One common consequence of infection and inflammation is wasting of skeletal muscle and fat tissue. Now, a new study shows that gut colonization with the O21:H+ commensal strain of Escherichia coli can prevent wasting in a mouse model of intestinal inflammation or in mice infected with Salmonella enterica subsp. enterica serovar Typhimurium or Burkholderia thailandensis. Protection mediated by E. coli O21:H+ required bacterial translocation to the white adipose tissue (WAT) following infection or intestinal inflammation. In the WAT, E. coli O21:H+ induced high levels of insulin-like growth factor 1 (IGF1), in a process that was dependent on activation of the NLRC4 inflammasome. The high levels of IGF1 then stimulated the IGF1–phosphatidylinositol 3-kinase (PI3K)–AKT pathway in skeletal muscle, preventing muscle loss.