NIH Research Festival
The human intestine harbors a microbiome composed of approximately one hundred trillion bacteria from thousands of species, the vast majority of which have an unknown effect on human health. In this investigation, proteomics using shotgun mass spectrometry and transcriptomics using gene microarrays were used to quantitatively compare terminal ilea from conventional and germ-free mice. Female and male mice responded similarly to the microbiome, but C57BL/10A mice responded more strongly than BALB/c mice at both the transcriptome and proteome levels. The microbiome primarily affected two classes of pathways: immunological pathways were down-regulated and metabolic pathways were up-regulated in the germ-free ilea. Most of the affected pathways were only observed at either the transcriptome or proteome level, not both. For example, altered interferon signaling, mitochondrial oxidative phosphorylation, and cholesterol biosynthesis were only detected in the transcriptome. In contrast, altered dopamine, ethanol, histamine, phenylalanine, and tryptophan degradation were only detected at the proteome level. Of the pathways affected at both levels, most were co-regulated (i.e., the gene products were either up-regulated in both or down-regulated in both). Interestingly, differentially regulated pathways were discovered, and these pathways were not principally involved in metabolism or the immune system. Instead they were principally involved in transcription, protein quality control, and protein degradation. A meta-analysis was performed using transcriptomics data from eight previously published reports (all were of conventional versus germ-free mouse intestinal tissue; 243 samples total), and similar transcript-level responses to the microbiome were discovered.
Scientific Focus Area: Systems Biology
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