When the gut microbe Enterococcus gallinarum leaks out of the intestines and sets up camp in other organs such as the liver, it appears to trigger an autoimmune response similar to what's seen in lupus, a new study in mice reveals. In humans, E. gallinarum was detected in the livers of lupus patients but not healthy controls, hinting at a potential cause for this highly mysterious autoimmune disease. While studying mouse models of lupus, Silvio Manfredo Vieira et al. found that treatment with an antibiotic reduced mortality and secretion of lupus-related immune system proteins, suggesting that a type of bacteria may be exacerbating the disease. They fluorescently traced bacteria in the mice, detecting the presence of E. gallinarum in the lymph nodes, liver, and spleen. Intriguingly, they found that E. gallinarum in these organs resulted in increased secretion of immune signals that are associated with autoimmunity in lupus patients, yet the presence of other types of bacteria in these organs did not induce such autoimmunity. In human liver biopsies, they detected the presence of E. gallinarum in samples from lupus patients, but not in healthy controls. As well, many liver samples from patients with autoimmune hepatitis were found to contain E. gallinarum. These results suggest that, if E. gallinarum manages to escape from the gut, it has the potential to trigger disease. In a related Perspective, Sandra Citi highlights this study and a related one, providing more context on the mechanisms behind a leaky gut barrier and potential therapies to improve it. In a different study also evaluating at the gut barrier, Christoph Thaiss et al. find that high blood sugar levels, as seen in diabetes and obesity, are associated with intestinal barrier dysfunction and susceptibility to infection in mice. Preliminary data supports this finding in humans as well, the authors report. Together, these studies highlight the importance of a healthy gut barrier in preventing disease.