This work aims to describe the Brain-Immune system-Gut Triangle (BIG-T) and the possible pathways connecting its constituent systems such that either one can influence the other in addition to the influence of the microbiota on stress and vice versa; the influence of the microbiome and BIG-T on mental illnesses like Mood Disorders, Autism Spectrum Disorders, Schizophrenia, and Alzheimer’s Disease. Possible treatment options capable of manipulating the gut microbiome’s composition and quality in order to alter or improve the mental state are highlighted including probiotics, diet, lifestyle, Ayuverda, helminths, fecal matter transplant (FMT) and antibiotics and current barriers to research and new approaches are raised.