The main findings of this manuscript are: (1) decreased stability of rest-activity (IS) was associated with an aggressive IBD phenotype; (2) increased fragmentation (IV) and decreased amplitude (RA) correlated with markers of subclinical inflammation (intestinal permeability, increased serum cytokine TNF-α, and stool calprotectin); and (3) “pro-inflammatory” changes in microbial structure and function were associated with disruption of rest-activity which are markers of circadian misalignment. Here, TNF is linked to inflammatory bowel disease.