The mutually antagonistic relationship between cell-mediated and humoral immunity was first noted in the 1970s21 and was subsequently attributed to the Th1/Th2 axis,22,23 as was the hygiene hypothesis in immune-mediated disease.24 CD8 T cell responses skew immunity away from humoral and towards cellular immunity—our study is the first to examine such responses to the intestinal microbiota in humans and points towards novel strategies in IBD treatment. Here, CD8A is linked to inflammatory bowel disease.