The gut microbiome, an ecosystem of over a trillion micro-organsims that inhabit the human intestine, has become an exciting area of study over the last few years with evidence suggesting effects on body functions and diseases such as maintenance of weight, development of autoimmune diseases, and diabetes. The microbiome is affected by diet, the people you live with, and can be affected by the introduction of bacteria through the ingestion of probiotics. Preclinical studies show that altering the microbiome can affect the integrity of the hypothalamic–pituitary–adrenal (HPA) axis, and possibly increase tryptophan, a precursor of serotonin, the neurotransmitter that increases with the use of SSRIs. This meta-analysis of clinical studies shows a possible positive effect of probiotics on symptoms of depression and anxiety, and, while the data are early in development, they are intriguing and promising, given the safety of probiotics. —Neil Skolnik, MD