Mice with wild microbiomes predict clinical results

NIH's National Institute of Diabetes and Digestive and Kidney Diseases created a laboratory mouse model with a wild microbiome that could yield better predictions of clinical results than conventional lab mice. The mice, dubbed "wildlings," were created by transplanting embryos from lab mice into surrogates captured in farmhouses. The wildlings had gut, skin and vaginal microbiomes more similar to those of wild than conventional lab mice. Wildlings treated with an agonist mAb targeting CD28 induced production of proinflammatory cytokines, while conventional lab mice had more anti-inflammatory Treg cells in the spleen and higher serum levels of anti-inflammatory cytokine IL-10 -- replicating results observed in a Phase I trial of CD28 agonist TGN1412 from TeGenero Immuno Therapeutics AG. Similarly mirroring a clinical result, mortality rose in wildlings modeling septic shock after treatment with Amgen Inc.'s Enbrel etanercept (see "Lab Mice With 'Wild' Microbiomes Better Reflect Clinical Data")...