Perilipin-2 modulates dietary fat-induced microbial global gene expression profiles in the mouse intestine

Intestinal microbiota are critical determinants of obesity and metabolic disease risk. In previous work we showed that deletion of the cytoplasmic lipid droplet (CLD) protein Perilipin-2 (Plin2) modulates gut microbial community structure and abrogates long-term deleterious effects of a high fat (HF) diet in mice. However the impact of Plin2 on microbiome function is unknown. Here we used metatranscriptomics to identify differences in microbiome transcript expression in WT and Plin2-null mice following acute exposure to high or low fat diets. Consistent with previous studies, dietary changes resulted in significant taxonomic shifts. Unexpectedly, when fed a HF diet, the microbiota of Plin2-null and WT mice exhibited dramatic shifts in transcript expression despite no discernible shift in community structure. For Plin2-null mice, these changes included the coordinated upregulation of metabolic enzymes directing flux towards the production of growth metabolites. Our data shows that host-genotype can modulate microbiome function without impacting community structure.