred strains that differ in susceptibility to chronic inflammatory diseases.

Girish Srinivas graduated in 10/2013 and now works as a PostDoc at the Max-Planck-Institue in Cologne.