The performance of the human microbiome is perturbed in unknown ways by a variety of factors including disease and diet. Here we aimed to determine the impact of inflammatory bowel disease (IBD) and a resistant starch diet on the gut microbiome community composition and functional potential by application of an array of omics technologies: 16S rRNA sequencing, metagenomics, metaproteomics and metabolomics. The first studies focused on a Swedish twin cohort and a longitudinal cohort for IBD. Specific bacterial species, proteins and metabolites correlated with different sub-phenotypes of the IBD; including a reduced amount of normal beneficial microbes as well as proteins involved in butyrate metabolism, suggesting potential biomarkers of IBD. For the dietary study, subjects transitioned from a baseline diet to one with low or high amounts of resistant starch. Specific bacteria, proteins and metabolites were shown to significantly vary in abundance when comparing baseline to the high resistant starch diet. Together these studies exemplify the use of omics to provide potential bioindicators of specific physiological states of importance to human health.