Changes in the gut microbiota have previously been associated with systemic lupus erythematosus (SLE) in humans and in mouse models of the disease, as have changes in the metabolism of tryptophan, which requires microbial involvement. However, a causative link between gut microbiota dysbiosis, tryptophan metabolism and autoimmune disease was lacking. In a new study published in Science Translational Medicine, researchers demonstrated that dysbiotic gut microbiota from lupus-prone mice can initiate autoimmunity in healthy mice and that this disease trigger can be modified by manipulating tryptophan metabolism.

Fecal transfer from B6.Sle1.Sle2.Sle3 lupus-prone mice to control C57BL/6 mice (which are 95% genetically identical to the lupus-prone mice) caused the control mice to develop autoimmunity, but only when the donor lupus-prone mice showed signs of autoimmune disease. However, co-housing of lupus-prone and control mice reduced autoimmunity in the lupus-prone mice but did not generate full-blown autoimmunity in the control mice, suggesting a mitigating effect of horizontal transfer of microbes.

Metabolism of tryptophan in lupus-prone mice was altered compared with control mice and could be restored to normal by antibiotic treatment. In addition, changing the amount of dietary tryptophan available to the mice altered the gut microbiota of both lupus-prone and control mice, indicating a firm link between the gut microbiota and tryptophan metabolism.

Extending this link to autoimmunity, fecal transfer from lupus-prone mice fed a high-tryptophan diet (which worsened their disease) to germ-free control mice induced autoimmunity, whereas fecal transfer from lupus-prone mice fed a low-tryptophan diet (which prevented disease) did not.

Further studies will be necessary to investigate whether gut microbiota dysbiosis and tryptophan metabolism have the same role in patients with SLE.