Gut microbiota-expressed sulfotransferase sulfonates 25-hydroxyvitamin D3 and promotes depression

Vitamin D deficiency (VDD) has been associated with depressive symptoms, but the underlying cause of this deficiency remains unclear. Here, we isolated and cultured Escherichia coli (E. coli) from the feces of depressive patients with VDD and found that this bacterium could metabolize 25-hydroxyvitamin D3 (25[OH]D3) in vitro. In vivo, oral gavage of E. coli induced a decline in circulating 25[OH]D3 levels and elicited depressive-like behaviors in mice. The gene encoding the 25[OH]D3-metabolizing enzyme in E. coli was identified as a sulfotransferase (SULT). A recombinant strain engineered for heterologous expression of SULT similarly reduced serum 25[OH]D3 levels and induced depressive-like behaviors. Interestingly, 25[OH]D3-3-sulfate, the sulfonation product of 25[OH]D3, also produced depressive-like behaviors in mice. Finally, both the prevalence of E. coli and the abundance of the SULT gene were strongly increased in depressive patients when compared to healthy controls. Our findings indicate that SULT expressed by gut microbiota may contribute to depressive symptoms by promoting 25[OH]D3 sulfonation and increasing 25[OH]D3-3-sulfate levels. However, further clinical and mechanistic studies are required to translate these findings to human depression.